natriuretic-peptide--brain and Chronic-Disease

Chronic heart failure (CHF) is a common and difficult-to-treat disease in clinical practice. The efficacy and safety of Zhenyuan capsule (ZYC) in the treatment of CHF were evaluated by meta-analysis and trial sequential analysis (TSA) of published relevant data.. Searched 8 databases for clinical literature on ZYC in the treatment of CHF, up to December 2022. Then the meta-analysis and TSA were performed on the studies that met the inclusion criteria.. Meta-analysis showed that compared with conventional treatment, combined use of ZYC could significantly increase the clinical effective rate (risk ratio 1.20, 95% confidence interval [CI] 1.14~1.26, P < .00001) by 20%, left ventricular ejection fraction (MD 8.85, 95%CI 4.57~13.12, P < .0001) by 8.85%, and 6-minutes walking distance (MD 47.91, 95%CI 18.66~77.17, P = .001) by 47.91 m, and significantly reduce brain natriuretic peptide (MD -247.86, 95%CI -330.62~-165.09, P < .00001) by 247.86 pg/mL. TSA showed that the benefits suggested by the original results were conclusive. In terms of safety, the total adverse events in the combined group of ZYC were comparable to those in the conventional group, and TSA demonstrated that this result needed more research and demonstration.. ZYC can effectively improve the clinical efficacy of treating CHF, significantly increase left ventricular ejection fraction and 6-minute walk distance, and remarkably reduce brain natriuretic peptide. ZYC, with definite efficacy and safety, has the value of clinical application and in-depth research.

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension and is associated with increased maternal and perinatal morbidity compared with preeclampsia alone. Distinguishing superimposed preeclampsia from chronic hypertension can be challenging because, in chronic hypertension, the traditional criteria for the diagnosis of preeclampsia, hypertension, and significant proteinuria can often predate the pregnancy. Furthermore, the prevalence of superimposed preeclampsia is unlikely to be uniformly distributed across this high-risk group but is related to the severity of preexisting endothelial dysfunction. This has led to interest in identifying biomarkers that could help in screening and diagnosis of superimposed preeclampsia and in the stratification of risk in women with chronic hypertension. Elevated levels of uric acid and suppression of other renal biomarkers, such as the renin-angiotensin aldosterone system, have been demonstrated in women with superimposed preeclampsia but perform only modestly in its prediction. In addition, central to the pathogenesis of preeclampsia is a tendency toward an antiangiogenic state thought to be triggered by an impaired placenta and, ultimately, contributing to the endothelial dysfunction pathognomonic of the disease. In the general obstetrical population, angiogenic factors, such as soluble fms-like tyrosine kinase-1 and placental growth factor, have shown promise in the prediction of preeclampsia. However, soluble fms-like tyrosine kinase-1 and placental growth factor are impaired in women with chronic hypertension irrespective of whether they develop superimposed preeclampsia. Therefore, the differences in levels are less discriminatory in the prediction of superimposed preeclampsia compared with the general obstetrical population. Alternative biomarkers to the angiogenic and renal factors include those of endothelial dysfunction. A characteristic of both preeclampsia and chronic hypertension is an exaggerated systemic inflammatory response causing or augmenting endothelial dysfunction. Thus, proinflammatory mediators, such as tumor necrosis factor-α, interleukin-6, cell adhesion molecules, and endothelin, have been investigated for their role in the screening and diagnosis of superimposed preeclampsia in women with chronic hypertension. To date, the existing limited evidence suggests that the differences between those who develop superimposed preeclampsia and those who do not a

Topics: Aldosterone; Angiogenic Proteins; Biomarkers; Chronic Disease; Cytokines; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Renin; Ultrasonography, Doppler; Uric Acid; Uterine Artery

The initial and dynamic levels of B-type natriuretic peptide (BNP) and N-terminal-prohormone BNP (NT-proBNP) are routinely used in clinical practice to identify patients with acute and chronic heart failure. In addition, BNP/NT-proBNP levels might be useful for risk stratification in patients with and without heart failure. We performed a meta-analysis to investigate, whether the value of BNP/NT-proBNP as predictors of long-term prognosis differentiates in cohorts with and without heart failure.. We systematically searched established scientific databases for studies evaluating the prognostic value of BNP or NT-proBNP. Random effect models were constructed. Data from 66 studies with overall 83 846 patients (38 studies with 46 099 patients with heart failure and 28 studies with 37 747 patients without heart failure) were included. In the analysis of the log-transformed BNP/NT-proBNP levels, an increase in natriuretic peptides by one standard deviation was associated with a 1.7-fold higher MACE rate (hazard ratio [95% confidence interval]: 1.74[1.58-1.91], P < 0.0001). The effect sizes were comparable, with a substantial overlap in the confidence intervals, when comparing studies involving patients with and without heart failure (1.75[1.54-2.0], P < 0.0001 vs. 1.74[1.47-2.06], P < 0.0001). Similar results were observed when stratifying by quartiles of BNP/NT-proBNP. In studies using pre-defined cut-off-values for BNP/NT-proBNP, elevated levels were associated with the long-term prognosis, independent of the specific cut-off value used.. BNP/NT-proBNP levels are predictors for adverse long-term outcome in patients with and without known heart failure. Further research is necessary to establish appropriate thresholds, especially in non-heart failure cohorts.

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis

Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF.. Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale.. Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15-1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17-1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05-3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60-1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23-1.56), and in lowering down the TCM syndrome scores (SMD = -0.78, 95% CI -0.91 to -0.64), Minnesota Living with Heart Failure questionnaire (SMD = -1.01, 95% CI -1.56 to -0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28-0.89), B-type natriuretic peptide (SMD = -0.89, 95% CI -1.52 to -0.25), NT-proBNP (SMD = -2.07, 95% CI -3.34 to -0.08), and C-reactive protein (SMD = -2.04, 95% CI -4.12 to -0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E' between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were "low" and "very low" according to the GRADE assessment.. YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.

Topics: C-Reactive Protein; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

Despite evidence for beneficial effects of Qishen Yiqi Drop Pill (QSYQ) on congestive heart failure, the majority of studies are based on insufficient sample sizes. The aim of this study was to evaluate the therapeutic effects of QSYQ using a meta-analysis approach.. Our current meta-analysis indicated that QSYQ combined with Western therapy might be effective in CHF patients. Further researches are needed to identify which subgroups of CHF patients will benefit most and what kind of combination medicines work best.

Topics: Biomarkers; Chronic Disease; Drugs, Chinese Herbal; Exercise Tolerance; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Recovery of Function; Stroke Volume; Treatment Outcome; Ventricular Function, Left

The underlying mechanism for clinical and biochemical manifestations of chronic heart failure (HF) may be due in part to neurohumoral adaptations, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems in the periphery and the brain. Internet search and discussion with colleagues are the methods for this study. Since chronic HF is associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, it may be considered a brain disease. This phenomenon may be the result of an increased systemic and cerebral angiotensin II signaling because plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic HF. Activation of angiotensin II signaling in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM), and area postrema (AP) may increase the release of norepinephrine, oxidative stress, and inflammation leading to increased cardiac contractility. It is possible that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. The administration of an angiotensin receptor blocker by injection into the AP activates the sympatho-inhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity. In chronic HF, in peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity. Increased circulating angiotensin II during chronic HF may enhance the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in worsening of HF. Increased circulating angiotensin II signaling can directly act on the central nervous system via the subfornical organ and the AP to increase sympathetic outflow resulting in to neurohumoral dysfunction, resulting in to heart failure.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Baroreflex; Brain; Cardiomegaly; Chronic Disease; Heart; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Neuroimmunomodulation; Norepinephrine; Oxidative Stress; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Renin-Angiotensin System; Sympathetic Nervous System; Vagus Nerve Stimulation

In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis.. hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Troponin T

Biomarkers play a fundamental role in the management of heart failure. Both new and old biomarkers are evaluated every year with new information gained for their use in heart failure. Major advancements have been made in the past 2 years in key biomarkers that will surely become part of standard clinical management of heart failure. This review will focus on major developments since 2016.. Soluble suppression of tumorigenicity 2 has had multiple breakthrough studies solidifying its prognostic use in both acute and chronic heart failure and with multiple studies showing a strong benefit with serial monitoring. High-sensitivity troponin has also recently been demonstrated to be a powerful prognostic biomarker in heart failure. Additionally, it may serve as a novel screening tool to identify patients at high risk for incident heart failure. Natriuretic peptides continue to show their resilience as the main prognostic biomarker in heart failure. Recent studies suggest natriuretic peptides may help identify certain patient populations that benefit from specific therapies and they can predict prognosis beyond in diseases other than heart failure.. Although natriuretic peptides are well-established biomarkers in heart failure, the weight of evidence for soluble suppression of tumorigenicity 2 and high-sensitivity troponin has significantly grown since 2016 that these two biomarkers should be incorporated into regular practice and management of heart failure patients.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Troponin

Qishenyiqi dripping pill for chronic heart failure (CHF) remains controversial due to lack of high-quality trials. Therefore, we conduct this pooled-analysis to evaluate the efficacy and safety of Qishenyiqi in CHF patients.. We searched for randomized clinical trials for Qishenyiqi dripping pill in treating CHF up to August 2018 through China National Knowledge Infrastructure (CNKI), the PubMed Database, the Wanfang Database, the China Scientific Journal Database (VIP), and the Chinese Biomedicine Literature Service System. RevMan 5.3 was used for pooled analyses. Based on the New York Heart Association (NYHA) classification, the clinical therapeutic effect was collected as the primary endpoint.. The efficacy and safety of Qishenyiqi combined with routine treatment significantly increased NYHA functional classification, left ventricular ejection fraction, cardiac index, and 6-minute walking test and decreased brain natriuretic peptide, left ventricular end-diastolic, and end-systolic dimensions with no obvious side effects in comparison with routine therapy alone.. Together these results provide important insights into Qishenyiqi is effective and safe in improving ventricular remodeling and function of CHF patients.. PROSPERO106695.

Topics: Cardiovascular Agents; Chronic Disease; Drugs, Chinese Herbal; Heart Failure; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Ventricular Function, Left; Ventricular Remodeling

Pulmonary hypertension has emerged as a major cause of morbidity and mortality in patients with hemoglobinopathies and chronic hemolytic anemias. These hematological diseases include - but are not limited to - sickle cell disease (SCD), thalassemia, paroxysmal nocturnal hematuria, and hereditary spherocytosis. Although most studies have been based on the use of echocardiography as a screening tool for pulmonary hypertension as opposed to the gold standard of right heart catheterization for definitive diagnosis, the association between chronic hemolytic anemia and pulmonary hypertension is evident. Studies have shown that patients with SCD and a tricuspid regurgitant velocity (TRV) ≥ 2.5 m/sec are at increased risk of pulmonary hypertension and are at increased mortality risk. Additional markers of risk of pulmonary hypertension and increased mortality include a pro-BNP >160 pg/mL combined with a 6-min walk distance of <333 m. There is currently a lack of concrete data to support the use of targeted oral pulmonary arterial hypertension therapy in chronic hemolytic anemia. As a result, management is generally targeted towards medical optimization of the underlying anemia. This literature review aims to discuss the pathophysiology, diagnostic and prognostic tools, recent studies and current protocols that are essential in guiding management of pulmonary hypertension in chronic hemolytic anemias.

Topics: Anemia, Hemolytic; Anemia, Sickle Cell; Cardiac Catheterization; Chronic Disease; Echocardiography; Exercise Tolerance; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Walk Test

Chronic heart failure (HF) is a relevant and growing public health problem. Although the prognosis has recently improved, it remains a lethal disease, with a mortality that equals or exceeds that of many malignancies. Furthermore, chronic HF is costly, representing a large and growing drain on healthcare resources.. This narrative review is based on the material searched for and obtained via PubMed up to May 2017. The search terms we used were as follows: "heart failure, echocardiography, natriuretic peptides" in combination with "treatment, biomarkers, guidelines.". Recent studies have supported the value of natriuretic peptides (NPs) and Doppler echocardiographic biomarkers of increased left ventricular (LV) filling pressures or pulmonary congestion as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of pulsed-wave tissue and blood flow Doppler with NPs appears valuable in guiding HF management in the outpatient setting. In as much as both the echo and the plasma levels of NPs may reflect the presence of fluid overload and elevations of LV filling pressures, integrating NP and echocardiographic biomarkers with clinical findings may help the cardiologist to identify high-risk patients, that is to recognize whether a patient is stable or the condition is likely to evolve into decompensated HF, to optimize treatment, to improve the prognosis and to reduce rehospitalization.. We discussed the rationale and the clinical significance of combining follow-up echo and NP assessment to guide management of ambulatory patients with chronic HF.

Topics: Ambulatory Care; Biomarkers; Chronic Disease; Clinical Decision-Making; Echocardiography; Echocardiography, Doppler; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Edema; Ventricular Dysfunction, Left

Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls. Several major factors may account for the reduced effectiveness of the natriuretic peptide system (NPS) in CHF. First, there is reduced availability of active forms of NPs, namely BNP. Second, target organ responsiveness becomes diminished. Third, the counter-regulatory hormones of the RAAS and SNS, and endothelin-1 become over-activated. Therefore, pharmacological approaches to enhance the functional effectiveness of the NPS in CHF have been explored in recent years. In terms of clinical outcomes, studies of synthetic BNP, or of neprilysin inhibitors alone or associated with an angiotensin converting enzyme inhibitor, have been controversial for several reasons. Recently, however, encouraging results have been obtained with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan. The available data show that treatment with sacubitril/valsartan is associated with increased levels of NPs and their intracellular mediator cyclic guanosine monophosphate, suggesting improved functional effectiveness of the NPS, in addition to beneficial effects on mortality and morbidity outcomes. Therefore, combined targeting of the NPS and RAAS with sacubitril/valsartan emerges as the current optimal approach for redressing the neurohormonal imbalance in CHF.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Biphenyl Compounds; Chronic Disease; Drug Combinations; Endothelin-1; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Neprilysin; Receptors, Atrial Natriuretic Factor; Renin-Angiotensin System; Sympathetic Nervous System; Tetrazoles; Valsartan

In recent years, there has been growing evidence that vitamin D deficiency is associated with the development and progression of chronic heart failure (CHF).. Additional supplementation of vitamin D may have protective effects in patients with CHF.. We searched PubMed, Embase, and Cochrane databases through June 2015 and included 7 randomized controlled trials that investigated the effects of vitamin D on cardiovascular outcomes in patients with CHF. Then, we performed a meta-analysis of clinical trials to confirm whether vitamin D supplementation is beneficial in CHF patients. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using fixed- or random-effects models.. Our pooled results indicated that additional supplementation of vitamin D was not superior to conventional treatment in terms of left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and 6-minute walk distance. Moreover, vitamin D supplementation was associated with significant decreases in the levels of tumor necrosis factor-α (WMD: -2.42 pg/mL, 95% CI: -4.26 to -0.57, P < 0.05), C-reactive protein (WMD: -0.72 mg/L, 95% CI: -1.42 to -0.02, P < 0.05), and parathyroid hormone (WMD: -13.44 pg/mL, 95% CI: -21.22 to -5.67, P < 0.05).. Vitamin D supplementation may decrease serum levels of parathyroid hormone and inflammatory mediators in CHF patients, whereas it has no beneficial effects on improvement of left ventricular function and exercise tolerance.

Topics: C-Reactive Protein; Chi-Square Distribution; Chronic Disease; Dietary Supplements; Exercise Tolerance; Heart Failure; Humans; Inflammation Mediators; Natriuretic Peptide, Brain; Parathyroid Hormone; Peptide Fragments; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Stroke Volume; Treatment Outcome; Tumor Necrosis Factor-alpha; Ventricular Function, Left; Vitamin D; Vitamin D Deficiency

This review provides background on the laboratory design for MESA (Multi-Ethnic Study of Atherosclerosis) as well as the approach used in MESA to select biomarkers for measurement. The research related to the multitude of circulating and urinary biomarkers of inflammation and other novel and emerging biological pathways in MESA is summarized by domain, or pathway, represented by the biomarker. The contributions of MESA biomarkers to our knowledge of these key pathways in the development and progression of atherosclerosis, cardiovascular disease, diabetes, kidney disease, and pulmonary disease are highlighted, as are the contributions of MESA to recommendations for clinical use of several of these biomarkers. In addition, contributions of MESA to multicohort genomics consortia and current collaborations in transomics and metabolomics are noted.

Topics: Acute Kidney Injury; Adipokines; Algorithms; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Chronic Disease; Endothelium, Vascular; Fatty Acids; Fibrinolysis; Gonadal Steroid Hormones; Homeostasis; Humans; Infections; Insulin Resistance; Lipid Metabolism; Lymphocytes; Minerals; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Plaque, Atherosclerotic; Renin-Angiotensin System; Risk Assessment; Risk Factors; Troponin T; Vitamins

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Positive-Pressure Respiration; Stroke Volume

The role of B-type natriuretic peptide (BNP) in the management of patients with chronic heart failure (CHF) was uncertain. The aim of this meta-analysis was to comprehensively evaluate the effect of BNP-guided therapy in CHF. Relevant randomized controlled trials were identified by searching of Pubmed, Embase and the Cochrane Library databases. Fixed or randomized effect models were applied to combine the data according to the heterogeneity of the included studies. Fourteen studies with 3,004 CHF patients were included. Results of our meta-analyses suggested that compared with clinical group, BNP-guided treatment significantly decreased the risk of heart failure-related hospitalization (RR 0.79, 95 % CI 0.63-0.98, p = 0.03), although did not significantly affect the risk of all-cause mortality (RR 0.94, 95 % CI 0.81-1.08, p = 0.39) or all-cause hospitalization (RR 0.97, 95 % CI 0.89-1.07, p = 0.56). Furthermore, between-group BNP changes seemed to be a significant modifier to the effects of BNP-guided therapy on clinical outcomes, and BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. In addition, BNP-guided therapy was not associated with increased risk for serious adverse events. BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. BNP-guided therapy seemed to be safe and promising for CHF patients, and future studies with well-designed BNP-guided medication up-titration strategies are needed to confirm these results.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Publication Bias; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome

Cardiac natriuretic peptides (BNP, NT-proBNP) play a pivotal role in cardiovascular homeostasis, mainly due to their roles in vasodilatation, natriuresis, diuresis and due to their antiproliferative properties. Proper measurement of the natriuretic peptide levels may help differentiate between respiratory and cardiac forms of dyspnea, diagnose early forms of heart failure, evaluate severity of heart failure (prognosis) and monitor the efficacy of therapy. In many countries natriuretic peptide levels are being used as one of the earliest diagnostics tools to evaluate the involvement of the heart. Current theoretical and clinical data confirm the importance of natriuretic peptides in routine healthcare. These roles are clearly described in international recommendations and guidelines. In the current review the authors discuss the problems of the measurement of natriuretic peptides in Hungary, including several aspects related to laboratory medicine, cardiology and health economy.

Topics: Acute Disease; Ambulatory Care; Biomarkers; Blood Chemical Analysis; Chronic Disease; Diagnosis, Differential; Direct Service Costs; Dyspnea; Heart Failure; Humans; Hungary; Natriuretic Peptide, Brain; Natriuretic Peptides; Patient Admission; Patient Discharge; Peptide Fragments; Prognosis; Reagent Kits, Diagnostic; Respiratory Tract Diseases; Severity of Illness Index; Treatment Outcome

It has been asserted that serial measurements of natriuretic peptides, specifically B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), may serve as an objective practical guide to better tailor the drug treatment for patients with chronic heart failure (CHF), and especially to detect the cases of subclinical congestion that would require an increase in drug dosing. However, considerable uncertainty remains about the alleged useful role of natriuretic peptide-guided therapy in this context. Therefore, we decided to execute a meta-analysis of published randomized controlled trials (RCTs) to test the hypothesis that an improvement of clinical outcomes in outpatients with CHF may be achieved by adjustment of pharmacologic dosing performed according to natriuretic peptide determinations.. The relevant studies were collected through a search across the PubMed database (January 1996 to September 2012). For our meta-analysis, parallel-group RCTs were eligible for inclusion if they met the following criteria: they enrolled patients with CHF, they randomized patients to a strategy of titrating drug therapy based on the level of a circulating natriuretic peptide (BNP or NT-proBNP) compared to a parallel control group treated according to the clinical conventional criteria, and they reported all-cause mortality. In addition, it was established that each RCT to be incorporated in the evaluation should have included more than 60 participants and its follow-up should have been longer than 90 days. The primary endpoint of the meta-analysis was all-cause mortality and hospitalization related to heart failure (combined endpoint).. In the six pooled RCTs subjected to final meta-analysis (total of included patients = 1775), natriuretic peptide-guided therapy for outpatients with CHF was shown to be associated with a decreased risk of death and heart failure hospitalizations during follow-up (odds ratio - random effect model: 0.64; 95% confidence interval: 0.43-0.95; P = 0.026).. This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

Topics: Ambulatory Care; Biomarkers; Cardiovascular Agents; Chronic Disease; Drug Dosage Calculations; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Outpatients; Predictive Value of Tests; Time Factors; Treatment Outcome

Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality.. Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF.. Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chronic Disease; Drug Substitution; Female; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Ventricular Dysfunction, Left

The goal of this study was to explore the association between changes in B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels and risk of hospital admission for heart failure (HF) worsening in patients with chronic HF.. The relationship between BNP and NT-proBNP plasma levels and risk of cardiovascular events in patients with chronic HF has been previously demonstrated. However, it is unclear whether changes in BNP and NT-proBNP levels predict morbidity in patients with chronic HF.. The MEDLINE, Cochrane, ISI Web of Science, and SCOPUS databases were searched for papers about HF treatment up to August 2013. Randomized trials enrolling patients with systolic HF, assessing BNP and/or NT-proBNP at baseline and at end of follow-up, and reporting hospital stay for HF were included in the analysis. Meta-regression analysis was performed to test the relationship between BNP and NT-proBNP changes and the clinical endpoint. Sensitivity analysis was performed to assess the influence of baseline variables on results. Egger's linear regression was used to assess publication bias.. Nineteen trials enrolling 12,891 participants were included. The median follow-up was 9.5 months (interquartile range: 6 to 18 months), and 22% of patients were women. Active treatments significantly reduced the risk of hospital stay for HF worsening. In meta-regression analysis, changes in BNP and NT-proBNP were significantly associated with risk of hospital stay for HF worsening. Results were confirmed by using sensitivity analysis. No publication bias was detected.. In patients with HF, reduction of BNP or NT-proBNP levels was associated with reduced risk of hospital stay for HF worsening.

Topics: Aged; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Whether additional benefit can be achieved with the use of trimetazidine (TMZ) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of TMZ treatment in CHF patients.. We searched PubMed, EMBASE, and Cochrane databases through October 2013 and included 19 RCTs involving 994 CHF patients who underwent TMZ or placebo treatment. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models.. TMZ therapy was associated with considerable improvement in left ventricular ejection fraction (WMD: 7.29%, 95% CI: 6.49 to 8.09, p<0.01) and New York Heart Association classification (WMD: -0.55, 95% CI: -0.81 to -0.28, p<0.01). Moreover, treatment with TMZ also resulted in significant decrease in left ventricular end-systolic volume (WMD: -17.09 ml, 95% CI: -20.15 to -14.04, p<0.01), left ventricular end-diastolic volume (WMD: -11.24 ml, 95% CI: -14.06 to -8.42, p<0.01), hospitalization for cardiac causes (RR: 0.43, 95% CI: 0.21 to 0.91, p = 0.03), B-type natriuretic peptide (BNP; WMD: -157.08 pg/ml, 95% CI: -176.55 to -137.62, p<0.01) and C-reactive protein (CRP; WMD: -1.86 mg/l, 95% CI: -2.81 to -0.90, p<0.01). However, there were no significant differences in exercise duration and all-cause mortality between patients treated with TMZ and placebo.. TMZ treatment in CHF patients may improve clinical symptoms and cardiac function, reduce hospitalization for cardiac causes, and decrease serum levels of BNP and CRP.

Topics: C-Reactive Protein; Chronic Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; PubMed; Randomized Controlled Trials as Topic; Stroke Volume; Trimetazidine; Vasodilator Agents

Galectin 3 is a protein secreted by activated macrophages and has a role in development of fibrosis in injured tissues. Experimental studies showed increased galectin 3 secretion in the context of cardiac hypertrophy and heart failure models. Several clinical studies identified galectin 3 to be a biomarker of cardiovascular diseases in the field of diagnosis, risk stratification, monitoring therapy response and predicting short-term and long-term prognosis. Particularly, the additional prognostic information of galectin 3 as assessed together with NT-proBNP was established in acute and chronic heart failure.

Topics: Biomarkers; Chronic Disease; Galectin 3; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Pulmonary hypertension is frequent in advanced chronic respiratory diseases, with an estimated prevalence at the time of pulmonary transplantation of 30-50 % in idiopathic pulmonary fibrosis, 30-50 % in chronic obstructive pulmonary disease, 50 % in combined pulmonary fibrosis and emphysema, 75 % in sarcoidosis, and more than 75 % of cases in pulmonary Langerhans cell histiocytosis. Histologic features include varying degrees of pulmonary arterial remodeling (prominent), vascular rarefaction (emphysema), fibrosis or specific involvement of the pulmonary arteries (idiopathic pulmonary fibrosis, sarcoidosis, lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis), in situ thrombosis, and frequently associated involvement of the pulmonary veins (idiopathic pulmonary fibrosis, sarcoidosis). Pulmonary hypertension is usually detected using echocardiography with Doppler, however right heart catheterisation is required to confirm precapillary pulmonary hypertension defined by pulmonary artery pressure ≥ 25 mm Hg, with pulmonary artery wedge pressure ≤ 15 mm Hg. When present, it is associated with decreased exercise capacity and worse mortality. Pulmonary hypertension in chronic respiratory disease is almost invariably multifactorial; hypoxia is one of its main determinants, however supplemental oxygen therapy rarely reverses pulmonary hypertension. Management of pulmonary hypertension in chronic respiratory disease is mostly based on the optimal treatment of the underlying disease. Available data do not support the use of drug therapies specific for pulmonary hypertension in the setting of chronic respiratory diseases, however very few clinical studies have been conducted so far specifically in this context.

Topics: Antihypertensive Agents; Biomarkers; Cardiac Catheterization; Chronic Disease; Dyspnea; Echocardiography, Doppler; Exercise Tolerance; Humans; Hypertension, Pulmonary; Lung Transplantation; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Prognosis; Respiratory Tract Diseases; Severity of Illness Index; Vascular Resistance; Vasodilator Agents

The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF.. MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.509 to 1.035; p = 0.077). [corrected].. Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.

Topics: Age Factors; Aged; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Randomized Controlled Trials as Topic; Treatment Outcome

The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomised controlled trials (RCTs). However, the benefits have been variable. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on all-cause mortality and HF rehospitalisation in patients with chronic HF.. We identified RCTs by systematic search of MEDLINE, EMBASE and the Cochrane Controlled Clinical Trials Register Database. Eligible RCTs were those that enrolled more than 40 patients and involved comparison of BNP-guided versus guideline-guided drug therapy of the patients with chronic HF in the outpatient setting.. Eleven RCTs with a total of 2414 patients and with a mean duration of 12 months (range, 3-36 months) were included in the meta-analysis. Overall, there was a significantly decreased risk of all-cause mortality (relative risk [RR], 0.83; 95% confidence interval [CI], 0.69-0.99; P=0.035; I(2)=0%) and HF rehospitalisation (RR, 0.75; 95% CI, 0.62-0.91; P=0.004; I(2)=62.2%) in the BNP-guided therapy group. Age, baseline BNP are the major dominants of HF rehospitalisation when analysed using meta-regression. In the subgroup analysis, HF rehospitalisation was significantly decreased in the patients younger than 70 years (RR, 0.45; 95% CI, 0.33-0.61; P=0.000; I(2)=0.0%), or with baseline higher BNP (≥2114pg/mL) (RR, 0.53; 95% CI, 0.39-0.72; P=0.000; I(2)=21.8%).. Compared with usual clinical care, B-type natriuretic peptide-guided therapy reduces all-cause mortality and HF rehospitalisation, especially in patients younger than 70 years or with higher baseline BNP.

Topics: Age Factors; Aged; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Male; MEDLINE; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

Reducing readmissions after hospitalisation for acute heart failure is the new challenge of these diseases, approaching 30% within 60 to 90 days of discharge. Congestion related to high ventricular filling pressures, reflected by the high levels of natriuretic peptides, is the main reason for heart failure readmission. Natriuretic peptide levels are a patent prognostic marker of cardiovascular event in chronic heart failure. Treshold values of BNP and NT-proBNP being respectively 125 and 1000 pg/mL. Optimizing treatment of heart failure by monitoring natriuretic peptides, including management of diuretic doses, remains matter of controversies.

Topics: Chronic Disease; Diagnostic Techniques, Cardiovascular; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests

Plasma B-type cardiac natriuretic peptides reflect cardiac structure and function and have proven roles in assisting in the diagnosis of acute heart failure. They are independent prognostic indicators across the full spectrum of cardiovascular disease. Serial changes in plasma B-type cardiac natriuretic peptides parallel prognosis in chronic heart failure. Beneficial responses to medications and devices used in the treatment of heart failure are associated with decreases in plasma B-type peptide concentrations. This effect has led to the hypothesis that intensified treatment directed at reducing B-peptide concentrations may improve outcomes in heart failure.. The efficacy of serial measurements of plasma B-type peptides in guiding titration of therapy for chronic heart failure has been the subject of several randomized controlled trials reported in the peer-reviewed literature since 2000. These reports are summarized in this review. Trial design, characteristics of the heart-failure population studied, duration of follow-up, exact end points recorded, and target peptide concentrations pursued all differ somewhat between trials. In addition, in studies in which benefits were seen, the exact mechanisms mediating the improvements in outcome were unclear. However, an overall consistency is emerging that is supported by 2 metaanalyses.. In aggregate the existing trial data suggest that adjustment of treatment in chronic heart failure according to serial B-type peptide measurements, used in conjunction with established clinical methods, is likely to reduce cardiac mortality and hospital admissions with heart failure, at least in patients with systolic heart failure who are younger than 75 years and relatively free of comorbidities.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Randomized Controlled Trials as Topic

Epidemiologic, clinical, and basic research has identified several antecedent conditions that predispose individuals to heart failure and its predecessor, asymptomatic left ventricular remodeling and dysfunction (stage B heart failure). Many biochemical markers have been described that characterize the remodeling process and the development of cardiac dysfunction. Although natriuretic peptides and cardiac troponin are currently used in the context of diagnosis, risk stratification, and management of stage C and D heart failure, many other biomarkers provide insights into the underlying pathophysiology of left ventricular dysfunction, suggesting new directions for fundamental research or the development of new therapies.

Topics: Biomarkers; Chronic Disease; Disease Progression; Extracellular Matrix; Heart Failure; Humans; Lipid Peroxidation; Microscopy, Electron, Scanning; Natriuretic Peptide, Brain; Oxidative Stress; Peroxynitrous Acid; Tissue Inhibitor of Metalloproteinase-1; Troponin; Ventricular Dysfunction, Left

Circulating biomarkers have become increasingly important in diagnosing and risk-stratifying patients with heart failure (HF). While the natriuretic peptides have received much focus in the past decade, there is increasing interest in the role of other circulating biomarkers such as mid-regional proadrenomedullin (MR-proADM), a stable peptide of the precursor of adrenomedullin (ADM), responsible for volume regulation and electrolyte homeostasis. Increased levels of MR-proADM are associated with an increased risk of mortality and morbidity in patients with HF, independent of natriuretic peptides. MR-proADM outperforms all other established markers in the identification of patients at highest risk of death, particularly death within 30 days. The prognostic superiority has consistently been shown for various cardiovascular disease states, including acute heart failure. In this article, we discuss the potential role of MR-proADM in the syndrome of acute heart failure and its implication on prognosis and risk stratification.

Topics: Acute Coronary Syndrome; Acute Disease; Adrenomedullin; Biomarkers; Chronic Disease; Endothelium, Vascular; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Vasodilation

Chronic cardiac insufficiency manifests itself in a number of clinical syndromes with signs and symptoms characterized by low specificity and sensitivity. ESC and ACC/AHA experts propose to use brain natriuretic peptide (BNP) and/or N-terminal BNP propeptide (NT-proBNP) levels in combination with tissue velocity imaging (TVI) to facilitate diagnostics of this condition. BNP and NT-proBNP levels are highly specific and sensitive indicators of left ventricular myocardium overload while TVI reveals chronic cardiac insufficiency in the asymptomatic phase of its development. Q-analysis of TVI provides data on global and local myocardial contraction and relaxation and allows objective quantitative evaluation of these functions in lieu of less accurate subjective characteristic. A number of cohort studies have confirmed high specificity and sensitivity of TVI, BNP and NT-proBNP levels at the early stages of chronic cardiac insufficiency.

Topics: Chronic Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography

Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Cardiac Resynchronization Therapy; Cardiomyopathies; Chronic Disease; Diagnostic Imaging; Heart Failure; Humans; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain

For patients presenting with acute dyspnea, an incorrect diagnosis could increase the mortality risk. When used in the evaluation of patients with acute symptoms, brain natriuretic peptide and N-terminal pro-brain natriuretic peptide (BNP and NT-proBNP, respectively) testing is highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure (HF). It has been demonstrated that BNP and proBNP levels can facilitate diagnosis and guide HF therapy. Natriuretic peptide (NP) levels are strictly related with HF severity; they are particularly increased in more advanced New York Heart Association (NYHA) classes and in patients with poor outcome. Therefore elevated NP levels were found to correlate with the severity of left ventricular systolic dysfunction, right ventricular dysfunction and pressures, and left ventricular filling alterations. However, the optimal use of NP determination agrees with patient history, physical examination, and all other diagnostic tools. There are some clinical conditions (ie, obesity, renal insufficiency anemia) for which the NP measurement is not diagnostic. Algorithm building taking into consideration all clinical and echocardiographic parameters, as well as NP measurements, may lead to the earlier identification and better risk stratification of patients with chronic HF, independently from etiology.

Topics: Algorithms; Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Severity of Illness Index; Ultrasonography; Up-Regulation; Ventricular Function, Left; Ventricular Function, Right

In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pulmonary and peripheral vascular beds. In patients with moderate to severe forms of CHF, TNF-alpha leads to the formation of nitrotyrosine and consumption of nitric oxide by virtue of activation of myeloperoxidase. Further studies are required to better elucidate the complex interaction of oxidative stress, endothelial dysfunction and inflammatory activation in CHF. Such insights would likely lead to development of better strategies for the assessment of the disease severity by monitoring of new bio-humoral indices and better treatment approaches.

Topics: Biomarkers; Chronic Disease; Endothelium, Vascular; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitrosation; Oxidative Stress; Peroxidase

Topics: Anemia; Biomarkers; Chronic Disease; Creatinine; Diagnosis, Differential; Heart Failure; Hemoglobins; Humans; Kidney; Natriuretic Peptide, Brain; Natriuretic Peptides; Predictive Value of Tests; Prognosis; Renin-Angiotensin System; Risk Factors; Sodium; Uric Acid

Plasma levels of brain natriuretic peptide (BNP) and its inactive fragment N-terminal pro-BNP are recognized as reliable markers of ventricular dysfunction in adults. We aimed to verify BNP applications in children.. A review of the literature on this subject was carried out.. When dealing with paediatric patients, age and sex-related normal values must be considered. Higher BNP plasma levels are reported in children with chronic heart failure; they are related with the type of dysfunction and with prognosis. Moreover, increased BNP levels have been reported in asymptomatic children and adolescents pretreated with anthracyclines, who are at risk for ventricular dysfunction.. BNP and pro-BNP also seem to be effective markers of ventricular dysfunction in paediatric patients. Clinical use may be extended not only for the characterization of heart dysfunction, but also for monitoring asymptomatic patients at specific risk. To this purpose, wider application in clinical trials appears warranted.

Topics: Adolescent; Age Factors; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Child; Chronic Disease; Female; Heart Defects, Congenital; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reference Values; Risk Factors; Sex Factors; Ventricular Dysfunction

BNP or NT-proBNP testing has dramatically changed the management of acute heart failure patients by aiding in early recognition, prognostication and treatment. Furthermore, recent studies have shown that natriuretic peptide testing may guide the therapy of the stable chronic heart failure patients in out-patient setting. We will review the understanding of utilizing natriuretic peptide testing to guide heart failure therapy, including present and future directions for this exciting area.

Topics: Acute Disease; Biomarkers; Chronic Disease; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis

Circulating levels of the BNP system can help in the diagnosis of cardiovascular disease and provide prognostic information not only for patients who have HF but also for the general population and other patient groups. Changes over time also carry prognostic information, and studies are assessing BNP-guided treatment strategies. With the identification of circulating molecular forms of BNP, new insights regarding the biology of the BNP system are emerging that may improve the diagnostic and prognostic value of BNP. Likewise, accounting for rs198389 (a common single nucleotide polymorphism that increases BNP levels) may help to further refine the use of components of the BNP system as biomarkers.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis; Time Factors

Measurement of circulating natriuretic peptides has been shown to play an important role in diagnosis and prognosis in patients with chronic heart failure. Whether serial natriuretic peptide measurements to aid in the titration of therapy can improve heart failure outcomes remains uncertain. We performed a quantitative meta-analysis of available randomized controlled trials to determine whether titration of therapy based on natriuretic peptide measurements improves mortality in chronic heart failure.. We identified potentially relevant studies through a search of MEDLINE (1996-2009), ISI Web of Knowledge (1996-2009), Cochrane Central Register of Controlled Trials (1996-2009), clinicaltrials.gov, proceedings of major US and European cardiology meetings (2000-2009), and bibliographic review of secondary sources. Search terms were "biomarker," "natriuretic peptide," "B-type natriuretic peptide," "N-terminal B-type natriuretic peptide," and "heart failure." Studies were included if they were prospective, randomized controlled trials of patients with chronic heart failure, they randomized patients to a strategy of titrating medical therapy based on the level of a circulating biomarker compared to a parallel control group, and they reported all-cause mortality.. Six studies randomizing 1627 patients met criteria for inclusion. Pooled analysis showed a significant mortality advantage for biomarker-guided therapy (hazard ratio was 0.69, 95% CI 0.55-0.86) compared to control. There was no quantitative evidence of heterogeneity between studies (P = .42).. Titration of therapy incorporating serial BNP or N-terminal pro-B-type natriuretic peptide levels is associated with a significant reduction in all-cause mortality compared to usual care in patients with chronic heart failure.

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Randomized Controlled Trials as Topic

measurement of plasma natriuretic peptide levels has been proposed as a simple, accessible test to assist the diagnosis of cardiac dysfunction and heart failure. Most studies have been hospital based and have investigated the relationship between natriuretic peptides and cardiac dysfunction or heart failure in younger populations.. we performed a systematic review to evaluate the diagnostic accuracy of plasma natriuretic peptide measurement in elderly patients from the general population.. electronic searches of MEDLINE and EMBASE from January 1985 to May 2008 were performed. Diagnostic cohort and cross-sectional studies on the accuracy of natriuretic peptides for diagnosis of cardiac dysfunction or chronic heart failure in people aged 75 and over in the community were included. The quality of the selected studies was assessed with the modified QUADAS tool and the data extracted by two independent reviewers.. five studies were included. The general quality of the studies was moderate. The extracted data could not be pooled. Negative likelihood ratios for cardiac dysfunction ranged from 0.09 to 0.29.. we found limited evidence supporting the use of plasma natriuretic peptide measurement for diagnosis of cardiac dysfunction or heart failure in the elderly of 75 years and over in the general population. Important questions about the implementation of plasma natriuretic peptide measurement in daily practice remain unresolved.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Geriatric Assessment; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Reproducibility of Results; Ventricular Dysfunction, Left

It is known that prognosis of pulmonary hypertension (PH), especially connective tissue disease related PH (CTD-PH), is serious. CTD-PH is caused by not only pulmonary arterial hypertension, but also interstitial pneumonitis, hypoxia, chronic thromboembolism of pulmonary artery, or left heart diseases. Recently, prognosis of PH is improved by progress of diagnostic measures including echocardiography and development of effective vasodilators. However, early diagnosis of PH is necessary for further improvement of the prognosis. Previous reports have shown that diffusion lung capacity for carbon monoxide (DLco) is reduced in the early phase of PH, and we have shown that serum lactate dehydrogenase level is also elevated in this phase. Furthermore, we have been studying significance of stress echocardiography. Therefore, if reduced DLco or LDH elevation are recognized, follow up of laboratory data such as blood levels of KL-6, NT-proBNP, D-dimer, echocardiography, high resolution CT of the lung, in addition to clinical findings are important for prediction of PH.

Topics: Biomarkers; Carbon Monoxide; Chronic Disease; Connective Tissue Diseases; Early Diagnosis; Echocardiography; Humans; Hypertension, Pulmonary; L-Lactate Dehydrogenase; Lung; Lung Diseases, Interstitial; Lung Volume Measurements; Mucin-1; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Embolism; Tomography, X-Ray Computed

Recently, N-terminal pro-B-type natriuretic peptide (NT-proBNP), a new biomarker of cardiac function and heart failure, has become available as a clinical laboratory test in Japan. Its diagnostic and prognostic utility appears to be equivalent to BNP in the clinical setting; however, there are some biologic differences between NT-proBNP and BNP. Unlike BNP, NT-proBNP is not degraded in the circulation, and is stable even in serum. It has a longer half-life of approximately 1 to 2 hours, leading to higher circulating levels and slower fluctuations than BNP. Both of these biomarkers are influenced by renal function, but the effect is greater for NT-proBNP. Recently, NT-proBNP has become an important diagnostic tool for assessing patients who present acutely with dyspnea, and provides important prognostic information in both acute and chronic heart failure. Also, monitoring NT-proBNP levels in the outpatient setting is expected to improve patient care and outcomes. Furthermore, a recent study has reported that NT-proBNP may be independently associated with future cardiovascular events in a large community-based cohort free of heart failure. However, NT-proBNP is affected primarily by renal function, gender, age, and obesity, which should be considered when interpreting values.

Topics: Age Factors; Biomarkers; Chronic Disease; Female; Half-Life; Heart Failure; Heart Function Tests; Humans; Kidney Diseases; Male; Mass Screening; Membrane Proteins; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reference Values; Tumor Suppressor Proteins

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Severity of Illness Index

Natriuretic peptides (NPs) secreted by the heart in response to volume overload are pleiotropic molecules with vasodilating, diuretic, natriuretic, antiproliferative, and antifibrotic actions. Functioning of the NP system is altered in congestive heart failure (CHF), suggesting that support of the NP system might be beneficial in treatment of acute and chronic CHF. Several approaches alone or in combination with other pharmacologic therapies have been shown to enhance function of the NP system: direct administration of native and designer NPs, inhibition of degradation of NPs and their second messenger (cyclic guanosine monophosphate ), and stimulation of cGMP generation. Despite increasing numbers of studies using NPs in therapy of acute and chronic CHF, several controversies regarding safety, efficacy, and dosing of NPs need to be addressed. Moreover, further research is warranted to identify the stages and etiologies of CHF that may profit from NP therapy.

Topics: Acute Disease; Chronic Disease; Cyclic GMP; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Prognosis; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

B-type natriuretic peptides are biomarkers of heart failure (HF) that can decrease following treatment. We sought to determine whether B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) concentration changes occurred in parallel to changes in other measures of heart failure following treatment.. We conducted a systematic review of the literature for studies that assessed B-type natriuretic peptide measurements in treatment monitoring of patients with stable chronic heart failure. Selected studies had to include at least three consecutive measurements of BNP or NT-proBNP.. Of 4338 citations screened, only 12 met all of the selection criteria. The selected studies included populations with a wide range of heart failure severity and therapy. BNP and NT-proBNP decreased following treatment in nine studies and was associated with improvement in clinical measures of HF.. There was limited data to support using BNP or NT-proBNP to monitor therapy in patients with HF.

Topics: Chronic Disease; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are widely being used as biomarkers in acute and chronic heart failure. These cardiac neurohormones are mainly being secreted from the left and right ventricles as a response to ventricular volume expansion, pressure overload and resultant increased wall tension.. Current application of natriuretic peptides is manifold. BNP and NT-proBNP are being used as screening parameters, diagnostic markers, and prognostic indicators or to monitor therapy. However, their usage to diagnose heart failure and possibly in future adjust therapy should not be uncritical.. In the interpretation of natriuretic peptides it has to be considered that several factors such as age, sex, constitution and non-cardiac diseases like renal failure influence plasma levels. Natriuretic peptides may support diagnostics of heart failure in patients with unexplained dyspnea. However, biomarkers should not be used to replace conventional clinical evaluation. The use of natriuretic peptides for screening asymptomatic populations is inappropriate. A BNP-guided titration of heart failure medication is not yet warranted. BNP testing may be used only in selected situations for risk stratification since the prognostic value is still limited by a lack of clear usefulness in guiding clinical management.. The measurement of natriuretic peptides is at present largely an addition in the diagnosis of acute heart failure, as long as possible errors in interpretation are taken into account.

Topics: Acute Disease; Biomarkers; Blood Pressure; Chronic Disease; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis

Heart failure is a major problem in the Unites States. Despite the availability of and increasing adherence to evidence-based guidelines, the morbidity and mortality from this disease remain significant. Strides have been made in the last several years to develop objective tools to aid in the diagnosis of heart failure and in the prognosis of the affected patients. Brain natriuretic peptide (BNP) and the N-terminal prohormone of BNP are neurohormones released in response to ventricular wall stress and/or tension. As objective laboratory measures, both peptides have similar utility in the treatment of patients with heart failure. Currently, these laboratory tests are approved only to aid in diagnosis. However, data are beginning to emerge that suggest the utility of serial BNP monitoring for the management of chronic heart failure in patients with left ventricular dysfunction. Preliminary studies have shown that when added to traditional management combined with adherence to evidenced-based national guidelines, serial monitoring of BNP levels with adjustment of therapy based on the results may improve outcomes in patients with chronic heart failure compared with traditional clinical management alone. Factors that may limit the use or confound interpretation of the laboratory test results include the effects of demographics (e.g., sex, age, body mass index), concurrent diseases, and drug therapies. Several large, outcomes-based studies are under way to examine the use of serial BNP monitoring to decrease morbidity, mortality, and overall health care costs in patients with heart failure.

Topics: Age Factors; Body Mass Index; Cardiovascular Agents; Chronic Disease; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sex Factors

Existing literature on two natriuretic peptides--B-type natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP)--is overwhelming. Both peptides are acknowledged markers for cardiac dysfunction. Most of the sources present data on either BNP or NTproBNP making the comparison difficult. This paper focuses on reviewing studies directly comparing two peptides in the setting of chronic and acute heart failure (HF) and coronary artery disease. Many concomitant diseases influence these two peptides to varying extent. These characteristics should be taken into consideration when interpreting results. For most practical purposes, BNP and NTproBNP are interchangeable, and can be used based on local preferences and availability. NTproBNP seems to be more advantageous for diagnosing mild HF or asymptomatic left ventricular dysfunction.

Topics: Acute Disease; Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Ventricular Dysfunction, Left

Heart failure is common, yet it is difficult to treat. It presents in many different guises and circumstances in which therapy needs to be individualized. The Canadian Cardiovascular Society published a comprehensive set of recommendations in January 2006 on the diagnosis and management of heart failure, and the present update builds on those core recommendations. Based on feedback obtained through a national program of heart failure workshops during 2006, several topics were identified as priorities because of the challenges they pose to health care professionals. New evidence-based recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. Specific recommendations and practical tips were written for the prevention of heart failure, the management of heart failure during intercurrent illness, the treatment of acute heart failure, and the current and future roles of biomarkers in heart failure care. Specific clinical questions that are addressed include: which patients should be identified as being at high risk of developing heart failure and which interventions should be used? What complications can occur in heart failure patients during an intercurrent illness, how should these patients be monitored and which medications may require a dose adjustment or discontinuation? What are the best therapeutic, both drug and nondrug, strategies for patients with acute heart failure? How can new biomarkers help in the treatment of heart failure, and when and how should BNP be measured in heart failure patients? The goals of the present update are to translate best evidence into practice, to apply clinical wisdom where evidence for specific strategies is weaker, and to aid physicians and other health care providers to optimally treat heart failure patients to result in a measurable impact on patient health and clinical outcomes in Canada.

Topics: Acute Disease; Biomarkers; Canada; Cardiac Output, Low; Chronic Disease; Comorbidity; Evidence-Based Medicine; Health Priorities; Heart Failure; Humans; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Risk Factors

Pulmonary hypertension (PH) has long been recognized as a complication of chronic respiratory disease. Recent studies have highlighted the adverse impact PH has on the clinical course of these conditions and have cast doubt on the role of hypoxia in their pathogenesis. Clinicians should carefully consider the possibility of PH during the diagnostic evaluation of chronic respiratory disorders. The usefulness of pharmacologic therapy directed toward PH remains to be determined.

Topics: Chronic Disease; Comorbidity; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Pulmonary Wedge Pressure; Respiratory Tract Diseases; Sleep Apnea Syndromes

We used evidence-based laboratory medicine principles to compare the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) assays for the diagnosis of heart failure.. In May 2006, we performed a computerized literature search of the online National Library of Medicine to select studies specifically designed to compare the diagnostic accuracy of BNP and NT-proBNP assays. The comparison took into account the area under the curve and diagnostic odds ratio (DOR) derived from ROC analysis of original studies.. Both BNP and NT-proBNP assays were found to be clinically useful for the diagnosis of heart failure. Metaanalysis of these data was difficult because of the heterogeneity of data regarding patient population, diagnostic criteria, end-points, and immunoassay methods for both BNP and NT-proBNP. Separate metaanalyses were performed for acute and chronic heart failure. In chronic heart failure, the diagnostic DOR for BNP (8.44, 95% CI 4.66-15.30) was not significantly different from that of NT-proBNP (23.36, 95% CI 9.38-58.19). In patients with acute heart failure, the mean DOR for BNP (16.46, 95% CI 10.65-25.43) was not significantly different from that of NT-proBNP (18.61, 95% CI 12.99-26.65).. Our results indicate that both BNP and NT-proBNP assays have a high degree of diagnostic accuracy and clinical relevance for both acute and chronic heart failure.

Topics: Acute Disease; Chronic Disease; Diagnosis, Differential; Evidence-Based Medicine; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; ROC Curve

Topics: Chronic Disease; Disease-Free Survival; Heart Failure; Humans; Medical History Taking; Natriuretic Peptide, Brain; Patient Education as Topic; Physical Examination; Prognosis; Referral and Consultation

In chronic heart failure (CHF), persistent autonomic derangement and neurohumoral activation cause structural end-organ damage, decrease exercise capacity, and reduce quality of life. Beneficial effects of pharmacotherapy and of exercise training in CHF have been documented at various functional and structural levels. However, pharmacologic treatment can not yet reduce autonomic derangement and neurohumoral activation in CHF to a minimum. Various studies suggest that exercise training is effective in this respect.. After reviewing the available evidence we conclude that exercise training increases baroreflex sensitivity and heart rate variability, and reduces sympathetic outflow, plasma levels of catecholamines, angiotensin II, vasopressin, and brain natriuretic peptides at rest.. Exercise training has direct and reflex sympathoinhibitory beneficial effects in CHF. The mechanism by which exercise training normalizes autonomic derangement and neurohumoral activation is to elucidate for further development of CHF-related training programs aimed at maximizing efficacy while minimizing workload.

Topics: Arginine; Autonomic Nervous System Diseases; Baroreflex; Catecholamines; Chronic Disease; Endothelins; Exercise Therapy; Heart Failure; Heart Rate; Humans; Natriuretic Peptide, Brain; Neurotransmitter Agents; Renin-Angiotensin System; Treatment Outcome; Vasopressins

Topics: Acute Disease; Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Severity of Illness Index

Topics: Adrenergic beta-Antagonists; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Propanolamines; Randomized Controlled Trials as Topic; Stroke Volume; Time Factors

Chronic heart failure (CHF) is a major public health problem causing considerable morbidity and mortality. Recently, plasma homocysteine (HCY) has been suggested to be significantly increased in CHF patients. This article reviews the relation between hyperhomocysteinemia (HHCY) and CHF. Clinical data indicate that HHCY is associated with an increased incidence, as well as severity, of CHF. In addition, HCY correlates with brain natriuretic peptide (BNP), a modern biochemical marker of CHF, which is used for diagnosis, treatment guidance and risk assessment. Animal studies showed that experimental HHCY induces systolic and diastolic dysfunction, as well as an increased BNP expression. Moreover, hyperhomocysteinemic animals exhibit an adverse cardiac remodeling characterized by accumulation of interstitial and perivascular collagen. In vitro superfusion experiments with increasing concentrations of HCY in the superfusion medium stimulated myocardial BNP release independent from myocardial wall stress. Thus, clinical and experimental data underline a correlation between HHCY and BNP supporting the role of HHCY as a causal factor for CHF. The mechanisms leading from an elevated HCY level to reduced pump function and adverse cardiac remodeling are a matter of speculation. Existing data indicate that direct effects of HCY on the myocardium, as well as nitric oxide independent vascular effects, are involved. Preliminary data from small intervention trials have initiated the speculation that HCY lowering therapy by micronutrients may improve clinical as well as laboratory markers of CHF. In conclusion, HHCY might be a potential etiological factor in CHF. Future studies need to explore the pathomechanisms of HHCY in CHF. Moreover, larger intervention trials are needed to clarify whether modification of plasma HCY by B-vitamin supplementation improves the clinical outcome in CHF patients.

Topics: Animals; Chronic Disease; Heart Failure; Homocysteine; Humans; Natriuretic Peptide, Brain

Hypoxia and endothelial dysfunction play a central role in the development of pulmonary hypertension. Cor pulmonale is a maladaptive response to pulmonary hypertension. The presence of peripheral edema in cor pulmonale is almost invariably associated with hypercapnia. Correction of abnormalities of gas exchange and ventilation can ameliorate pulmonary hypertension and improve survival. This review focuses on new information about the pathogenesis and treatment of pulmonary hypertension in COPD including information derived from lung volume reduction surgery, the role of brain natriuretic peptide, exhaled nitric oxide for diagnosis, and the treatment of cor pulmonale with recently available specific pulmonary vasodilators.

Topics: Chronic Disease; Comorbidity; Humans; Hypertension, Pulmonary; Natriuretic Agents; Natriuretic Peptide, Brain; Nitric Oxide; Phlebotomy; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease

Brain natriuretic peptide (BNP) is a counter-regulatory hormone produced mainly by ventricular myocardium. Early research studies were performed to ascertain its value in the diagnosis of congestive heart failure in acute care settings. Subsequent studies have explored its utility in screening for asymptomatic left ventricular dysfunction in the community, determining prognosis in coronary artery disease, appropriate timing of surgery in valve disorders, and in evaluating many other cardiac diseases. This review summarizes the current status of medical literature, introduces a new test to the insurance industry.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Humans; Insurance, Life; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Adjustment; United States

Topics: Biomarkers; Chronic Disease; Diagnostic Imaging; Edema; Heart Failure; Humans; Natriuretic Peptide, Brain; Norepinephrine; Pleural Effusion; Renin-Angiotensin System; Respiration Disorders; Stroke Volume; Ventricular Remodeling

Biomarkers are substances that reflect the presence of a given disease, its pathophysiology or organ damage. These indicators are increasingly proposed to assess prognosis or the response to treatment. This review examines the value of a series of biomarkers which have been recently tested in prospective studies in chronic kidney disease and end-stage renal disease patients.. C reactive protein has coherently emerged as an early marker of renal dysfunction. The usefulness of this measurement for predicting the evolution of chronic kidney disease or for monitoring the response to renoprotective treatment, however, still remains unproven. On the other hand the measurement of C reactive protein can be recommended for monitoring the risk of atherosclerotic complications in patients with chronic kidney disease and end-stage renal disease, particularly in those with evidence of coronary heart disease or other cardiovascular complications (i.e. in the vast majority of patients followed up in nephrology clinics). There is growing interest in homocysteine and asymmetric dimethyl arginine as biomarkers of cardiovascular and renal risk but the usefulness of these biomarkers in clinical practice remains to be proven. Brain natriuretic peptide and troponin T are strongly related to cardiovascular outcomes in end-stage renal disease patients but their value in this population still requires to be proper tested in specifically designed intervention studies.. Among emerging biomarkers C reactive protein is the only one which is very near to fulfilling the methodological requirements for being recommended in clinical practice.

Topics: Animals; Arginine; Biomarkers; C-Reactive Protein; Chronic Disease; Disease Progression; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Troponin T

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Pacing, Artificial; Cardiography, Impedance; Cardiomyopathy, Dilated; Chronic Disease; Clinical Trials as Topic; Comorbidity; Disease Management; Enoximone; Heart Failure; Hemodynamics; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Natriuretic Peptides; Nitric Oxide; Nitric Oxide Synthase; Pacemaker, Artificial; Phosphodiesterase Inhibitors; Practice Guidelines as Topic; Xanthine Oxidase

Recent findings on the relationship between congestive heart failure and renal failure are summarized in this review.. Congestive heart failure is found in about one-quarter of cases of chronic kidney disease. The most common cause of congestive heart failure is ischemic heart disease. The prevalence of congestive heart failure increases greatly as the patient's renal function deteriorates, and, at end-stage renal disease, can reach 65-70%. There is mounting evidence that chronic kidney disease itself is a major contributor to severe cardiac damage and, conversely, that congestive heart failure is a major cause of progressive chronic kidney disease. Uncontrolled congestive heart failure is often associated with a rapid fall in renal function and adequate control of congestive heart failure can prevent this. The opposite is also true: treatment of chronic kidney disease can prevent congestive heart failure. There is new evidence showing the cardioprotective effect of carvedilol in patients on dialysis, and of simvastatin and eplerenone in patients with congestive heart failure. Use of non-steroidal anti-inflammatory drugs doubles the rate of hospitalization in patients with congestive heart failure. Anemia has been found in one-third to half the cases of congestive heart failure, and may be caused not only by chronic kidney disease but by the congestive heart failure itself. The anemia is associated with worsening cardiac and renal status and often with signs of malnutrition. Control of the anemia and aggressive use of the recommended medication for congestive heart failure may improve the cardiac function, patient function and exercise capacity, stabilize the renal function, reduce hospitalization and improve quality of life. Congestive heart failure, chronic kidney disease and anemia therefore appear to act together in a vicious circle in which each condition causes or exacerbates the other. Both congestive heart failure and anemia are often undertreated. Cooperation between nephrologists and other physicians in the treatment of patients with anemic congestive heart failure may improve the quality of care and the subsequent prognosis for both congestive heart failure and chronic kidney disease.. Adequate and early detection and aggressive treatment of congestive heart failure and chronic kidney disease and the associated anemia may markedly slow the progression of both diseases.

Topics: Anemia; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Heart Failure; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Uremia

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Renin-Angiotensin System

Topics: Acute Disease; Age Factors; Aged; Chronic Disease; Dyspnea; Geriatric Assessment; Heart Failure; Humans; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Patient Selection; Prognosis; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index

A HORMONE REVEALING VENTRICULAR DYSFUNCTION: B-type natriuretic peptide or Brain natriuretic peptide (BNP) is a neurohormone secreted by the ventricular myocytes in response to volume expansion and pressure overload. It is a sensitive marker of ventricular dysfunction in symptomatic and asymptomatic patients, and its dosage is correlated with the severity of the dysfunction. INDICATION FOR ITS DOSAGE IN HEART FAILURE: Since the results of recent studies, many authors recommend its routine use in heart failure, in order to confirm the diagnosis in difficult cases, assess severity, prognosis and the efficacy of treatment. Such use requires that the results of these studies be known and that the threshold value be adapted according to the age, concomitant diseases and indication of the dosage. OTHER AFFECTIONS: Its diagnostic and prognostic interest in acute coronary syndromes and hypertension is presently being studied.

Topics: Acute Disease; Angina, Unstable; Chronic Disease; Clinical Trials as Topic; Diagnosis, Differential; Dyspnea; Emergencies; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Risk Factors; ROC Curve; Sensitivity and Specificity; Troponin; Ventricular Dysfunction; Ventricular Remodeling

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles, which is released as N-terminal pro-brain natriuretic peptide (NT-proBNP) and then enzymatically cleaved in to the NT fragment and the immunoreactive BNP. Both tests have been used to identify patients with congestive heart failure (CHF). Important considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, and the interpretation of their units of measure. In general, a BNP level below 100 pg/mL has strong negative predictive value in the assessment of patients with dyspnea caused by a disorder other than CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated heart failure, and the peptide has been shown to be a reliable independent predictor of sudden cardiac death. In the absence of renal dysfunction NT-proBNP has also been shown to be an independent predictor of sudden death in CHF patients. Because both a large area of myonecrosis or concomitant left ventricular failure are related to prognosis in acute coronary syndromes, B-type natriuretic peptides have also been linked to outcomes in this condition. This article describes the physiology and timing of release of B-type natriuretic peptides and the rationale for their use in the following settings: 1) evaluation of decompensated CHF, 2) screening for chronic CHF, 3) prognosis of CHF and sudden death, and 4) prognosis in acute coronary syndromes with inferred left ventricular dysfunction.

Topics: Atrial Natriuretic Factor; Brain; Chronic Disease; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity

Brain natriuretic peptide (BNP) has been established as a new and reliable laboratory marker for chronic heart failure (CHF). BNP is a neurohormone secreted by the cardiac ventricles in response to volume expansion and pressure overload. It is released as N-terminal pro-brain natriuretic peptide and then Korrelaenzymatically cleaved into the NT fragment and the immunoreactive BNP. BNP promotes vasodilatation, natriuresis, diuresis, and inhibits the renin-angiotensin- aldosterone system. BNP values depend on sex, age, renal function, and the assay used. BNP exhibits a high sensitivity and specificity for the diagnosis of CHF. BNP determination improves the differential diagnosis of acute dyspnea. Normal BNP levels are found, if dyspnea is caused by pulmonary disease, pathologic BNP values are typical of a cardiac disorder. In CHF, BNP levels can be used as a reliable independent predictor of cardiac death or deterioration of cardiac functional status at follow-up. As a general screening test for CHF, BNP is of limited value due to a substantial number of false positive test results, which lead to further cardiac diagnostic testing. BNP is helpful for the assessment of the success of CHF therapy in acute cardiac decompensation and outpatients. An individually tailored CHF therapy with serial determination of BNP opens up new perspectives for a more objective and effective treatment of CHF patients.

Topics: Biomarkers; Chronic Disease; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Reference Values; Ventricular Dysfunction, Left

The aim of our observational study was to derive a small set out of 92 repeatedly measured biomarkers with optimal predictive capacity for adverse clinical events in heart failure, which could be used for dynamic, individual risk assessment in clinical practice. In 250 chronic HFrEF (CHF) patients, we collected trimonthly blood samples during a median of 2.2 years. We selected 537 samples for repeated measurement of 92 biomarkers with the Cardiovascular Panel III (Olink Proteomics AB). We applied Least Absolute Shrinkage and Selection Operator (LASSO) penalization to select the optimal set of predictors of the primary endpoint (PE). The association between repeatedly measured levels of selected biomarkers and the PE was evaluated by multivariable joint models (mvJM) with stratified fivefold cross validation of the area under the curve (cvAUC). The PE occurred in 66(27%) patients. The optimal set of biomarkers selected by LASSO included 9 proteins: NT-proBNP, ST2, vWF, FABP4, IGFBP-1, PAI-1, PON-3, transferrin receptor protein-1, and chitotriosidase-1, that yielded a cvAUC of 0.88, outperforming the discriminative ability of models consisting of standard biomarkers (NT-proBNP, hs-TnT, eGFR clinically adjusted) - 0.82 and performing equally well as an extended literature-based set of acknowledged biomarkers (NT-proBNP, hs-TnT, hs-CRP, GDF-15, ST2, PAI-1, Galectin 3) - 0.88. Nine out of 92 serially measured circulating proteins provided a multivariable model for adverse clinical events in CHF patients with high discriminative ability. These proteins reflect wall stress, remodelling, endothelial dysfunction, iron deficiency, haemostasis/fibrinolysis and innate immunity activation. A panel containing these proteins could contribute to dynamic, personalized risk assessment.Clinical Trial Registration: 10/05/2013 https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 .

Topics: Aged; Antigens, CD; Aryldialkylphosphatase; Biomarkers; Chronic Disease; Fatty Acid-Binding Proteins; Female; Galectin 3; Growth Differentiation Factor 15; Heart Failure; Hexosaminidases; Humans; Immunity, Innate; Insulin-Like Growth Factor Binding Protein 1; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Plasminogen Activator Inhibitor 1; Precision Medicine; Receptors, Transferrin; Risk Assessment; Risk Factors

Heart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers.. Sixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups.. There was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002).. Ivabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF. Trial registration Date: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure-Full Text View-ClinicalTrials.gov.

Topics: Anti-Arrhythmia Agents; Biomarkers; Chronic Disease; Diuretics; Heart Failure; Humans; Ivabradine; Natriuretic Peptide, Brain; Neopterin; Stroke Volume

To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG).. This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial.. At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group.. In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Double-Blind Method; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Quality of Life; Stroke Volume; Ventricular Function, Left

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents.. This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents.. Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup.. The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015.

Topics: Aged; Biomarkers; Blood Glucose; Canagliflozin; Chronic Disease; Diabetes Mellitus, Type 2; Female; Glycemic Control; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prognostic value versus a marker of higher risk chronic HF patients is unclear.. After excluding patients with new-onset HF, the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) included 4205 patients hospitalized for worsening chronic HF with reduced or preserved ejection fraction. The present analysis compared patients by presence or absence of prior HF hospitalization within 12 months and by timing of prior HF hospitalization relative to index hospitalization. Associations with 180-day all-cause mortality were assessed, including adjustment for 27 prespecified clinical factors.. In this cohort of patients hospitalized for worsening HF, prior HF hospitalization was not associated with 180-day mortality after comprehensively accounting for patient characteristics measured during the index patient visit. Clinical confounders measured at the point-of-care may explain previously observed associations between prior HF hospitalization and mortality, and these clinical factors may be a more direct means of predicting patient survival. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00475852.

Topics: Aged; Chronic Disease; Disease Progression; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Factors; Stroke Volume; Survival Rate

Chronic heart failure (CHF) seriously affects the quality of patients' lives. Sacrubitril/valsartan is a combination angiotensin receptor-neprilysin inhibitor, a new therapeutic drugs to treat CHF.This study aims to observe the impact of sacrubitril/valsartan on clinical treatment and high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-ProBNP) serum levels, the improvement of the left atrial diameter (LAD) and left ventricular end diastolic dimension (LVEDD), and the left ventricular ejection fraction (LVEF) in patients with CHF.120 patients were randomly divided into a sacrubitil/valsartan group and a valsantan group, with 60 cases in each. Patients in the sacrubitil/valsartan group were administered sacrubitril/valsartan; while in the valsantan group, they were administered valsartan. The clinical effects, adverse reactions, and rehospitalization were observed eight weeks later, and hs-cTnT and NT-ProBNP serum levels and LAD, LVEDD, and LVEF were assayed.There were 53 cases of positive effect in the sacrubitil/valsartan group and 42 in the valsartan group (P < 0.05). Eight participants demonstrated adverse reactions in the sacrubitil/valsartan group, while 17 in the control group (P < 0.05). Hs-cTnT and NT-ProBNP serum levels, the measurements of LAD, LVEDD, and LVEF in the sacrubitil/valsartan group before the treatments were (24.47 ± 7.54) pg/mL, (10,356.94 ± 5,447.68) pg/mL, (49.41 ± 5.22) mm, (68.06 ± 6.20) mm and (31.12 ±6.65) %; in the valsartan group were (29.752 ± 10.03) pg/mL, (9,518.17 ± 5,905.17) pg/mL, (49.65 ± 4.91) mm, (67.06 ± 3.97) mm, and (30.41 ± 6.11) % (P > 0.05), while in the sacrubitil/valsartan group, the values decreased after the treatments to (17.92 ± 4.74) pg/mL, (3,881.59 ± 2,087.79) pg/mL, (42.18 ± 4.87) mm, (60.35 ± 7.12) mm and (45.35 ± 4.49) %; in the valsartan group to (25.81 ± 7.36) pg/mL, (6,278.35 ± 2,643.11) pg/mL, (46.53 ± 4.80) mm, (64.51 ± 4.34) mm, and (36.47 ± 5.21) % (P < 0.05). There were significant differences within the same group, before and after treatments (P < 0.05).Sacrubitril/valsartan treatment of patients with CHF improves their symptoms and is deserving of clinical application. This is also evident from significantly improved levels of serum hs-cTnT and NT-ProBNP and the left ventricular function.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Biomarkers; Chronic Disease; Drug Combinations; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Treatment Outcome; Troponin T; Valsartan; Ventricular Function, Left

Heart failure (HF) is the final stage of various cardiac diseases with poor prognosis. The integrated traditional Chinese medicine (TCM) and western medicine therapy has been considered as a prospective therapeutic strategy for chronic heart failure (CHF). There have been small clinical trials and experimental studies to demonstrate the efficacy of Shenfu Qiangxin Pills (SFQX) for treating CHF, however, there is still a lack of further high-quality trial. This paper describes the protocol for the clinical assessment of SFQX in CHF (heart-kidney Yang deficiency syndrome) patients.. A randomized, double-blind, parallel-group, placebo-controlled, multi-center trial will assess the efficacy and safety of SFQX in the treatment of CHF. 352 patients with CHF (heart-kidney Yang deficiency syndrome) from 22 hospitals in China will be enrolled. Besides their standardized western medicine, patients will be randomized to receive treatment of either SFQX or placebo for 12 weeks. The primary outcome is the plasma N-terminal pro-B-type natriuretic peptide levels, which will be measured uniformly by the central laboratory. The secondary outcomes include composite endpoint events (hospitalization due to worsening HF, all-cause mortality, other serious cardiovascular events), echocardiography indicators, grades of the New York Heart Association (NYHA) functional classification, the 6-minute walk test (6MWT) results, Minnesota Living With Heart Failure Questionnaire and TCM syndrome scores.. The integrated TCM and western medicine therapy has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of SFQX in the treatment of CHF.. Chinese Clinical Trial Registry: ChiCTR2000028777 (registered on January 3, 2020).

Topics: Case-Control Studies; China; Chronic Disease; Double-Blind Method; Drugs, Chinese Herbal; Echocardiography; Heart; Heart Failure; Hospitalization; Humans; Medicine, Chinese Traditional; Natriuretic Peptide, Brain; Peptide Fragments; Placebos; Safety; Treatment Outcome; Walk Test; Yang Deficiency

Nowadays, the potential beneficial effects of probiotic yogurt as a functional food has raised much interest. Thus, the aim of this study was to compare the probiotic yogurt and ordinary yogurt consumption on some indices in patients with chronic heart failure (CHF).. In this randomized, triple-blind clinical trial, 90 patients with CHF were randomly allocated into two groups to take either probiotic yogurt or ordinary yogurt for 10 weeks. The serum levels of pentraxin3 (PTX3), N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low density lipoprotein (oxLDL), and apolipoprotein B100 (ApoB100) were measured at the baseline and at the end of week 10. P-Value <0.05 was defined as statistically significant. Final analyses were performed on 78 patients. The levels of PTX3 and oxLDL in both the groups decreased significantly after 10 weeks, and these reductions were greater in the probiotic group, where the difference between the groups was statistically significant for oxLDL (P-value: 0.051, adjusted P-value: 0.010) but not significant for PTX3 (P-value: 0.956, adjusted P-value: 0.236). The changes in the serum NT-proBNP levels were not statistically significant between the groups (P-value: 0.948, adjusted P-value: 0.306). ApoB100 significantly decreased in the control group compared to the probiotic group and the difference between the groups was significant at first but was not significant after adjusting for the confounders (P-value: 0.004, adjusted P-value: 0.280).. The serum oxLDL significantly reduced due to probiotic yogurt consumption after 10 weeks compared to ordinary yogurt; thus, it may be useful for improving the oxidative status of CHF patients. The clinical trial registry number is IRCT20091114002709N48 (https://www.irct.ir/IRCT20091114002709N48, registered 12 March 2018).

Topics: Adult; Aged; Aged, 80 and over; Apolipoprotein B-100; C-Reactive Protein; Chronic Disease; Female; Heart Failure; Humans; Lipoproteins, LDL; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Probiotics; Serum Amyloid P-Component; Yogurt

The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial demonstrated that a strategy to "guide" application of guideline-directed medical therapy (GDMT) by reducing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) was not superior to GDMT alone.. The purpose of this study was to examine the prognostic meaning of NT-proBNP changes following heart failure (HF) therapy intensification relative to the goal NT-proBNP value of 1,000 pg/ml explored in the GUIDE-IT trial.. A total of 638 study participants were included who were alive and had available NT-proBNP results 90 days after randomization. Rates of subsequent cardiovascular (CV) death/HF hospitalization or all-cause mortality during follow-up and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were analyzed.. A total of 198 (31.0%) subjects had an NT-proBNP ≤1,000 pg/ml at 90 days with no difference in achievement of NT-proBNP goal between the biomarker-guided and usual care arms. NT-proBNP ≤1,000 pg/ml by 90 days was associated with longer freedom from CV/HF hospitalization or all-cause mortality (p < 0.001 for both) and lower adjusted hazard of subsequent HF hospitalization/CV death (hazard ratio: 0.26; 95% confidence interval: 0.15 to 0.46; p < 0.001) and all-cause mortality (hazard ratio: 0.34; 95% confidence interval: 0.15 to 0.77; p = 0.009). Regardless of elevated baseline concentration, an NT-proBNP ≤1,000 pg/ml at 90 days was associated with better outcomes and significantly better KCCQ overall scores (p = 0.02).. Patients with heart failure with reduced ejection fraction whose NT-proBNP levels decreased to ≤1,000 pg/ml during GDMT had better outcomes. These findings may help to understand the results of the GUIDE-IT trial. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Prognosis; Stroke Volume; Treatment Outcome

Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF).. PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate.. In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function.. ClinicalTrials.gov Identifier NCT02992288.

Topics: Adenosine A1 Receptor Agonists; Aged; Chronic Disease; Dipeptides; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pyridines; Stroke Volume; Survival Rate; Treatment Outcome

To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-al- pha (TNF-α) and nuclear factor-kappa B (NF-κB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.. A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure) were enrolled. Patients were randomly divided into the control group and Jiawei Shenfu group. All patients received standard medications for treatment of chronic heart failure. Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily. Treatments continued for 4 consecutive weeks. The primary endpoint was the change in plasma B-type natriuretic peptide (BNP), NF-κB, and TNF-α levels during 4 weeks of treatment.. At the 4-week follow-up, a significant reduction in BNP levels compared with baseline was observed in both groups, but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group. The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score, the Chinese medicine syndrome score, heart rate, left ventricular ejection fraction, and 6-min walking distance compared with the control group. The degree of changes in NF-κB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.. Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function, and reduce BNP levels. The mechanism may be related to inhibition of pro-inflamma- tory cytokines and the NF-κB-induced kinase pathway, leading to amelioration of the inflammatory response.

Topics: Adult; Aged; Chronic Disease; Double-Blind Method; Drugs, Chinese Herbal; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; NF-kappa B; Tumor Necrosis Factor-alpha

Renal denervation (RDN) is as an effective treatment for heart failure (HF), but its effects on cardiac function of patients with HF are not well documented. Here, the aim was to investigate RDN's effect on patients with chronic systolic HF, by conducting a single-center, prospective, randomized, and controlled study.. Sixty patients with chronic systolic HF were randomly assigned to the RDN or control groups, receiving percutaneous catheter-based RDN with radiofrequency ablation and drug treatment, respectively. All patients performed a 6-minute walk test, echocardiography, blood pressure measurement, and biochemical test, at both baseline and in a 6-month follow up.. Over 6-month follow up, patients in RDN group showed a decrease in N-terminal pro-B-type natriuretic peptide (440.1 ± 226.5 pg/mL vs. 790.8 ± 287.0 pg/mL, p < 0.001, Cohen's d = 1.14), an increase in left ventricular ejection fraction (39.1 ± 7.3% vs. 35.6 ± 3.3%, p = 0.017, Cohen's d = 0.61), improved New York Heart Association class assessment (p = 0.01, Cohen's d = 0.66), and decreased blood pressures (p < 0.001, Cohen's d = 0.91), without reporting hypotension and syncope amaurosis. No significant between-group difference was observed for glomerular filtration rate and heart rate.. Renal denervation which effectively and safely improves patient's cardiac function as well as exercise tolerance, could be considered as an effective treatment for chronic systolic HF.

Topics: Biomarkers; Catheter Ablation; China; Chronic Disease; Exercise Tolerance; Heart Failure, Systolic; Humans; Kidney; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Recovery of Function; Renal Artery; Stroke Volume; Sympathectomy; Time Factors; Treatment Outcome; Ventricular Function, Left

Our aim was to explore potential use of temporal profiles of seven emerging cardio-renal and two pulmonary candidate biomarkers for predicting future adverse clinical outcome in stable patients with chronic heart failure (CHF).. In 263 CHF patients, we determined the risk of a composite endpoint of HF-hospitalization, cardiac death, LVAD-placement and heart transplantation in relation to repeatedly assessed (567 samples in total) blood biomarker levels, and slopes of their temporal trajectories (i.e., rate of biomarker change per year). In each patient, we estimated biomarker trajectories using repeatedly measured osteopontin (OPN), osteoprotegerin (OPG), epidermal growth factor receptor (EGFR), heparin-binding protein (HBP), trefoil factor-3 (TFF3), kallikrein-6 (KLK-6), matrix extracellular phosphoglycoprotein (MEPE), pulmonary surfactant-associated protein-D (PSP-D), and secretoglobulin family 3A-member-2 (SCGB3A2).. During 2.2 years of follow-up, OPN, OPG, and HBP levels predicted the composite endpoint (univariable hazard ratio [95% confidence interval] per 1SD increase: 2.31 [1.76-3.15], 2.23 [1.69-3.00], and 1.36[1.09-1.70]). Independently of the biomarkers' levels, the slopes of OPG, TFF-3, PSP-D trajectories were also strong clinical predictors (per 0.1SD increase: 1.24 [1.14-1.38], 1.31 [1.17-1.49], and 1.32 [1.21-1.47]). All associations persisted after multivariable adjustment for baseline characteristics, and repeatedly assessed CHF pharmacological treatment and cardiac biomarkers NT-proBNP and troponin T.. Repeatedly-measured levels of OPN, OPG, and HBP, and slopes of OPG, TFF-3, and PSP-D strongly predict clinical outcome. These candidate biomarkers may be clinically relevant as they could further define a patient's risk and provide additional pathophysiological insights into CHF.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cohort Studies; ErbB Receptors; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Kidney; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Osteoprotegerin; Peptide Fragments; Prospective Studies; Time Factors

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) is an international, multicentre, parallel group, randomized, double-blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N-terminal pro B-type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m. DAPA-HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.

Topics: Benzhydryl Compounds; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Glucosides; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Patient Reported Outcome Measures; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Reports that sodium glucose cotransporter 2 inhibitors decrease cardiovascular death and events in patients with diabetes have attracted attention in the cardiology field. We conducted a study of canagliflozin in patients with chronic heart failure and type II diabetes.. Thirty-five Japanese patients with chronic heart failure and type II diabetes were treated with canagliflozin for 12 months. The primary endpoints were the changes of subcutaneous, visceral, and total fat areas at 12 months determined by computed tomography. Secondary endpoints included markers of glycemic control, renal function, and oxidative stress, as well as lipid parameters, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), flow-mediated dilation (FMD), and echocardiographic left ventricular function.. All fat areas (subcutaneous, visceral, and total) showed a significant decrease at 12 months. ANP and BNP also decreased significantly, along with improvement of renal function, oxidized LDL, and E/e', FMD increased significantly after canagliflozin treatment.. Canagliflozin demonstrated cardiac and renal protective effects as well as improving oxidative stress, diastolic function, and endothelial function. This drug was effective in patients who had heart failure with preserved ejection fraction and could become first-line therapy for such patients with diabetes. Trial registration UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000021239.

Topics: Adiposity; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Canagliflozin; Chronic Disease; Diabetes Mellitus, Type 2; Female; Heart; Heart Failure; Humans; Japan; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Weight Loss

Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb) <13 g/dL (male) or <12 g/dL (female) and the remaining 290 did not ([N]). Allocated and achieved doses of carvedilol were similar. Left ventricular ejection fraction (LVEF) and plasma B-type natriuretic peptide (BNP) level significantly improved in both groups over 56 weeks, but they were smaller in [A] than in [N] (LVEF, P=0.046; BNP, P<0.0001 by ANOVA). Baseline Hb was an independent predictor of absolute change in LVEF (β=0.13, P=0.047) and BNP (β=-0.10, P=0.01). Presence of chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m. Our data suggested that anemia was associated with a blunted response to carvedilol in HFrEF patients.

Topics: Adrenergic beta-Antagonists; Aged; Anemia; Carvedilol; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke Volume

The correlation between serum adiponectin concentration and hemodynamics or certain metabolic markers in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is unknown.Methods and Results:We enrolled 30 CTEPH patients who underwent interventional therapy of balloon pulmonary angioplasty or pulmonary endarterectomy. Serum adiponectin concentrations positively correlated with B-type natriuretic peptide (BNP) concentrations, pulmonary vascular resistance, and mean pulmonary arterial pressure. After the therapeutic interventions, serum adiponectin concentrations improved and changes in serum adiponectin concentrations significantly correlated with changes in BNP concentrations.. Adiponectin can be a useful marker for the severity of CTEPH.

Topics: Adiponectin; Aged; Angioplasty, Balloon; Biomarkers; Chronic Disease; Endarterectomy; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index

Chronic heart failure (CHF), a clinical syndrome resulting from the consequences of various cardiovascular diseases (CVDs), is increasingly becoming a global cause of morbidity and mortality. We had earlier demonstrated that a 4-day forest bathing trip can provide an adjunctive therapeutic influence on patients with CHF. To further investigate the duration of the impact and the optimal frequency of forest bathing trips in patients with CHF, we recruited those subjects who had experienced the first forest bathing trip again after 4 weeks and randomly categorized them into two groups, namely, the urban control group (city) and the forest bathing group (forest). After a second 4-day forest bathing trip, we observed a steady decline in the brain natriuretic peptide levels, a biomarker of heart failure, and an attenuated inflammatory response as well as oxidative stress. Thus, this exploratory study demonstrated the additive benefits of twice forest bathing trips in elderly patients with CHF, which could further pave the way for analyzing the effects of such interventions in CVDs.

Topics: Aged; Chronic Disease; Complementary Therapies; Forests; Heart Failure; Heart Function Tests; Humans; Interleukin-6; Natriuretic Peptide, Brain; Oxidative Stress; Recreation; Treatment Outcome; Tumor Necrosis Factor-alpha

Hyperuricemia has a close relationship with cardiovascular diseases including heart failure. However, it is controversial whether xanthine oxidase inhibition has benefits for patients with chronic heart failure. We designed the Effect of Xanthine Oxidase Inhibitor in Chronic Heart Failure Patients Complicated with Hyperuricemia study (Excited-UA study) to compare the beneficial effects between a novel xanthine oxidoreductase inhibitor, topiroxostat, and a conventional agent, allopurinol, in patients with chronic heart failure and hyperuricemia. We focus on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiography-based cardiac function, vascular endothelial function, renal function, inflammation, and oxidative stress.. The excited-UA is a prospective, randomized, open-label, blinded-endpoint clinical trial designed to prove our hypothesis that topiroxostat is more effective than allopurinol in patients with chronic heart failure and hyperuricemia. A total of 140 patients with chronic heart failure and hyperuricemia (plasma brain natriuretic peptide level ≥ 40 pg/mL and serum uric acid level ≥ 7.0 mg/dL) are randomly assigned (ratio 1:1) into either the topiroxostat group (40-160 mg/day) or allopurinol group (100-300 mg/day), to achieve the target uric acid level of 6.0 mg/dL. According to the protocol, all patients are followed up annually for 24 weeks. The primary endpoint is percent change in serum NT-proBNP level at 24 weeks from baseline.. The Excited-UA study would provide novel evidence for the clinical relevancy of xanthine oxidoreductase inhibitor treatment in patients with chronic heart failure and hyperuricemia.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Chronic Disease; Echocardiography; Enzyme Inhibitors; Heart Failure; Humans; Hyperuricemia; Middle Aged; Natriuretic Peptide, Brain; Nitriles; Peptide Fragments; Pyridines; Randomized Controlled Trials as Topic; Research Design; Xanthine Oxidase; Young Adult

Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines (IL-6, IL-1β, IL-8, TNF-α and IL-4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices.. We enrolled 32 subjects (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically.. All investigated biomarkers were significantly higher in CHF patients than in non-CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1β levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT-proBNP, CS IL-6 and CS IL-1β serum concentrations were inversely related to the echocardiographically determined left ventricular ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = -0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL-1β (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r = 0.43, P = 0.015), TNF-α (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002).. CS sampling of NT-proBNP, CA 125 and pro-anti-inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation.

Topics: Aged; CA-125 Antigen; Chronic Disease; Coronary Sinus; Female; Heart Failure; Humans; Interleukin-1beta; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure. The aim of the study is to determine whether a urate-lowering agent febuxostat, an inhibitor of xanthine oxidase, may improve the clinical outcomes in chronic heart failure patients with hyperuricemia when compared to conventional treatment. This multicenter, prospective, randomized, open-label, blinded endpoint study with a follow-up period of 24 weeks will enroll 200 Japanese chronic heart failure patients with hyperuricemia. The eligibility criteria include a diagnosis of chronic heart failure (New York Heart Association functional class II-III with a history of hospitalization due to worsening of heart failure within the last 2 years), reduced left ventricular systolic function (left ventricular ejection fraction < 40%) and increased plasma natriuretic peptide [plasma B-type natriuretic peptide (BNP) ≥ 100 pg/mL or N-terminal pro BNP (NT-proBNP) ≥ 400 pg/mL], and hyperuricemia (serum uric acid >7.0 mg/dL and ≤ 10 mg/dL) at the screening visit. The primary outcome is the difference in the plasma BNP levels between the baseline and 24 weeks of treatment. The plasma BNP levels are measured in the central laboratory in a blinded manner. This study investigates the efficacy and safety of febuxostat in chronic heart failure patients with hyperuricemia.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Febuxostat; Female; Gout Suppressants; Heart Failure; Hospitalization; Humans; Hyperuricemia; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Function, Left

To determine tolerability and the optimal dose regimen of the soluble guanylate cyclase stimulator vericiguat in patients with chronic heart failure and preserved ejection fraction (HFpEF).. SOCRATES-PRESERVED was a prospective, randomized, placebo-controlled double-blind, Phase 2b dose-finding study in patients with HFpEF (ejection fraction ≥ 45%). Patients received vericiguat once daily at 1.25 or 2.5 mg fixed doses, or 5 or 10 mg titrated from a 2.5 mg starting dose, or placebo for 12 weeks. The two primary endpoints were change from baseline in log-transformed N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and left atrial volume (LAV) at 12 weeks. Patients (N = 477; 48% women; mean age 73 ± 10 years; baseline atrial fibrillation 40%) were randomized within 4 weeks of HF hospitalization (75%) or outpatient treatment with intravenous diuretics for HF (25%) to vericiguat (n = 384) or placebo (n = 93). In the pooled three highest dose arms change in logNT-proBNP (vericiguat: +0.038 ± 0.782 log(pg/mL), n = 195; placebo: -0.098 ± 0.778 log(pg/mL), n = 73; one-sided P = 0.8991, two-sided P = 0.2017), and change in LAV [vericiguat: -1.7 ± 12.8 mL (n = 194); placebo:  -3.4 ± 12.7 mL (n = 67), one-sided P = 0.8156, two-sided P = 0.3688] were not different from placebo. Vericiguat was well tolerated (adverse events: vericiguat 10 mg arm, 69.8%; placebo, 73.1%), with low discontinuation rates in all groups, and no changes in blood pressure at 10 mg compared with placebo. The pre-specified exploratory endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score improved in the vericiguat 10 mg arm by mean 19.3 ± 16.3 points [median 19.8 (interquartile range 10.4-30.7)] from baseline (mean difference from placebo 9.2 points).. Vericiguat was well tolerated, did not change NT-proBNP and LAV at 12 weeks compared with placebo but was associated with improvements in quality of life in patients with HFpEF. Given the encouraging results on quality of life, the effects of vericiguat in patients with HFpEF warrant further study, possibly with higher doses, longer follow-up and additional endpoints.

Topics: Aged; Atrial Function, Left; Cardiotonic Agents; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pyrimidines; Soluble Guanylyl Cyclase; Stroke Volume; Treatment Outcome

To define the role of single or serial measurement of endothelin 1 (ET-1) for prognostication beyond traditional and modern markers of risk in heart failure (HF).. In total, 115 patients with chronic systolic HF were followed for 10 months. Clinical assessment and ET-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP), highly sensitive troponin I (hsTnI), soluble ST2 (sST2), and galectin 3 were measured at each visit.. Elevated ET-1 was associated with worse HF, lower right ventricular function, higher pulmonary pressure, and higher left atrial volume index despite similar left ventricular function. ET-1 correlated with angiotensin-converting enzyme inhibitor use. A model containing traditional risk factors, ET-1, NT-proBNP, hsTnI, and sST2 best predicted cardiovascular events, and ET-1 improved reclassification. In an adjusted time-integrated model, percent time spent with ET-1 of 5.90 pg/mL or less was predictive of fewer cardiovascular events (odds ratio, 0.75; 95% confidence interval, 0.62-0.91). ET-1 reduction over time was associated with a lower rate of cardiovascular events compared with increasing or stable ET-1 (24.4% vs 50.0%).. ET-1 may be a unique predictor of HF prognosis, complementing other biomarkers in a multimarker profile. Serial measurement of ET-1 may provide additional prognostic information.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography; Endothelin-1; Female; Heart Failure, Systolic; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models

Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar.. Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]).. In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated.. Actelion Pharmaceuticals Ltd.

Topics: Aged; Chronic Disease; Double-Blind Method; Endothelin Receptor Antagonists; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Pyrimidines; Sulfonamides; Treatment Outcome; Vascular Resistance

Congestion is the main cause of morbidity in patients with heart failure. Treatment of fluid overload is often challenging in everyday clinical practice.. The aim of this study was to determine the diuretic effect of acetazolamide in patients with exacerbations of chronic heart failure, in addition to their stable diuretic therapy.. This was a single-center, unblinded study. Patients hospitalized with chronic heart failure exacerbations, with left ventricular ejection fraction (EF) < 50% and signs of volume overload, with a stable dose of diuretics anticipated by the attending physician over the next 4 days, were considered eligible for the study. On day 1, patients were randomized to receive acetazolamide orally, once daily (dose-adjusted to body weight) or no treatment (control group) as add-on diuretic therapy, on days 2 and 3. Diuresis, natriuresis, fluid balance, and symptoms were assessed daily, up to day 4.. Twenty patients (mean ± standard deviation age 72 ± 11.6 years; 85% men; mean EF 33.8 ± 11.4%; mean N-terminal pro-B-type natriuretic peptide 8064 ± 5593 pg/mL; mean intravenous furosemide dose 105 ± 55 mg) were enrolled. Diuresis, natriuresis, fluid balance, and symptoms were stable on days 1-4 in the control group. An increase in diuresis and natriuresis, and a greater change in fluid balance after administration of acetazolamide, were observed in patients randomized to acetazolamide. On day 4, there was a significant difference in fluid balance between the acetazolamide and control groups (-666 ± 1194 mL vs. +332 ± 705 mL; p = 0.035), and dyspnea was lower in patients receiving acetazolamide (visual scale, p < 0.001; 5-point Likert scale, 1.444 vs. 2.222; p = 0.04) CONCLUSIONS: In this pilot study, the addition of acetazolamide to the background diuretic regimen in patients with chronic heart failure exacerbations produced an additional diuretic effect and alleviation of dyspnea.

Topics: Acetazolamide; Administration, Intravenous; Aged; Aged, 80 and over; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Treatment Outcome; Ventricular Function, Left

Chronic heart failure (CHF), the final stage of various cardiovascular diseases, is a major public health problem resulting in significant hospitalization rates, mortality, and huge health care costs despite advances in the treatment and management of heart failure and heart failure-related risk factors. Qishen granules (QSG), a Chinese herbal formula, is widely used by traditional Chinese medicine (TCM) practitioners to treat CHF. Several animal experimental studies have showed that QSG can significantly relieve the heart failure symptoms in CHF rat models. However, there is as yet no standard clinical trial to confirm this. Thus, the investigators are conducting this study to evaluate the efficacy and safety of QSG in a large, and varied population.. This study is designed as a randomized, placebo-controlled, multi-center, double-blind clinical trial with parallel groups. A total of 200 patients with CHF will be recruited and randomly allocated to either the QSG treatment group or the placebo group (in a 1:1 ratio). The patients will receive QSG or placebo granules twice a day for 12 weeks. The primary outcome is the proportion of patients in the QSG group, compared with the placebo group, demonstrating a more than 30% decrease in NT-proBNP level during 12 weeks of treatment. The secondary outcomes consist of composite cardiac events, New York Heart Association functional classification, 6-minute walking distance, left ventricular ejection fraction, patient quality of life, and the TCM syndrome integral scale.. On a background of standard treatment, QSG may further reduce the levels of NT-proBNP. This trial will provide high-quality evidence on the efficacy and safety of QSG in treating CHF, thus providing reference for clinical application of QSG.. Clinical Trials.gov: NCT03027375 . Registered on 16 January 2017.

Topics: Biomarkers; Cardiovascular Agents; China; Chronic Disease; Clinical Protocols; Double-Blind Method; Drugs, Chinese Herbal; Exercise Tolerance; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Recovery of Function; Research Design; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Walk Test; Walking

To assess prognostic meaning of worsening renal failure (WRF) occurring during management of chronic heart failure (HF) with reduced ejection fraction.. When WRF develops during titration of HF medical therapy, it commonly leads to less aggressive care.. A total of 151 patients enrolled in a prospective, randomized study of standard of care (SOC) HF therapy versus SOC plus a goal N-terminal pro-B type natriuretic peptide (NT-proBNP) < 1000 pg/mL were examined. Cardiovascular (CV) event (defined as worsening HF, hospitalization for HF, significant ventricular arrhythmia, acute coronary or cerebral ischemia, or CV death) at 1 year relative to WRF (defined as any reduction in estimated glomerular filtration rate) 90 days postenrollment were tabulated.. Those developing WRF by 3 months had an average 14% reduction in estimated glomerular filtration rate. There was no difference in incidence of WRF between study arms (43% in SOC, 57% in NT-proBNP, P = .29). During the first 3 months of therapy titration, incident WRF was associated with numerically fewer CV events at 1 year compared with those without WRF (mean 0.81 vs 1.16 events, P = .21). WRF was associated trend toward fewer CV events in the SOC arm (hazard ratio 0.45, 95% confidence interval 0.16-1.24, P = .12); the NT-proBNP-guided arm had numerically lower CV event rates regardless of WRF. Subjects with NT-proBNP <1000 pg/mL and WRF received higher doses of guideline directed medical therapies, lower doses of loop diuretics, and had significantly lower CV event rates (P < .001).. Modest degrees of WRF are common during aggressive HF with reduced ejection fraction management, but we found no significant association with CV outcomes. HF care guided by NT-proBNP was not associated with more WRF compared with SOC, and led to benefit regardless of final renal function.

Topics: Aged; Analysis of Variance; Biomarkers; Chronic Disease; Cohort Studies; Disease Progression; Diuretics; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prospective Studies; Renal Insufficiency; Risk Assessment; Severity of Illness Index; Stroke Volume; Survival Analysis; Time Factors; Treatment Outcome

To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes.. LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was -0.8% (-2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P < 0.0001]. Serious cardiac events were seen in 12 (10%) patients treated with liraglutide compared with 3 (3%) patients in the placebo group (P = 0.04).. Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.

Topics: Acute Coronary Syndrome; Aged; Atrial Fibrillation; Chronic Disease; Diabetes Mellitus, Type 2; Disease Progression; Double-Blind Method; Echocardiography; Female; Heart Failure; Heart Rate; Humans; Incretins; Liraglutide; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Tachycardia, Ventricular; Treatment Outcome; Ventricular Function, Left; Walk Test

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan.. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial.. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Asian People; Biphenyl Compounds; Chronic Disease; Double-Blind Method; Drug Combinations; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Research Design; Single-Blind Method; Stroke Volume; Tetrazoles; Valsartan; Ventricular Function, Left

We have previously reported that a long-acting loop diuretic, azosemide, reduces cardiovascular risks in patients with chronic heart failure (CHF) as compared with a short-acting one, furosemide, in Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure (J-MELODIC). However, the mechanisms of the difference have not been elucidated. This study aimed to examine whether there is a difference in the reduction in plasma brain natriuretic peptide (BNP) level and in left ventricular (LV) functional recovery between the CHF patients treated with the long-acting diuretic (the azosemide group) and the short-acting diuretic (the furosemide group). We reviewed changes in plasma BNP level and echo-assessed LV functional parameters from baseline to a year after the entry in 288 CHF patients with New York Heart Association class II or III symptoms that joined J-MELODIC. The decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group (p < 0.01). The changes in echocardiographic parameters were not more favorable in the azosemide group than in the furosemide group. In conclusion, the decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group. These findings may account for the better prognosis in CHF patients treated with azosemide than those with furosemide in J-MELODIC.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Echocardiography; Female; Furosemide; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium Potassium Chloride Symporter Inhibitors; Sulfanilamides

Heart failure (HF) is a disease of neurohumoral dysfunction and current pharmacological therapies for HF have not improved mortality rates, thus requiring additional new strategies. Waon therapy for HF patients may be a complementary strategy with peripheral vasodilation via nitric oxide. We hypothesized that Waon therapy would improve neurohumoral factors, such as natriuretic peptides (NP) and the renin-angiotensin-aldosterone system (RAAS) in HF.Methods and Results:Plasma samples were collected from patients enrolled in the WAON-CHF Study (Waon therapy (n=77) or control (n=73)) before and after the treatment. B-type NP (BNP), C-type NP (CNP), and aldosterone (Aldo) levels were measured by respective specific radioimmunoassays. Although clinical parameters significantly improved in the Waon group compared with the control group, BNP, Aldo, and CNP levels were not statistically different between groups. On subanalysis with patient variables, BNP levels were improved in the Waon group treated with angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker or spironolactone. In addition, Aldo levels were improved in the Waon group patients with diabetes mellitus, hypertension, and inotrope use, and CNP levels were improved in Waon group patients with estimated glomerular filtration rate <60 mL/min/1.73 m. Waon therapy may accelerate the favorable actions of RAAS modulators in HF. (WAON-CHF Study: UMIN000006705).

Topics: Aldosterone; Case-Control Studies; Chronic Disease; Complementary Therapies; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Renin-Angiotensin System

Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N-Terminal B-type natriuretic peptide (NT-proBNP)-guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP-guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis.. The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged ≥60 years, left ventricular ejection fraction ≤45%, New York Heart Association functional class ≥I,I to NT-proBNP-guided versus symptom-guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP-guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced 1 and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) experienced ≥2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) experienced ≥2 events. NT-proBNP-guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P = .01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P = .35). This was not the case regarding HF hospitalization events (HR 0.85 [P = .14] vs HR 0.73 [P = .01]) The beneficial effect of NT-proBNP-guided therapy was seen only in patients aged <75 years, and not in those aged ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively).. NT-proBNP-guided therapy reduces the risk of recurrent events in patients <75 years of age. This included all-cause hospitalization by mainly reducing later events, adding knowledge to the neutral effect on this end point when shown using time-to-first-event analysis only.. isrctn.org, identifier: ISRCTN43596477.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Treatment Outcome

The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients.. Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control -0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training.. Low-dose exercise training at 4-7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results.

Topics: Analysis of Variance; Biomarkers; Cardiac Output; Chronic Disease; Exercise Test; Exercise Therapy; Exercise Tolerance; Female; Heart Rate; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Prospective Studies; Pulmonary Wedge Pressure; Thromboembolism; Treatment Outcome; Vascular Resistance; Ventricular Dysfunction, Right

To assess the usefulness of intrathoracic impedance monitoring (IIM) alerts in guiding empirical treatment of chronic heart failure (CHF) patients to prevent heart failure (HF) hospitalizations and unplanned HF care.. Chronic heart failure patients with OptiVol or CorVue capable implantable cardioverter-defibrillators were randomized to either the active group (IIM alarm turned on and diuretic dose increased by 50% for 1 week in the event of alarm sounding) or the control group (IIM alarm turned off). The primary endpoint was the number of HF hospitalizations per patient at 1 year. The NYHA class, 6MWT, B-type natriuretic peptide (BNP), and MLWHF questionnaire score were collected at baseline and follow-up. Eighty patients were included and 71 reached 1-year follow-up. There were 1.7 ± 1.5 alerts in the active group and 1.1 ± 1.0 in the control group, P = 0.07. In the active group, 61% of alerts led to a diuretic dose increase. There was a total of 11 HF hospitalizations in the active group vs. 6 in the control group without significant differences in the number of episodes per patient (0.3 ± 0.9 vs. 0.2 ± 0.4, P = 0.95). There were no unplanned HF visits in the active group vs. 0.1 ± 0.3 per patient in the control group, P = 0.08. The total MLWHF scores were significantly increased at the final follow-up in the control group, whereas a trend towards reduction was observed in the active group.. In this study, an empirical HF treatment guided by IIM alerts did not reduce emergency treatment of HF. However, it seems to have a positive impact on quality of life. CLINICAL TRIAL REGISTRATIONURL: http://www.clinicaltrials.gov. Unique identifier: NCT01320007.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiography, Impedance; Chronic Disease; Defibrillators, Implantable; Diuretics; Electric Countershock; Electric Impedance; Emergency Service, Hospital; Exercise Test; Exercise Tolerance; Female; Heart Failure; Hospitalization; Humans; London; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Quality of Life; Surveys and Questionnaires; Time Factors; Treatment Outcome

Patients with chronic heart failure (CHF) experience progressive deterioration of functional capacity and quality of life (QoL). This prospective, randomized, controlled trial assesses the effect of exercise training (ET) protocol on functional capacity, rehospitalization, and QoL in CHF patients older than 70 years compared with a control group. A total of 343 elderly patients with stable CHF (age, 76.90±5.67, men, 195, 56.9%) were randomized to ET (TCG, n=170) or usual care (UCG, n=173). The ET protocol involved supervised training sessions for 3 months in the hospital followed by home-telemonitored sessions for 3 months. Assessments, performed at baseline and at 3 and 6 months, included: ECG, resting echocardiography, NT-proBNP, 6-minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire, and comprehensive geriatric assessment with the InterRAI-HC instrument. As compared to UCG, ET patients at 6 months showed: i) significantly increased 6MWT distance (450±83 vs. 290±97 m, p=0.001); ii) increased ADL scores (5.00±2.49 vs. 6.94±5.66, p=0.037); iii) 40% reduced risk of rehospitalisation (hazard ratio=0.558, 95%CI, 0.326-0.954, p=0.033); and iv) significantly improved perceived QoL (28.6±12.3 vs. 44.5±12.3, p=0.001). In hospital and home-based telemonitored exercise confer significant benefits on the oldest CHF patients, improving functional capacity and subjective QoL and reducing risk of rehospitalisation.

Topics: Aged; Aged, 80 and over; Chronic Disease; Electrocardiography; Exercise; Exercise Test; Exercise Therapy; Female; Geriatric Assessment; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Concomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF.. This was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF ≤ 40%; NYHA class II-IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]).. On Day 21, significant increases were observed in the plasma biomarkers indicative of neprilysin and RAAS inhibition (ratio-to-baseline: cyclic guanosine monophosphate [cGMP], 1.38; renin concentration and activity, 3.50 and 2.27, respectively; all, P < 0.05). Plasma NT-proBNP levels significantly decreased at all the time points on Days 7 and 21; plasma aldosterone and endothelin-1 levels significantly decreased on Day 21 (all, P < 0.05). Following administration of LCZ696, the Cmax of sacubitril (neprilysin inhibitor prodrug), LBQ657 (active neprilysin inhibitor), and valsartan were reached within 0.5, 2.5, and 2 h. Between 100- and 200-mg doses, the Cmax and AUC0-12 h for sacubitril and LBQ657 were approximately dose-proportional while that of valsartan was less than dose-proportional.. Treatment with LCZ696 for 21 days was well tolerated and resulted in plasma biomarker changes indicative of neprilysin and RAAS inhibition in patients with HF. The pharmacokinetic exposure of the LCZ696 analytes in patients with HF observed in this study is comparable to that observed in the pivotal Phase III study.

Topics: Aged; Aldosterone; Aminobutyrates; Angiotensin Receptor Antagonists; Area Under Curve; Biomarkers; Biphenyl Compounds; Chronic Disease; Drug Administration Schedule; Drug Combinations; Endothelin-1; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System; Russia; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan; Ventricular Function, Left

Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain.. In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group.. Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

Topics: Aged; Aged, 80 and over; Chronic Disease; Diabetic Cardiomyopathies; Female; Heart Failure; Hot Temperature; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Steam Bath

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years.. Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429.. 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events.. Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers.. Bayer Pharma AG.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism; Pyrazoles; Pyrimidines; Time; Treatment Outcome; Young Adult

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was evaluated in Japanese patients with heart failure (HF) with reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. ARTS-HF Japan was a randomized, double-blind, phase 2b study. Patients (n=72) received oral, once-daily (o.d.) finerenone (2.5, 5, 7.5, 10 or 15 mg, up-titrated to 5, 10, 15, 20, or 20 mg, respectively, on day 30) or eplerenone (25 mg every other day, increased to 25 mg o.d. on day 30, and 50 mg on day 60) for 90 days. The primary endpoint was the proportion of individuals with a decrease of >30% in plasma NT-proBNP at day 90. Safety endpoints included the incidence of hyperkalemia. Decreases in NT-proBNP occurred in 23.1% of patients in the eplerenone group and 15.4%, 23.1%, 45.5%, 27.3% and 45.5% in the 2.5→5 mg, 5→10 mg, 7.5→15 mg, 10→20 mg and 15→20 mg finerenone groups, respectively (all P=NS). Mean changes in serum potassium levels were similar between groups.. Because of the small sample size, limited conclusions can be drawn. Considering the results of ARTS-HF and that finerenone was well tolerated in Japanese patients in ARTS-HF Japan, the safety and efficacy of finerenone should be further explored in a large outcomes trial including Japanese patients. (Circ J 2016; 80: 1113-1122).

Topics: Adult; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Hyperkalemia; Japan; Naphthyridines; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7-10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42-0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced distribution among all treatment groups.. Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial.

Topics: Aged; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

Chronic mitral regurgitation (MR) is characterized by adverse ventricular remodeling and progressive LV dysfunction leading to heart failure (HF). Beta-blockers (BB) improve LV remodeling and prognosis in patients with HF. As chronic severe MR results in neuroendocrine activation similar to HF, it is likely that BB may also exert favorable effects in these patients. No study has assessed the role of oral BB therapy in chronic rheumatic MR.. A total of 100 patients of chronic rheumatic MR (mean age 30±13.48 years, NYHA 2.2±0.5) were randomized to BB (Metoprolol, 37±13.5 mg, n=48) vs no BB (n=52) in addition to standard therapy.. Baseline BNP and echocardiographic parameters were comparable in the two groups. At 3 months, BB therapy resulted in significantly lower NYHA class (1.97 vs 2.35), BNP (141 vs 207 pg/mL), LV end-systolic (35.89 vs 51.30) and LV end-diastolic volumes (101 vs 128 mL/m(2) ), LV end-systolic stress (81.1 vs 93.3 dyn/cm(2) ), LV mass (122 vs 154 gm/m(2) ), and LV work (737.02 vs 952.82 mm Hg L/min, all P significant). Therapy with BB resulted in a -15.6%, -10.4%,-12.1%, and -7.3% reduction in LV end-systolic and end-diastolic dimensions and LVESVi and LVEDVi, respectively. Following BB therapy, BNP levels, end-systolic stress, indexed LV mass, and LV work also reduced significantly by 27.3%, 15.6%, 8.7%, and 28%, respectively. The control group had no significant change. The MR grade reduced from severe to moderate in 11% of those on BB (controls: no change). At 6 months, the BB group had further improvement in all echocardiographic parameters ranging from +9.1 to -18.2%.. In this first study of BB in rheumatic MR, targeting the sympatho-adrenergic axis exerted favorable effects on NYHA class, LV volumes, LV end-systolic stress, and LV work. Further studies are required to elucidate the role of BB in rheumatic MR.

Topics: Administration, Oral; Adolescent; Adrenergic beta-1 Receptor Antagonists; Adult; Biomarkers; Chronic Disease; Female; Heart; Humans; India; Male; Metoprolol; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Recovery of Function; Severity of Illness Index; Sympathetic Nervous System; Time Factors; Treatment Outcome; Ventricular Function, Left; Young Adult

Oxidative stress is a key element of the pathophysiology of heart failure (HF). As free thiols are readily oxidized by reactive oxygen and sulfur species, their circulating level may directly reflect the systemic redox status. This study addresses the role of serum free thiols in chronic HF, which is of particular interest as free thiols are amenable to therapeutic modulation and thus are a potential target for therapy. Free thiols were measured in serum of 101 previously characterized stable chronic HF patients (93% male, age 63.7±10.0y, left ventricular ejection fraction 34.6±8.2%), adjusted for total serum protein, and subsequently analysed for associations with clinical and outcome parameters. The mean serum free thiol concentration was 3.6±0.5μM/g protein. Patients with above-average levels were younger, had better renal function, lower levels of NT-proBNP and PTH, and higher levels of cholesterol. Furthermore, above-average levels were associated with favourable disease outcome, i.e. a decreased rehospitalisation rate and increased patient survival (HR 0.27 (95% CI 0.11-0.62), P=0.002) independent of associated clinical parameters, age and PTH. After adjustment for cholesterol or established prognostic factors in HF, eGFR and NT-proBNP the association was no longer significant, suggesting involvement of these variables in a common pathophysiological pathway. This exploratory study demonstrates favourable associations of serum free thiols with markers of HF severity and prognosis as well as disease outcome, which should be further investigated in larger prospective studies. Restoring redox status by therapeutic modulation of free thiols may be a promising strategy to improve disease outcome in CHF.

Topics: Aged; Biomarkers; Chronic Disease; Double-Blind Method; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Severity of Illness Index; Sulfhydryl Compounds

To investigate the effects of catheter ablation and rate control strategies on cardiac and inflammatory biomarkers in patients with heart failure and persistent atrial fibrillation (AF).. Patients were recruited from the ARC-HF trial (catheter Ablation vs Rate Control for management of persistent AF in Heart Failure, NCT00878384), which compared ablation with rate control for persistent AF in heart failure. B-type natriuretic peptide (BNP), midregional proatrial natriuretic peptide (MR-proANP), apelin, and interleukin-6 (IL-6) were assayed at baseline, 3 months, 6 months, and 12 months. The primary end point, analyzed per-protocol, was changed from baseline at 12 months.. Of 52 recruited patients, 24 ablation and 25 rate control subjects were followed to 12 months. After 1.2 ± 0.5 procedures, sinus rhythm was present in 22 (92%) ablation patients; under rate control, rate criteria were achieved in 23 (96%) of 24 patients remaining in AF. At 12 months, MR-proANP fell significantly in the ablation arm (-106.0 pmol/L, interquartile range [IQR] -228.2 to -60.6) compared with rate control (-28.7 pmol/L, IQR -69 to +9.5, P = 0.028). BNP showed a similar trend toward reduction (P = 0.051), with no significant difference in apelin (P = 0.13) or IL-6 (P = 0.68). Changes in MR-proANP and BNP correlated with peak VO2 and ejection fraction, and MR-proANP additionally with quality-of-life score.. Catheter ablation, compared with rate control, in patients with heart failure and persistent AF was associated with significant reduction in MR-proANP, which correlated with physiological and symptomatic improvement. Ablation-based rhythm control may induce beneficial cardiac remodeling, unrelated to changes in inflammatory state. This may have prognostic implications, which require confirmation by event end point studies.

Topics: Anti-Arrhythmia Agents; Apelin; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Cardiac Pacing, Artificial; Catheter Ablation; Chronic Disease; Female; Heart Failure; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome

Topics: Biomarkers; Body Mass Index; Cachexia; Chronic Disease; Echocardiography; Endothelin-1; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Time Factors; Troponin I; Weight Loss

Brain natriuretic peptide (BNP) is the most effective predictor of outcomes in chronic heart failure (CHF). This study sought to determine the qualitative relationship between the BNP levels at discharge and on the day of cardiovascular events in CHF patients. We devised a mathematical probabilistic model between the BNP levels at discharge (y) and on the day (t) of cardiovascular events after discharge for 113 CHF patients (Protocol I). We then prospectively evaluated this model on another set of 60 CHF patients who were readmitted (Protocol II). P(t|y) was the probability of cardiovascular events occurring after >t, the probability on t was given as p(t|y) = -dP(t|y)/dt, and p(t|y) = pP(t|y) = αy

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Models, Cardiovascular; Natriuretic Peptide, Brain; Predictive Value of Tests

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Body Mass Index; Chronic Disease; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Obesity; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Protease Inhibitors; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown.. 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01).. NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chronic Disease; Disease Management; Dizziness; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Quality of Life; Renal Insufficiency; Surveys and Questionnaires; Treatment Outcome

Adaptive servo-ventilation (ASV) therapy is expected to be novel nonpharmacotherapy with hemodynamic effects on patients with chronic heart failure (CHF), but sufficient evidence has not been obtained.. A 24-week, open-label, randomized, controlled study was performed to confirm the cardiac function-improving effect of ASV therapy on CHF patients. At 39 institutions, 213 outpatients with CHF, whose left ventricular ejection fraction (LVEF) was <40% and who had mild to severe symptoms [New York Heart Association (NYHA) class: ≥II], were enrolled. After excluding 8 patients, 102 and 103 underwent ASV plus guideline-directed medical therapy (GDMT) [ASV group] and GDMT only [control group], respectively. The primary endpoint was LVEF, and the secondary endpoints were HF deterioration, B-type natriuretic peptide (BNP), and clinical composite response (CCR: NYHA class+HF deterioration). LVEF and BNP improved significantly at completion against the baseline values in the 2 groups. However, no significant difference was found between these groups. HF deterioration tended to be suppressed. The ASV group showed a significant improvement in CCR corroborated by significant improvements in NYHA class and ADL against the control group.. Under the present study's conditions, ASV therapy was not superior to GDMT in the cardiac function-improving effect but showed a clinical status-improving effect, thus indicating a given level of clinical benefit.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Respiration, Artificial; Stroke Volume

To observe the changes of serum heart-type fatty acid-binding protein (h-FABP) and brain natriuretic peptide (BNP) in children with chronic heart failure (CHF) and evaluate the effects of carvedilol.. A total of 36 patients with CHF, including 17 of endocardial fibroelastosis and 19 of dilated cardiomyopathy, were enrolled and were randomly divided into a carvedilol treatment group (group A) and a conventional treatment group (group B). Group A (n = 16) was treated with carvedilol and conventional treatment and group B (n = 20) was managed with conventional treatment only. Thirty healthy children were enrolled as controls. The concentrations of serum h-FABP and BNP were measured by enzyme-linked immunosorbent assay, and the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and cardiac index (CI) were measured by echocardiography.. The concentrations of serum h-FABP and BNP in patients with CHF were significantly higher than in the control group (21.7 ± 4.3 ng/mL vs. 6.3 ± 1.7 ng/mL, 582.4 ± 180.6 pg/mL vs.31.2 ± 9.8 pg/mL, all P < 0.01), positively correlated with the degree of heart failure (all P < 0.01), and were both higher in groups endocardial fibroelastosis and dilated cardiomyopathy than in the control group (all P < 0.01), but there was no statistically significant difference between the 2 groups (P > 0.05). h-FABP concentration in patients with CHF was positively correlated with BNP (r = 0.78, P < 0.01) but negatively correlated with LVEF, LVFS, and CI (r = -0.65, -0.64, and -0.71, respectively; all P < 0.01). BNP concentration was also negatively correlated with LVEF, LVFS, and CI (r = -0.75, -0.61, and -0.79, respectively; all P<0.01). After treatment with carvedilol, the serum concentrations of h-FABP and BNP in group A were lower than in group B, and the magnitude of heart rate reduction, improvement of LVEF, LVFS, and CI, and reduction of left ventricular end-systolic diameter and left ventricular end-diastolic diameter in group A were all greater than in group B (all P < 0.01). Treatment with carvedilol had no adverse events.. Serum concentrations of h-FABP and BNP can be used as biomarkers to evaluate the severity of heart failure, and carvedilol can significantly improve heart function in children with CHF.

Topics: Adrenergic beta-Antagonists; Age Factors; Biomarkers; Carbazoles; Carvedilol; Child; Child, Preschool; China; Chronic Disease; Echocardiography; Enzyme-Linked Immunosorbent Assay; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Heart Failure; Humans; Infant; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Predictive Value of Tests; Propanolamines; Severity of Illness Index; Stroke Volume; Treatment Outcome; Ventricular Function, Left

The aim of this study was to evaluate the effectiveness of umbilical cord mesenchymal stem cells (MSCs) in the treatment of chronic systolic heart failure. Fifty-nine hospitalized patients with heart failure were randomly divided into a treatment group (30 patients) and a control group (29 patients). The treatment group received treatment with medication as well as intracoronary transplantation of umbilical cord MSCs, and the control group, only medication. The cardiac structure, function change, and rehospitalization and mortality rates of the 2 groups were observed before and 1 and 6 months after treatment. One month after the transplantation of umbilical cord MSCs, the incidence of fatigue, chest tightness, and dyspnea was high in the treatment group. The 6-min walking distance of the treatment group was found to be significantly higher than that of the control group (P < 0.05); in addition, the NT-proBNP level, left ventricular ejection fraction, and mortality rate of the treatment group were statistically lower than those of the control group (P < 0.05). Readmission rates showed a downward trend, but the difference was not statistically significant (P > 0.05). Using umbilical cord MSCs in the treatment of congestive heart failure can help improve cardiac remodeling and cardiac function and reduce the mortality rate.

Topics: Adult; Aged; Case-Control Studies; Chronic Disease; Female; Heart Failure, Systolic; Heart Function Tests; Humans; Male; Mesenchymal Stem Cell Transplantation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Recovery of Function; Umbilical Cord; Young Adult

Acute exacerbation is a common cause of hospitalization in patients with chronic heart failure, and coronary heart disease is the most common cause. Shenfu injection, a Traditional Chinese Medicine injection, widely used in the adjuvant treatment of patients with acute exacerbation of chronic heart failure, shows some treatment effect in improving the symptoms and the quality of life, but it lacks the rigorous clinical evaluation of research reports. This paper describes the protocol for the clinical assessment of Shenfu injection loading in the treatment of patients with acute exacerbation of chronic heart failure.. This protocol adopts the design of a prospective, randomized, multicenter, blind imitation, placebo-controlled trial to assess the efficacy and safety of Shenfu injection loading in the treatment of patients with acute exacerbation of chronic heart failure due to coronary heart disease. The research will be carried out in 12 hospitals in China and is expected to enroll 160 inpatients with acute exacerbation of chronic heart failure due to coronary heart disease (yang and qi deficiency syndrome). On the basis of the conventional therapy of western medicine, patients will be randomized to either the treatment group (100 ml 5% glucose injection + 50 ml Shenfu injection) or the control group (150 ml 5% glucose injection) for 7 ± 1 days and follow-up for 28 ± 3 days. The primary outcomes are New York Heart Association cardiac function classification and Traditional Chinese Medicine syndromes. The secondary outcomes are left ventricular ejection fraction, brain natriuretic peptide level, Lee's heart failure score, 6-minute walking distance, and the incidence and readmission rate of cardiovascular events (including the emergency rate due to acute exacerbation of chronic heart failure).. This trial will assess the effect of loading Shenfu injection in the treatment of patients with acute exacerbation of chronic heart failure caused by coronary heart disease (yang-qi deficiency syndrome) on the symptoms and signs of heart failure, exercise tolerance, and other aspects, and observe its influence on the short-term prognosis with follow-up. The results of the study will provide clinical research evidence for application of Shenfu injection in the treatment.. This trial was registered on 26 December 2012 at the Chinese Clinical Trials Register (Identifier: ChiCTR-TRC-12002857 ).

Topics: Adult; Aged; Biomarkers; Cardiovascular Agents; China; Chronic Disease; Clinical Protocols; Coronary Disease; Disease Progression; Drugs, Chinese Herbal; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Injections; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Pilot Projects; Prospective Studies; Recovery of Function; Research Design; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Walking

Tβ4 is an integral factor in repair of myocardium in animal models. To investigate whether Tβ4 is important in human cardiac disease and has a role in mediating the beneficial cardiac effects of bone-marrow-derived stem cell (BMSC) therapy, we measured serial plasma Tβ4 levels in patients enrolled on the REGENERATE-IHD cell therapy trial.. Plasma Tβ4 concentrations were measured in 13 patients who received BMSCs and 14 controls.. There was a significant increase in plasma Tβ4 in the BMSC group 24 h after intracardiac injection. Increases in Tβ4 levels were associated with improvement in New York Heart Association symptom class.. This exploratory study highlights the need for further study of Tβ4 in human cardiovascular disease.

Topics: Aged; Bone Marrow Cells; Cell Count; Chronic Disease; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Stem Cell Transplantation; Thymosin; Treatment Outcome

Current heart failure (HF) risk prediction models do not consider how individual patient assessments occur in incremental steps; furthermore, each additional diagnostic evaluation may add cost, complexity, and potential morbidity.. Using a cohort of well-treated ambulatory HF patients with reduced ejection fraction who had complete clinical, laboratory, health-related quality of life, imaging, and exercise testing data, we estimated incremental prognostic information provided by 5 assessment categories, performing an additional analysis on those with available N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. We compared the incremental value of each additional assessment (quality of life screen, laboratory testing, echocardiography, and exercise testing) to baseline clinical assessment for predicting clinical outcomes (all-cause mortality, all-cause mortality/hospitalization, and cardiovascular death/HF hospitalizations), gauging incremental improvements in prognostic ability with more information using area under the curve and reclassification improvement (net reclassification index), with and without NT-proBNP availability. Of 2331 participants, 1631 patients had complete clinical data; of these, 1023 had baseline NT-proBNP. For prediction of all-cause mortality, models with incremental assessments sans NT-proBNP showed improvements in C-indices (0.72 [clinical model alone]-0.77 [complete model]). Compared with baseline clinical assessment alone, net reclassification index improved from 0.035 (w/laboratory data) to 0.085 (complete model). These improvements were significantly attenuated for models in the subset with measured NT-proBNP data (c-indices: 0.80 [w/laboratory data]-0.81 [full model]); net reclassification index improvements were similarly marginal (0.091→0.096); prediction of other clinical outcomes had similar findings.. In chronic HF patients with reduced ejection fraction, the marginal benefit of complex prognostic evaluations should be weighed against potential patient discomfort and cost escalation.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Topics: Aged; Biomarkers; Cause of Death; Chronic Disease; Diagnostic Techniques, Cardiovascular; Echocardiography; Exercise Test; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Quality of Life; Risk Assessment; Risk Factors; Stroke Volume; Surveys and Questionnaires; Ventricular Function, Left

We aimed to elucidate the prognostic impact of anemia with special reference to the clinical background of patients with chronic heart failure (CHF).. We examined 4,646 consecutive patients with Stage C/D CHF registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). Among them, 1,627 (35%) had anemia and were characterized by higher age (74 vs. 66 years), lower estimated glomerular filtration rate (52.8 vs. 66.1 ml/min/1.73 m(2)) and higher B-type natriuretic peptide levels (154.5 vs. 81.8 pg/ml) (all P<0.001) but comparable left ventricular ejection fraction (LVEF; 57.5 vs. 56.7%). Anemic patients were more frequently treated with diuretics (55.1 vs. 42.3%) but less often treated with β-blockers (45.4 vs. 51.1%) (both P<0.001). During a median follow-up of 3.8 years, 371 and 272 patients died with and without anemia, respectively (22.8 vs. 9.0%, adjusted hazard ratio 1.40; 95% confidence interval 1.15-1.71, P=0.001). Subgroup analysis revealed that the prognostic impact of anemia was comparable in terms of age, sex, renal function and double product, but differed by LVEF level and CHF etiology (both, P for interaction <0.001). In particular, a difference in the prognostic impact of LVEF level was noted in patients with ischemic heart disease.. These results indicate that the prognostic impact of anemia is evident in CHF patients with preserved EF and it differs by CHF etiology.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Anemia; Chronic Disease; Disease-Free Survival; Diuretics; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Survival Rate

Worsening chronic heart failure (HF) is a major public health problem.. To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF).. Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic.. Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks.. The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point.. Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively.. Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF.. clinicaltrials.gov Identifier: NCT01951625.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Guanylate Cyclase; Heart Failure; Heterocyclic Compounds, 2-Ring; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pyrimidines; Treatment Outcome; Ventricular Dysfunction, Left

Chronic heart failure is a crucial problem of current cardiology. Despite that, no major development has occurred in the therapy in recent years. In this regard, first results of studies with ARNI inhibitors (angiotensin-receptor neprilysin inhibitors) may be considered hopeful. Dual inhibition of AT1 receptors and neprilysin blocks renin-angiotensin-aldosteron (RAS) axis and concurrently supports natural vasodilatory and diuretic effect of natriuretic peptides. Large-scale prospective randomized multicenter trial PARADIGM-HF with more than 8000 individuals with stabilized chronic heart failure with systolic dysfunction (LV EF 40%, later 35%), mostly in functional class NYHA II-III with elevated BNP/NT-pro BNP has shown 20% decrease in primary endpoint (cardiovascular death or hospitalization for heart failure) in a group treated by ARNI (LCZ696; sacubiltril - valsartan). Beneficial effect of ARNI was consistent also for total and cardiovascular mortality, for hospitalization for heart failure and in other pre-specified subgroup analyses, including quality of life. The treatment was safe, typical adverse event was hypotension, however without a need to interrupt the treatment. Dual RAS and neprilysin inhibition might thus after long time become a change in stable chronic heart failure with systolic dysfunction treatment "paradigm". Czech Republic significantly contributed to this study and all study sites should be congratulated and thanked for their high-quality work provided.

Topics: Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Biphenyl Compounds; Cardiotonic Agents; Chronic Disease; Czech Republic; Drug Combinations; Female; Humans; Male; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Prospective Studies; Survival Rate; Tetrazoles; Valsartan; Ventricular Dysfunction, Left

Mineralocorticoid receptor antagonist (MRA) use in acutely decompensated chronic heart failure (ADCHF) may improve congestion through diuretic effect and prevent neurohormonal activation. We aimed to evaluate the clinical effect and safety of spironolactone in ADCHF.. Prospective, experimental, single-center, and single-blinded trial. Patients were treated with: standard ADCHF therapy or oral spironolactone 50-100mg/d plus standard ADCHF therapy.. During a 1year period, 100 patients were enrolled, 50 included in the treatment group. Mean (SD) spironolactone dose (mg) at day 1 was 94.5±23.3 and at day 3 was 62.7±24.3. Worsening renal function (increase in pCr≥0.3mg/dL from day 1 to day 3) was more likely to occur in control group (20% vs. 4%; p=0.038), serum potassium did not differ between groups, and plasma NTproBNP had a significant decrease in spironolactone group at day 3 (median [IQR], 2488 [4579] vs. 1555 [1832]; p=0.05). Furthermore, a greater proportion of patients in the treatment group were free of congestion at day 3: less edema, rales, jugular venous pressure (JVP) and orthopnea (all, p<0.05). In addition, a significantly higher proportion of patients were on oral furosemide at day 3 (44% vs. 82%; p<0.001).. Our study supports the safety of high dose spironolactone in ADCHF and suggests a positive impact in the resolution of congestion. The important findings of our pilot study need to be confirmed in larger trials.

Topics: Acute Disease; Aged; Aged, 80 and over; Chronic Disease; Disease Progression; Diuretics; Edema; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Potassium; Pulmonary Edema; Renal Insufficiency; Single-Blind Method; Spironolactone; Treatment Outcome

The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study.. Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (≥60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality.. Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Biomarkers; C-Reactive Protein; Chronic Disease; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Pyrimidines; Risk Factors; Rosuvastatin Calcium; Sensitivity and Specificity; Stroke; Sulfonamides; Survival Rate; Troponin T

Most patients with heart failure are diagnosed and managed in primary care, however, underdiagnosis and undertreatment are common. We assessed whether implementation of a diagnostic-therapeutic strategy improves functionality, health-related quality of life, and uptake of heart failure medication in primary care.. A selective screening study followed by a single-blind cluster randomized trial in primary care. The study population consists of patients aged 65 years or over who presented themselves to the general practitioner in the previous 12 months with shortness of breath on exertion. Patients already known with established heart failure, confirmed by echocardiography, are excluded. Diagnostic investigations include history taking, physical examination, electrocardiography, and serum N-terminal pro B-type natriuretic peptide levels. Only participants with an abnormal electrocardiogram or an N-terminal pro B-type natriuretic peptide level exceeding the exclusionary cutpoint for non-acute onset heart failure (> 15 pmol/L (≈ 125 pg/ml)) will undergo open-access echocardiography. The diagnosis of heart failure (with reduced or preserved ejection fraction) is established by an expert panel consisting of two cardiologists and a general practitioner, according to the criteria of the European Society of Cardiology guidelines.Patients with newly established heart failure are allocated to either the 'care as usual' group or the 'intervention' group. Randomization is at the level of the general practitioner. In the intervention group general practitioners receive a single half-day training in heart failure management and the use of a structured up-titration scheme. All participants fill out quality of life questionnaires at baseline and after six months of follow-up. A six-minute walking test will be performed in patients with heart failure. Information on medication and hospitalization rates is extracted from the electronic medical files of the general practitioners.. This study will provide information on the prevalence of unrecognized heart failure in elderly with shortness of breath on exertion, and the randomized comparison will reveal whether management based on a half-day training of general practitioners in the practical application of an up-titration scheme results in improvements in functionality, health-related quality of life, and uptake of heart failure medication in heart failure patients compared to care as usual.. ClinicalTrials.gov NCT01202006.

Topics: Aged; Aged, 80 and over; Attitude of Health Personnel; Biomarkers; Cardiovascular Agents; Chronic Disease; Clinical Protocols; Dyspnea; Echocardiography; Education, Medical, Continuing; Electrocardiography; Exercise Test; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Practice Patterns, Physicians'; Predictive Value of Tests; Prevalence; Primary Health Care; Quality of Life; Recognition, Psychology; Research Design; Single-Blind Method; Stroke Volume; Surveys and Questionnaires; Treatment Outcome; Ventricular Function, Left

This analysis aimed to perform a head-to-head comparison of 3 of the promising biomarkers of cardiovascular (CV) outcomes in heart failure (HF)-soluble ST2 (sST2), growth differentiation factor (GDF)-15, and highly-sensitive troponin T (hsTnT)-and to evaluate the role of serial measurement of these biomarkers in patients with chronic HF.. sST2, GDF-15, and hsTnT are strongly associated with CV outcomes in HF.. This post-hoc analysis used data from a study in which 151 patients with chronic HF due to left ventricular systolic dysfunction were followed up over 10 months. At each visit, N-terminal pro-B-type natriuretic peptide (NT-proBNP), sST2, GDF-15, and hsTnT were measured and any major CV events were recorded.. Baseline values of all 3 novel biomarkers independently predicted total CV events even after adjusting for clinical and biochemical characteristics, including NT-proBNP, with the best model including all 3 biomarkers (p < 0.001). Adding serial measurement to the base model appeared to improve the model's predictive ability (with sST2 showing the most promise), but it is not clear whether this addition is a unique contribution. However, when time-dependent factors were included, only sST2 serial measurement independently added to the risk model (odds ratio: 3.64; 95% confidence interval: 1.37 to 9.67; p = 0.009) and predicted reverse myocardial remodeling (odds ratio: 1.22; 95% confidence interval: 1.04 to 1.43; p = 0.01).. In patients with chronic HF, baseline measurement of novel biomarkers added independent prognostic information to clinical variables and NT-proBNP. Only serial measurement of sST2 appeared to add prognostic information to baseline concentrations and predicted change in left ventricular function. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting (PROTECT)]; NCT00351390).

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Receptors, Cell Surface; Risk Assessment; Treatment Outcome; Troponin T; Ventricular Dysfunction, Left; Ventricular Remodeling

In primary care the diagnosis of CHF and ECF accumulation is no triviality. We aimed to predict plasma BNP, CHF and ECF accumulation with segmental impedance spectroscopy while using and extending the electrodes of the conventional electrocardiography.. Three combined multiple electrodes were added to the 15 lead ECG for segmental impedance spectroscopy and for measuring the maximal rate of segmental fluid volume change with heart action at the thorax and the legs. The obtained signals were analyzed by partial correlation analyses in comparison with plasma BNP, CHF classes, ejection fraction by echocardiography and cardiac index by double gas re-breathing. 119 subjects (34 healthy volunteers, 50 patients with CHF, NYHA classes II to IV and 35 patients without CHF) were investigated.. The maximal rate of volume change with heart action at the thorax and at the legs, as well as the ECF/ICF ratio at the legs contribute equally and independently to the prediction of BNP and heart failure in an unknown test sample of 49 patients (multiple r=0.88, p<0.001). The ROC-curve for the predicted plasma BNP>400 pg/ml gave an AUC=0.93. The absence or the presence of heart failure could be predicted correctly by a binomial logistic regression in 92.9 and 87.5% of cases, respectively.. The methodology, which is based on inverse coupling of BNP release and of maximal blood acceleration and on sensitive detection of ECF overload, could enable the diagnosis of CHF with useful sensitivity and specificity while writing a routine-ECG.

Topics: Adult; Aged; Algorithms; Cardiography, Impedance; Chronic Disease; Diagnosis, Computer-Assisted; Electroencephalography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Water-Electrolyte Imbalance

The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure.. The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown.. HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP.. After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure.. Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.

Topics: Aged; Biomarkers; Cause of Death; Chronic Disease; Death, Sudden, Cardiac; Female; Fibrosis; Galectin 3; Heart Failure, Systolic; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Receptors, Cell Surface; Risk Factors; Stress, Physiological; Ventricular Dysfunction, Left

In the prospective, open-label multicenter INTENSIFY study, the effectiveness and tolerability of ivabradine as well as its impact on quality of life (QOL) in chronic systolic heart failure (CHF) patients were evaluated over a 4-month period.. In CHF patients with an indication for treatment with ivabradine, resting heart rate (HR), heart failure symptoms [New York Heart Association (NYHA) class, signs of decompensation], left ventricular ejection fraction, brain natriuretic peptide (BNP) values, QOL, and concomitant medication with focus on beta-blocker therapy were documented at baseline, after 4 weeks, and after 4 months. The results were analyzed using descriptive statistical methods.. Thousand nine hundred and fifty-six patients with CHF were included. Their mean age was 67 ± 11.7 years and 56.9% were male. 77.8% were receiving beta-blockers. Other concomitant medications included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (83%), diuretics (61%), aldosterone antagonists (18%), and cardiac glycosides (8%). At baseline, the mean HR of patients was 85 ± 11.8 bpm, 51.1% and 37.2% of patients were classified as NYHA II and III, respectively, and 22.7% showed signs of decompensation. BNP concentrations were tracked in a subgroup, and values exceeding 400 pg/mL were noted in 53.9% of patients. The mean value of the European quality of life-5 dimensions (EQ-5D) QOL index was 0.64 ± 0.28. After 4 months of treatment with ivabradine, HR was reduced to 67 ± 8.9 bpm. Furthermore, the proportion of patients presenting with signs of decompensation decreased to 5.4% and the proportion of patients with BNP levels >400 pg/mL dropped to 26.7%, accompanied by a shift in NYHA classification towards lower grading (24.0% and 60.5% in NYHA I and II, respectively). EQ-5D index improved to 0.79 ± 0.21.. Over 4 months of treatment, ivabradine effectively reduced HR and symptoms in CHF patients in this study reflecting daily clinical practice. These benefits were accompanied by improved QOL and good general tolerability.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiovascular Agents; Chronic Disease; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Quality of Life; Treatment Outcome

As complex disease, heart failure is associated with various pathophysiological and biochemical disorders. No single biomarker is able to display all these characteristics. Therefore, we evaluated a multimarker panel together with the biochemical gold-standard NT-proBNP. Part of the panel are markers for angiogenesis (Endostatin, IBP-4, IBP-7, sFlt-1 as antiangiogenetic factors and PLGF as angiogenectic factor), myocyte stress (GDF-15), extracellular matrix remodelling (galectin-3, mimecan and TIMP-1), inflammation (galectin-3) and myocyte injury (hs-TnT).. All markers (Roche Diagnostics, Penzberg, Germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls.. All markers were positively correlated with ln NT-proBNP (each p < 0.05). Furthermore, they were significantly elevated in patients with chronic heart failure (each p < 0.05). All markers increased significantly with severity of LV dysfunction and severity of New York Heart Association class (each p < 0.05), except for PLGF and Mimecan (each p = NS). With the exception of endostatin, mimecan and PLGF, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. In a multimarker approach of the five biomarkers with the best performance (NT-proBNP, hs-TnT, TIMP-1, GDF-15 and IBP-4), the event rate was superior to NT-proBNP alone and increased significantly and progressively with the number of elevated biomarkers.. All emerging markers increased stepwise with the severity of symptoms and LV dysfunction and offer important prognostic information in chronic heart failure, except for PLGF and mimecan. Five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. Prognostication in heart failure may be further improved through a multimarker approach.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Proteins; Chronic Disease; Endostatins; Female; Follow-Up Studies; Galectin 3; Galectins; Growth Differentiation Factor 15; Heart Failure; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Placenta Growth Factor; Pregnancy Proteins; Prognosis; Survival Rate; Tissue Inhibitor of Metalloproteinase-1; Troponin T; Vascular Endothelial Growth Factor Receptor-1; Ventricular Dysfunction, Left

This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF).. CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints.. Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis.. A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028).. Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).

Topics: Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ubiquinone; Vitamins

The aim of this study was to explore the role of immune modulation therapy in regulating the imbalance of Th1/Th2, serum IFN-γ, IL-4 and the T-cell-specific transcription factors T-bet/GATA-3 in peripheral blood in aging male patients with chronic cardiac insufficiency (CCI).. In total, 156 participants were divided into three groups: the CCI intervention group, which received regular therapy and thymopetidum (20 mg intramuscular injection, once every other day for 3 months; n = 70), the CCI control group, which received regular therapy (n = 56) and 50 healthy individuals older than 57 years of age, who served as normal controls.. Before therapy, in comparison with the control group, levels of left ventricular end diastolic diameter, NT-proBNP, C-reactive protein (CRP), Th1, Th1/Th2, IFN-γ, and T-bet mRNA and T-bet/GATA-3 mRNA all increased, and the level of left ventricular ejection fraction (LVEF), 6MWT, Th2, IL-4, and GATA-3 mRNA also decreased in both the CCI intervention and control groups. Linear correlation analysis indicated that LVEF was inversely correlated with serum NT-proBNP, CRP, Th1/Th2, IFN-γ and T-bet mRNA/GATA-3 mRNA, and was positively correlated with plasma IL-4. After 3 months of therapy, levels of left ventricular end diastolic diameter, NT-proBNP, CRP, Th1, Th1/Th2, IFN-γ, T-bet mRNA and T-bet/GATA-3 mRNA decreased in the two CCI subgroups, but levels in the CCI intervention group were lower in comparison to the control group. Levels of LVEF, 6MWT, Th2 and GATA-3 mRNA increased in the two CCI subgroups, while levels in the CCI intervention group were higher in comparison with the control group. Plasma levels of IL-4 showed no change after treatment.. Immune modulation improved cardiac function of CCI patients and was associated with amelioration of T-helper superficial transcription factor polarization and its related cytokine imbalance. Immune modulation might be a new treatment strategy for aging CCI patients.

Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; C-Reactive Protein; Chronic Disease; Echocardiography; Flow Cytometry; GATA3 Transcription Factor; Gene Expression; Heart Failure; Humans; Interferon-gamma; Interleukin-4; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; T-Box Domain Proteins; Th1 Cells; Th2 Cells; Thymopentin; Treatment Outcome

Chronic heart failure (CHF) is an increasingly common cardiovascular disease despite recent advances in its diagnosis and management.. A multicenter, open-label study was designed to assess the efficacy and safety of 60-week treatment with candesartan in Japanese patients with mild to moderate CHF. Primary efficacy endpoints were changes from baseline in plasma brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), end-diastolic dimension, and New York Heart Association (NYHA) functional class. Two hundred and eighty-nine eligible patients were divided into 2 groups based on the daily dose at the end of treatment: high-dose (HD, 8mg, N=170) and low-dose (LD, 2 or 4mg, N=119). Neither plasma BNP levels nor LVEF changed from the baseline to the end of treatment in the LD group, whereas BNP significantly improved from 61.6 to 50.1pg/mL (p=0.0005) and LVEF from 57.2 to 60.1% (p=0.0005) in the HD group. The changes in NYHA functional class were comparable between groups: 21.2% improved and 76.3% unchanged in the LD group and 20.6% improved and 79.4% unchanged in the HD group. No safety concerns were observed in either group.. HD candesartan was more effective in improving plasma BNP levels and cardiac function than LD in Japanese CHF patients. Both LD and HD candesartan were well tolerated in CHF patients.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Asian People; Benzimidazoles; Biomarkers; Biphenyl Compounds; Chronic Disease; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index; Stroke Volume; Tetrazoles; Time Factors

Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients.. Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥ 18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥ 40 mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event.. Unique identifier: NCT01646515.

Topics: Biomarkers; Cardiovascular Agents; Chronic Disease; Clinical Protocols; Double-Blind Method; Drug Administration Schedule; Exercise Test; Exercise Tolerance; Heart Failure, Systolic; Hemodynamics; Hospitalization; Humans; Natriuretic Peptide, Brain; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Prospective Studies; Pyrimidines; Recovery of Function; Republic of Korea; Research Design; Stroke Volume; Sulfonamides; Systole; Time Factors; Treatment Outcome; Ventricular Function, Left

The relationship between changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic or clinical definitions of response to cardiac resynchronization therapy (CRT) has not been evaluated. The aims of the present evaluation were to assess: (1) the relationship between changes in NT-proBNP after 6 months of CRT and clinical and echocardiographic responses; (2) the association between NT-proBNP changes and long-term outcome.. In 170 patients treated with CRT (age 61 ± 11 years, 75% male), clinical and echocardiographic parameters and circulating NT-proBNP levels were assessed at baseline and 6 months after CRT. At 6 months follow-up, improvement in New York Heart Association class ≥ 1 point, decrease in left ventricular end-systolic volume ≥ 15%, and decrease in NT-proBNP ≥ 15% defined clinical, echocardiographic, and neurohormonal CRT response, respectively. All-cause mortality data were collected and related to neurohormonal response.. Neurohormonal, echocardiographic, and clinical response rates were 54%, 58%, and 66%, respectively. The majority of patients (71%) showing echocardiographic response had NT-proBNP reduction ≥ 15%. In contrast, only 58% of patients who showed clinical response also had NT-proBNP reduction ≥ 15%. During a median follow-up of 32 months, 40 patients died. Patients with neurohormonal response demonstrated a superior long-term outcome compared to patients without neurohormonal response (log-rank P = 0.02).. NT-proBNP reduction ≥ 15% showed better agreement with echocardiographic response compared to clinical response. Neurohormonal response was associated with superior long-term outcome compared to insufficient reduction in NT-proBNP levels.

Topics: Biomarkers; Cardiac Resynchronization Therapy; Chronic Disease; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Neurotransmitter Agents; Peptide Fragments; Prevalence; Prognosis; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Survival Rate; Treatment Outcome; Ventricular Remodeling

To examine the effect of balloon pulmonary angioplasty (BPA) on chronic thromboembolic pulmonary hypertension (CTEPH) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy.. Observational cohort study.. Referred patients with inoperable or persistent CTEPH.. Twenty consecutive CTEPH patients (10 females), aged 60±10 years.. Right heart catheterisation, functional capacity (cardiopulmonary exercise testing (CPET) and NYHA class) and blood sampled biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA.. Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries. Two deaths occurred following the first BPA, with an overall 10% periprocedural death rate. Reperfusion oedema complicated seven procedures. Comparisons before and after BPA showed significant haemodynamic improvements, including decreased mean pulmonary artery pressure (mPAP) (45±11 mm Hg vs 33±10 mm Hg; p<0.001) and increased cardiac output (4.9±1.6 L/min vs 5.4±1.9 L/min; p=0.011). Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class (3.0±0.5 vs 2.0±0.5; p<0.001) and CPET (13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min; p<0.001). Seventeen patients (85%) were alive after 51±30 months of follow-up.. BPA may offer an alternative form of treatment in selected CTEPH patients. While prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised. Randomised trials are warranted.

Topics: Aged; Angioplasty, Balloon; Arterial Pressure; Biomarkers; Cardiac Catheterization; Cardiac Output; Chronic Disease; Endarterectomy; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism; Recovery of Function; Time Factors; Treatment Outcome; Troponin T; Ventricular Function, Right

Heart failure (HF) is a complex clinical syndrome, resulting from structural and/or functional cardiac disease. The aim of this study was to determine whether the activity of Rho-kinase, which has been identified as an important therapeutic target of cardiovascular disease, is enhanced in HF patients.. Total and phosphorylated forms of myosin binding subunit (t-MBS and p-MBS), a substrate of Rho-kinase, were measured on western blotting in circulating leukocytes, and the p-MBS/t-MBS ratio was defined as an index of systemic Rho-kinase activity. First, during the time-course of acute HF (n=12), Rho-kinase activity was significantly elevated in the acute phase compared to the chronic phase (1.19 ± 0.06 vs. 0.97 ± 0.04, P<0.05). Next, Rho-kinase activity was examined in 30 controls and 130 chronic HF patients (cardiomyopathy, n=57; valvular heart disease, n=35; ischemic heart disease [IHD], n=33; and others, n=5). As compared with the controls, Rho-kinase activity was significantly elevated in the total HF group (1.14 ± 0.02 vs. 0.77 ± 0.05, P<0.0001) and in each underlying heart disease (P<0.05 each). Importantly, in the high-risk non-IHD group, Rho-kinase activity was significantly associated with plasma brain nutriuretic peptide level. Finally, p-MBS was expressed in myocardial biopsy samples (immunohistochemistry) in chronic HF patients (n=36), independent of Rho-kinase activity in leukocytes.. Rho-kinase is activated in HF patients, suggesting that it could be a new therapeutic target of the disorder.  

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Leukocytes; Male; Middle Aged; Natriuretic Peptide, Brain; rho-Associated Kinases

The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored.. We tested in a prospective, placebo-controlled, three-way cross-over, double-blind randomized study the effects of the recombinant form of the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise.. Eleven stable chronic HF patients were randomized to sessions of 6-min treadmill-walking tests during placebo, or levosimendan or R-BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R-BNP effects. BNP blood levels remained unchanged.. The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise.

Topics: Adult; Brazil; Cardiovascular Agents; Chemoreceptor Cells; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Hypercapnia; Hyperventilation; Hypoxia; Infusions, Intravenous; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyridazines; Recombinant Proteins; Respiratory Rate; Simendan; Time Factors; Treatment Outcome

Balneotherapy has been shown to reduce systemic blood pressure in healthy volunteers. Hyperthermia might ameliorate the inflammatory status in heart failure through improving cardiac function. The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF). Thirty-two patients with systolic CHF classified as New York Heart Association functional status II or III were randomized to divide either a balneotherapy group or a control group. The patients in the balneotherapy group were immersed in a hot spring at 40°C for 10 min daily for 2 weeks; the control group patients took a shower daily. The left ventricular ejection fraction (EF) and cardiothoracic ratio (CTR) were evaluated and plasma brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. The clinical symptoms improved after 2 weeks of hot spring therapy. Although the heart rate did not change, clinical symptoms, CTR, EF, and BNP were significantly improved. Moreover, the inflammatory responses, including hsCRP, TNF-α and IL-6 decreased significantly after balneotherapy. The improvement of BNP correlates with the changes in inflammatory biomarkers. Repeated hyperthermia by bathing in a hot spring is therefore considered to improve the cardiac and inflammatory status in patients with CHF.

Topics: Aged; Balneology; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Chronic Disease; Cytokines; Down-Regulation; Female; Heart Failure; Hot Springs; Humans; Hypothermia, Induced; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Japan; Linear Models; Male; Natriuretic Peptide, Brain; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Ventricular Function, Left

To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology.. Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF.. We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n = 307) and all-cause mortality (n = 321), cardiovascular mortality (n = 259) and hospitalization (n = 647) as well as the number of hospitalizations during follow-up for all (n = 1934) and CV causes (n = 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo. Results.  Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion.  Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points.

Topics: Acute-Phase Proteins; Aged; Apolipoprotein A-I; Biomarkers; C-Reactive Protein; Chronic Disease; Female; Fluorobenzenes; Glomerular Filtration Rate; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipocalin-2; Lipocalins; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Norway; Patient Readmission; Peptide Fragments; Predictive Value of Tests; Prognosis; Proto-Oncogene Proteins; Pyrimidines; Rosuvastatin Calcium; Severity of Illness Index; Sulfonamides

Renal handling of sodium and water is abnormal in chronic kidney diseases. To study the function and regulation of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in autosomal dominant polycystic kidney disease (ADPKD), we measured urinary excretion of AQP2 (u-AQP2), the β-subunit of ENaC (u-ENaC(β)), cAMP (u-cAMP), and prostaglandin E(2) (u-PGE(2)); free water clearance (C(H2O)); fractional sodium excretion (FE(Na)); and plasma vasopressin (p-AVP), renin (p-Renin), angiotensin II (p-ANG II), aldosterone (p-Aldo), and atrial and brain natriuretic peptide (p-ANP, p-BNP) in patients with ADPKD and healthy controls during 24-h urine collection and after hypertonic saline infusion during high sodium intake (HS; 300 mmol sodium/day) and low sodium intake (LS; 30 mmol sodium/day). No difference in u-AQP2, u-ENaC(β), u-cAMP, u-PGE(2), C(H2O), and vasoactive hormones was found between patients and controls at baseline, but during HS the patients had higher FE(Na). The saline caused higher increases in FE(Na) in patients than controls during LS, but the changes in u-ENaC(β), p-Aldo, p-ANP, p-BNP, p-Renin, and p-ANG II were similar. Higher increases in u-AQP2 and p-AVP were seen in patients during both diets. In conclusion, u-AQP2 and u-ENaC(β) were comparable in patients with ADPKD and controls at baseline. In ADPKD, the larger increase in u-AQP2 and p-AVP in response to saline could reflect an abnormal water absorption in the distal nephron. During LS, the larger increase in FE(Na) in response to saline could reflect a defective renal sodium retaining capacity in ADPKD, unrelated to changes in u-ENaC(β).

Topics: Adolescent; Adult; Aged; Aldosterone; Angiotensin II; Aquaporin 2; Atrial Natriuretic Factor; Chronic Disease; Cross-Over Studies; Cyclic AMP; Dinoprostone; Epithelial Sodium Channels; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polycystic Kidney, Autosomal Dominant; Renin; Saline Solution, Hypertonic; Sodium; Vasopressins; Young Adult

Diastolic dysfunction (DD) was identified as a predictor of adverse prognosis in heart failure with reduced ejection fraction (HFREF). It is, however, unknown if DD is improved by exercise training, which is known to induce reverse remodelling, and if the training effect is attenuated in elderly HFREF patients. We therefore assessed DD in a cohort of referent controls (RCs) and HFREF patients and studied the response of DD to endurance exercise in two age groups (≤55 years and ≥65 years).. Sixty RC (30 ≤ 55 years, mean age 50 ± 5 years; 30 ≥ 65 years, 72 ± 4 years) and 60 HFREF patients (30 ≤ 55 years, 46 ± 5 years; 30 ≥ 65 years, 72 ± 5 years, EF 28 ± 5%) were randomized to 4 weeks of supervised endurance training or to a control group. Exercise training was effective in reducing LV isovolumetric relaxation time by 29% in young and by 26% in old HFREF patients (P< 0.05 for both). As assessed by tissue Doppler, septal E' increased by 37% in young and by 39% among old HFREF patients (P< 0.005 for both) resulting in a significant decrease in the E/E' ratio from 13 ± 1 to 10 ± 1 in young and 14 ± 1 to 11 ± 1 in old HFREF patients (P< 0.05 for both). Serum levels of N-terminal pro brain natriuretic peptide were significantly reduced after endurance training in HFREF patients of all ages.. In HFREF, diastolic function is significantly impaired in all age groups. Endurance training is highly effective in improving left ventricular diastolic function in HFREF patients regardless of age. This study is registered at ClinicalTrials.gov (number: NCT00176319).

Topics: Age Factors; Aged; Chronic Disease; Electrocardiography; Exercise Test; Exercise Therapy; Exercise Tolerance; Female; Heart Failure, Diastolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left

Loop diuretics have two different classes with different duration of activity: short-acting such as furosemide (duration of activity, 6h) and long-acting such as azosemide (duration of activity, 10-12h). We conducted a multicenter, randomized, controlled trial in order to compare the therapeutic effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting one, on neurohumoral factors and cardiac function in outpatients with chronic heart failure (CHF).. We enrolled 98 patients with CHF who were receiving furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group continued furosemide at the same dosage, and the azosemide group switched from furosemide to azosemide. At baseline and after 3 months, we measured body weight, and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium, and hematocrit. Chest X-ray and echocardiography were also performed.. Body weight and plasma levels of BNP and ANP significantly decreased after 3 months in the azosemide group compared to the furosemide group. There were no significant differences in changes of levels of creatinine, blood urea nitrogen, sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months between the furosemide and azosemide groups. Echocardiography and chest X-ray did not demonstrate significant differences between the two groups.. Long-acting azosemide is suggested to be useful for the improvement of neurohumoral factors compared with short-acting furosemide in patients with CHF.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Delayed-Action Preparations; Echocardiography; Female; Furosemide; Heart Failure; Heart Function Tests; Humans; Male; Natriuretic Peptide, Brain; Outpatients; Sodium Potassium Chloride Symporter Inhibitors; Sulfanilamides

Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT.. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group.. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV.

Topics: Cardiac Resynchronization Therapy; Cheyne-Stokes Respiration; Chronic Disease; Echocardiography; Female; Follow-Up Studies; Heart; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Respiration, Artificial; Treatment Outcome

The aim of this study was to ascertain whether expressions of adipokines in the myocardium or their circulating levels can provide prognostic information concerning patients with chronic heart failure (HF).. Circulating levels of 3 adipokines (leptin, adiponectin, and resistin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein were measured in 96 patients with chronic HF. Major adverse cardiac events (MACE) involving death, heart transplantation, and hospitalization with deteriorating HF during a median follow-up period of 288 days were recorded. From that group, immunohistochemistry and Western blotting studies of the myocardial tissues were conducted on 7 patients with end-stage HF undergoing heart transplantation. The levels of the 3 adipokines significantly correlated with that of NT-proBNP; however, only adiponectin concentration increased with the severity of HF, after correction for body mass index. Cox proportional hazards analyses revealed that high levels of corrected adiponectin were predictive of the development of MACE (hazard ratio, 2.947, P=0.037). Moreover, adiponectin was significantly expressed in the myocardium, and its tissue expression positively correlated with the severity of HF.. This study showed that adiponectin is associated with clinical outcomes and severity of HF. Further research into the precise mechanisms of these adipokine derangements in HF is important to help clarify the exact role of adipokines in the pathophysiology of HF. 

Topics: Adipokines; Adult; Aged; C-Reactive Protein; Chronic Disease; Disease-Free Survival; Female; Gene Expression Regulation; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Survival Rate; Transplantation, Homologous

The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drug's administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

Topics: Aged; Calcium; Chronic Disease; Data Interpretation, Statistical; Diuretics; Drug Administration Schedule; Female; Furosemide; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Hydrazones; Infusions, Intravenous; Male; Mortality; Natriuretic Peptide, Brain; Pyridazines; Severity of Illness Index; Simendan; Treatment Outcome; Ventricular Function

Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown.. One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome.. Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001).. We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Female; Follow-Up Studies; Health Status; Heart Failure, Systolic; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7±9.5 pmol l⁻¹) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P=0.004), while independent predictor of the β-stiffness of carotid artery was the urinary EO (P=0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

Topics: Aged; Antihypertensive Agents; Biomarkers; Blood Pressure Monitoring, Ambulatory; Carotid Artery, Common; Catecholamines; Chronic Disease; Circadian Rhythm; Diabetes Mellitus, Type 2; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Ouabain; Peptide Fragments; Risk Factors

Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program.. 34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that.. In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-γ [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively].. Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

Topics: Acute Disease; Adult; Aged; Biomarkers; Chronic Disease; Coronary Artery Disease; Cytokines; Exercise; Exercise Test; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain

We have reported previously that Waon therapy improves cardiac and vascular function, and prognosis of patients with chronic heart failure (CHF). CHF is characterized by generalized sympathetic activation and parasympathetic withdrawal. The purpose of this study was to evaluate the effect of Waon therapy on autonomic nervous activity in patients with CHF.. Fifty-four patients with CHF, who were receiving conventional therapy for CHF, were divided into Waon therapy and control groups. In the Waon therapy group, 27 patients were treated with medication and Waon therapy. In the control group, 27 patients were treated with only conventional CHF therapy. Cardiac function including cardiac output (CO) and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The heart rate variability, such as the coefficient of variation of RR intervals (CVRR), the low-frequency (LF) component, high-frequency (HF) component, the LF norm [LF/(LF+HF)], and HF norm [HF/(LF+HF)], were measured at admission and 4 weeks after treatment.. Echocardiography demonstrated that CO and LVEF significantly increased after 4 weeks in the Waon therapy group, but did not change in the control group. In the Waon therapy group, CVRR, HF, and HF norm significantly increased 4 weeks after Waon therapy. In addition, the LF/HF ratio and LF norm significantly decreased 4 weeks after Waon therapy. In contrast, these parameters remained unchanged in the control group. Moreover, the HF and HF norm were significantly higher, and the LF/HF ratio and LF norm were significantly lower after 4 weeks of Waon therapy group than after 4 weeks of only conventional therapy.. Waon therapy improved cardiac function and autonomic nervous activity by increasing parasympathetic and decreasing sympathetic nervous activity in patients with CHF.

Topics: Autonomic Nervous System; Cardiac Output; Chronic Disease; Echocardiography; Female; Heart Failure; Humans; Hyperthermia, Induced; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Parasympathetic Nervous System; Radiography, Thoracic; Stroke Volume; Sympathetic Nervous System

To determine whether or not radiofrequency ablation (RFA) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function.. Patients were recruited from heart failure outpatient clinics in Scotland.. Patients with advanced heart failure and severe left ventricular dysfunction were randomised to RFA (rhythm control) or continued medical treatment (rate control). Patients were followed up for a minimum of 6 months.. Change in left ventricular ejection fraction (LVEF) measured by cardiovascular MRI.. 22 patients were randomised to RFA and 19 to medical treatment. In the RFA group, 50% of patients were in sinus rhythm at the end of the study (compared with none in the medical treatment group). The increase in cardiovascular magnetic resonance (CMR) LVEF in the RFA group was 4.5±11.1% compared with 2.8±6.7% in the medical treatment group (p=0.6). The RFA group had a greater increase in radionuclide LVEF (a prespecified secondary end point) than patients in the medical treatment group (+8.2±12.0% vs +1.4±5.9%; p=0.032). RFA did not improve N-terminal pro-B-type natriuretic peptide, 6 min walk distance or quality of life. The rate of serious complications related to RFA was 15%.. RFA resulted in long-term restoration of sinus rhythm in only 50% of patients. RFA did not improve CMR LVEF compared with a strategy of rate control. RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Catheter Ablation; Chronic Disease; Exercise Tolerance; Female; Heart Failure, Systolic; Humans; Magnetic Resonance Angiography; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Radionuclide Ventriculography; Stroke Volume; Ventricular Dysfunction, Left; Young Adult

Multiple B-type natriuretic peptide (BNP) fragments circulate in patients with heart failure (HF) but the types and relative quantities, particularly in relation to bioactive BNP 1-32, remain poorly defined. The purpose of the study was to relate clinically available BNP values with quantitative information on the concentration of pre-secretion and post-processed fragments of BNP detected by mass spectrometry.. Seventy Class I-IV patients were prospectively enrolled with blood drawn into tubes containing a preservative to protect against BNP degradation. Samples were analyzed by quantitative mass spectrometry (MS) immunoassay for intact BNP 1-32 and its fragments. Clinical BNP 1-2 was measured by standard clinical laboratory methods. ProBNP 1-108, corin, and clinically measured BNP levels were elevated, but MS BNP 1-32 levels were low and differed from clinical BNP (P=0.01). Intact MS BNP 1-32 correlated modestly with clinical BNP (r=0.46, P<0.001). MS BNP fragments 3-32, 4-32, and 5-32 demonstrated the best associations with clinical BNP; fragment 5-32 with a correlation coefficient of r=0.81 (P<0.001).. ProBNP 1-108 is measured by clinical BNP assays and contributes to the cumulative results of the BNP assay. However, the observation that clinically measured BNP correlates best with MS degradation fragments and relatively poorly with MS BNP 1-32 suggests that a significant component of circulating clinical BNP is composed of such fragments that are known to demonstrate little biological activity. There appear to be multiple pathways involved in the dysregulation of proBNP in HF, and both the processing of proBNP and the downstream degradation to BNP 1-32 appear to be critical.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Mass Spectrometry; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

To study trends in systemic inflammatory factors and aminoterminal brain natriuretic propeptide (NT-proBNP) in the blood of patients with stage IIA and IIB chronic heart failure (CHF) during therapy aimed at reducing venous congestion.. The study enrolled 52 patients with postinfarction cardiosclerosis (PICS). Clinical, echocardiographic and laboratory studies were conducted. The levels of TNF-alpha, IL-6, IL-10 and C-reactive protein (CRP) were measured by enzyme immunoassay. The concentration of endotoxin (ET) was estimated by the end-point chromogenic LAL test, that of NT-proBNP--by immunochromotographic assay.. In the patients with CHF, clinical signs of pulmonary venous congestion are associated with a statistically significant increase in the blood levels of TNF-alpha and CRP, those of systemic venous congestion are related to a further rise in TNF-alpha levels and elevation of blood concentrations of NT-proBNP, ET and IL-10. Treatment-related reduction in pulmonary venous congection is associated with a decrease in the levels of TNF-alpha, CRP and IL-6; that in systemic venous congestion--with lower concentrations of NT-proBNP, TNF-alpha and ET.. Specific changes in the levels of systemic inflammatory factors and NT-proBNP were found in patients with CHF in the presence of pulmonary and systemic venous congestion. Treatment aimed at elimination of the latter leads to reduction in the levels of systemic inflammatory factors and NT-proBNP.

Topics: C-Reactive Protein; Chronic Disease; Coronary Circulation; Cytokines; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Systemic Inflammatory Response Syndrome; Treatment Outcome; Venous Insufficiency

It remains unclear whether patients with chronic heart failure (CHF) and advanced left ventricular (LV) dysfunction on β-blocker therapy benefit from exercise training (ET).. We studied 45 CHF patients with advanced LV dysfunction [ejection fraction (LVEF) < 25%] and impaired exercise tolerance [normalized peak oxygen uptake (PVO₂) < 70%] receiving a β-blocker: 33 patients participated in a cardiac rehabilitation program with ET (ET group) and 12 did not (inactive control group). Exercise capacity, LV dimension and plasma B-type natriuretic peptide (BNP) were assessed before and after a 3-month study period. At baseline, both groups had markedly reduced LVEF (ET group 18 ± 4% vs. Control group 18 ± 5%, NS) and impaired exercise capacity (normalized PVO₂ 51 ± 10% vs. 55 ± 9%, NS). Although one patient in the ET group withdrew from the program due to worsening CHF, no serious cardiac events occurred during the ET sessions. After 3 months, the ET group (n = 24) had significantly improved PVO₂ by 16 ± 15% (1,005 ± 295 to 1,167 ± 397ml/min, P < 0.001), while the PVO₂ of the control group was unchanged. LV end-diastolic dimension decreased in both groups to a similar extent, but plasma BNP was significantly decreased only in the ET group (432 to 214 pg/ml, P < 0.05).. The data indicate that in CHF patients with advanced LV dysfunction on β-blocker therapy, ET successfully improves exercise capacity and BNP without adversely affecting LV remodeling or causing serious cardiac complications.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Chronic Disease; Diastole; Exercise Therapy; Exercise Tolerance; Female; Heart Failure; Humans; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

To determine whether brain natriuretic peptide (BNP)-guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment.. UPSTEP was an investigator-initiated, randomized, parallel group, multicentre study with a PROBE design. Symptomatic patients with worsening HF, New York Heart Association class II-IV, ejection fraction <40% and elevated BNP levels, were included. All patients (n= 279) were treated according to recommended guidelines and randomized to BNP-guided (BNP) or to conventional (CTR) HF treatment. The goal was to reduce BNP levels to <150 ng/L in younger patients and <300 ng/L in elderly patients, respectively. The primary outcome was a composite of death due to any cause, need for hospitalization and worsening HF. The study groups were well matched, including for BNP concentration at entry (mean: 808 vs. 899 ng/L; P= 0.34). There were no significant differences between the groups regarding either the primary outcome (P = 0.18) or any of the secondary endpoints. There were no differences for the pre-specified analyses; days out of hospital, and younger vs. elderly. A subgroup analysis comparing treatment responders (>30% decrease in baseline BNP value) vs. non-responders found improved survival among responders (P< 0.0001 for the primary outcome), and all of the secondary endpoints were also improved.. Morbidity and mortality were not improved by HF treatment guided by BNP levels. However, BNP responders had a significantly better clinical outcome than non-responders. Future research is needed to elucidate the responsible pathophysiological mechanisms in this sub-population.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Chronic Disease; Disease-Free Survival; Female; Heart Failure; Hospitals; Humans; Male; Natriuretic Peptide, Brain; Norway; Severity of Illness Index; Sweden; Treatment Outcome

This study aimed to clarify the correlation between the myocardial washout rate (WR) of technetium-99m hexakis 2-methoxy-isobutyl-isonitrile ((99m)Tc-sestamibi) and cardiac enzyme levels in patients with acute myocardial infarction (AMI) 6 months after the onset.. Sixty-one consecutive AMI patients (mean age, 66.2 ± 9.7 years) who underwent percutaneous coronary intervention (PCI) on admission were enrolled. Creatinine kinase MB isoenzyme (CK-MB) levels were measured every 3 h. (99m)Tc-sestamibi myocardial scintigraphic images were obtained at the early (30 min) and delayed (4 h) phases after tracer injection for calculating heart-to-mediastinum (H/M) ratios and global WRs at 2 weeks (0 M) and 6 months (6 M) after the onset of AMI. Regional WRs in the culprit lesions (culprit WR) and the extent score (ES) and severity score (SS) of myocardial damage were also calculated.. PCI was performed 8.3 ± 7.7 h after AMI onset. At 6 M, the early H/M ratio (p = 0.04), delayed H/M ratio (p = 0.02), global WR (p = 0.01), culprit WR (p = 0.002), and delayed ES (p = 0.008) were alleviated. At 0 M, the peak CK-MB level correlated with the delayed H/M ratio (p = 0.003), global WR (p = 0.003), culprit WR (p < 0.001), early ES (p = 0.03), delayed ES (p = 0.01), early SS (p = 0.001), and delayed SS (p < 0.001). At 6 M, the peak CK-MB level correlated with the delayed H/M ratio (p < 0.001), global WR (p = 0.005), culprit WR (p = 0.001), early ES (p = 0.001), delayed ES (p < 0.001), early SS (p < 0.001), and delayed SS (p < 0.001).. These results demonstrated that (99m)Tc-sestamibi WR in the chronic phase as well as that in the acute phase reflects the extent of initial myocardial damage in AMI patients after PCI. Moreover, it might indicate the myocardial condition in the clinical course.

Topics: Acute Disease; Aged; Angioplasty; Chronic Disease; Creatine Kinase; Female; Humans; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Time Factors

Patients with chronic kidney disease (CKD) still frequently experience cardiovascular events despite recent progress in treatment. We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events.. Patients with advanced stage CKD (stage III-V with or without peritoneal dialysis) were included in this trial if they were considered at high risk for cardiovascular events [past history of cardiovascular diseases, past history of coronary angiography, presence of endothelial dysfunction measured by reactive hyperemia peripheral arterial tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients were randomly assigned to be treated with or without oral nicorandil, 15 mg/day. BNP values and endothelial function (augmentation index, pulse wave velocity, and reactive hyperemia peripheral arterial tonometry) before and 1 month after the initiation of the trial were assessed.. Nineteen patients (15 men, 4 women) with a mean age of 61 ± 10 (SD) years were included. The median baseline BNP value was 75.3 (interquartile range, 32.1-138.8) pg/ml, and the BNP level was significantly reduced in the nicorandil group (P < 0.05). Regression analysis demonstrated that only the use of nicorandil is related to a decrease of BNP levels [standardized β coefficient, -75.1 (95% CI, -19.7 to -130.6), P = 0.01]. There were no significant changes in the rest of the parameters in the nicorandil group in comparison to the control group. The change in BNP levels was correlated with changes in the augmentation index (P < 0.01) and central pulse pressure (P = 0.03).. Nicorandil treatment may reduce the level of BNP by reducing the central blood pressure in CKD patients.

Topics: Administration, Oral; Aged; Blood Pressure; Cardiovascular Diseases; Chronic Disease; Down-Regulation; Endothelium, Vascular; Female; Humans; Japan; Kidney Diseases; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nicorandil; Peritoneal Dialysis; Prospective Studies; Pulsatile Flow; Regional Blood Flow; Time Factors; Treatment Outcome; Vasodilator Agents

Aim of the study - to determine efficacy of therapy with the use of ivabradine in patients with functional class (FC) III chronic heart failure (CHF) on the basis of assessment of its action on regulatory adaptive status (RAS). We included into the study 100 patients with FC III CHF at the background of ischemic heart disease (IHD) and/or stage III hypertensive disease (HD) receiving complex therapy (quinapril, torasemide, spironolactone). After randomization group 1 comprised 56 patients (age 62.9+/-1.8 years) who were prescribed slow release metoprolol succinate (59.1+/-4.5 mg/day). Group 2 comprised 44 patients (age 59.4+/-1.3 years) who were prescribed If channel inhibitor ivabradine (12.1+/-2.3 mg/day) if beta-blocker use was not possible. Examination at baseline and in 6 months included treadmillometry with assessment of maximal oxygen consumption (VO2 max) at exercise, echocardiography, 24-hour blood pressure monitoring, measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood plasma. For objective qualitative assessment of the state of RAS we used a test of cardio-respiratory synchronism. Therapy with the use of ivabradine improved structural and functional state of the myocardium, elevated tolerance to exercise, caused positive changes of NT-proBNP concentration in blood plasma and VO2 max at exercise. Thus ivabradine probably can serve as alternative to -adrenoblockers when their use is not possible patients with FC III CHF at the background of IHD and/or stage III HD.

Topics: Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Agents; Chronic Disease; Drug Monitoring; Drug Therapy, Combination; Echocardiography; Exercise Tolerance; Female; Heart Failure; Heart Rate; Humans; Hypertension; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Severity of Illness Index; Treatment Outcome

The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management.. It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone.. In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography.. Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes.. In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).

Topics: Aged; Ambulatory Care; Chronic Disease; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Quality of Life; Standard of Care; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left

Exercise oscillatory ventilation (EOV) is a common pattern of breathing in heart failure (HF) patients, and indicates a poor prognosis.. To investigate the effects of adaptive servoventilation (ASV) on ventilatory response during exercise.. We studied 39 HF patients with left ventricular ejection fraction (LVEF) £ 45. Cardiorespiratory polygraphy, cardiopulmonary exercise testing (CPET), echocardiography, and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration were performed. Twenty patients with Cheyne-Stokes respiration and apnoea-hypopnoea index (AHI) ≥ 15/h were identified. Of these, 11 patients were successfully titrated on ASV and continued therapy. In the third month of ASV treatment, polygraphy, CPET, echocardiography, and measurement of NT-proBNP concentration were performed again.. The EOV was detected at baseline in 12 (31%) HF patients, including eight (67%) who underwent ASV. The EOV was associated with significantly lower LVEF, peak oxygen uptake (VO(2)), and ventilatory anaerobic threshold (VAT), and a significantly higher left ventricular diastolic diameter (LVDD), slope of ventilatory equivalent for carbon dioxide (VE/VCO(2)), AHI, central AHI and NT-proBNP concentration. In seven patients with EOV, reversal of EOV in the third month of ASV therapy was observed; only in one patient did EOV persist (p = 0.0156).. The EOV can be reversed with ASV therapy. The EOV in association with central sleep apnoea and Cheyne- -Stokes respiration (CSA/CSR) is prevalent in HF patients and correlates with severity of the disease.

Topics: Adaptation, Physiological; Aged; Breathing Exercises; Cheyne-Stokes Respiration; Chronic Disease; Exercise; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sleep Apnea Syndromes; Ultrasonography

We sought to identify predictors of long-term response to levosimendan therapy among patients' baseline features and treatment-induced changes in acutely decompensated chronic heart failure (ADHF).. Ninety-eight consecutive patients [aged 64+/-10 years, New York Heart Association (NYHA) classes III-IV, left ventricular ejection fraction <35%], 69 treated with levosimendan and 29 with standard therapy, underwent a clinical, echocardiographic and biochemical assessment before and after treatment. All patients were subsequently followed for 6 months for death or rehospitalization for ADHF.. Compared to standard therapy, levosimendan induced a significant improvement in NYHA class (F=37.529, p<0.001), B-type natriuretic peptide (BNP, F=22.917, p<0.001), left ventricular ejection fraction (F=23.561, p<0.001), transmitral E deceleration time (DT, F=6.499, p=0.013) and E/e ratio (F=10.812, p=0.003). During follow-up, 88 of 98 patients (90%) experienced an event. Event-free survival (days alive and out of hospital) at 6 months was similar in two groups (median, 48 days, log-rank test p=0.6760). In the levosimendan group, treatment-induced percent BNP change was the best predictor of events (OR=0.970, 95% CI=0.954-0.986, p<0.001). A cut-off for BNP change of 58% predicted events with 87% sensitivity and 83% specificity. Event-free survival was longer in patients with a BNP reduction > or =58% (median, 135 versus 43 days, p=0.0001).. Treatment-induced BNP reduction is an independent predictor of 6-month outcome following levosimendan therapy in ADHF.

Topics: Acute Disease; Aged; Biomarkers; Cardiotonic Agents; Chronic Disease; Disease-Free Survival; Female; Follow-Up Studies; Heart Failure; Heart Function Tests; Humans; Hydrazones; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Predictive Value of Tests; Pyridazines; Sensitivity and Specificity; Simendan; Ultrasonography

Relative area change (RAC) of the proximal pulmonary artery is a measurement of pulmonary artery distensibility and has been shown to correlate with vasoreactivity studies in patients with idiopathic pulmonary arterial hypertension. We have previously noted a relationship between invasive hemodynamic vasoreactivity testing and long-term response to sildenafil in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We therefore set out to determine whether RAC can provide useful correlatory non-invasive data.. Patients recruited to a randomized, controlled trial (RCT) of sildenafil at 40 mg 3 times daily underwent additional magnetic resonance imaging (MRI) at the baseline of the trial. Eighteen patients had an MRI that led to a diagnosis of inoperable distal CTEPH or significant residual CTEPH post-operatively. The primary end-point was improvement in 6-minute walk test (6MWT) with secondary end-points of right heart catheterization-based hemodynamics, N-terminal pro-brain natriuretic peptide (NT pro-BNP) and functional class. RAC assessed by MRI was correlated with trial end-points.. Fourteen subjects with baseline MRI completed the protocol. RAC was the only baseline variable that correlated at 1 year to the primary end-point of improvement in 6MWT (r = 0.7, p = 0.006), and also to a change in NT pro-BNP (r = 0.59, p = 0.03). Using a cut-off of RAC over 20% there was an 87.5% sensitivity (95% confidence interval [CI]: 45% to 100%) and a 66.7% specificity (95% CI: 22% to 96%) for an improvement in 6MWT of >40 meters.. RAC correlates with functional response to sildenafil, as measured by the 6MWT, and improved heart function, as measured by NT pro-BNP. RAC shows potential in understanding and possibly predicting treatment response.

Topics: Adult; Aged; Cardiac Catheterization; Chronic Disease; Female; Heart; Hemodynamics; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Piperazines; Pulmonary Artery; Purines; Recovery of Function; Sensitivity and Specificity; Sildenafil Citrate; Single-Blind Method; Sulfones; Thromboembolism; Time Factors; Treatment Outcome; Vasodilator Agents; Walking

The purpose of this study was to determine the respiratory, hemodynamic, and clinical effects of switching between beta1-selective and nonselective beta-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD).. Carvedilol, metoprolol succinate, and bisoprolol are established beta-blockers for treating CHF. Whether differences in beta-receptor specificities affect lung or vascular function in CHF patients, particularly those with coexistent COPD, remains incompletely characterized.. A randomized, open label, triple-crossover trial involving 51 subjects receiving optimal therapy for CHF was conducted in 2 Australian teaching hospitals. Subjects received each beta-blocker, dose-matched, for 6 weeks before resuming their original beta-blocker. Echocardiography, N-terminal pro-hormone brain natriuretic peptide, central augmented pressure from pulse waveform analysis, respiratory function testing, 6-min walk distance, and New York Heart Association (NYHA) functional class were assessed at each visit.. Of 51 subjects with a mean age of 66 +/- 12 years, NYHA functional class I (n = 6), II (n = 29), or III (n = 16), and left ventricular ejection fraction mean of 37 +/- 10%, 35 had coexistent COPD. N-terminal pro-hormone brain natriuretic peptide was significantly lower with carvedilol than with metoprolol or bisoprolol (mean: carvedilol 1,001 [95% confidence interval (CI): 633 to 1,367] ng/l; metoprolol 1,371 [95% CI: 778 to 1,964] ng/l; bisoprolol 1,349 [95% CI: 782 to 1,916] ng/l; p < 0.01), and returned to baseline level on resumption of the initial beta-blocker. Central augmented pressure, a measure of pulsatile afterload, was lowest with carvedilol (carvedilol 9.9 [95% CI: 7.7 to 12.2] mm Hg; metoprolol 11.5 [95% CI: 9.3 to 13.8] mm Hg; bisoprolol 12.2 [95% CI: 9.6 to 14.7] mm Hg; p < 0.05). In subjects with COPD, forced expiratory volume in 1 s was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 [95% CI: 1.67 to 2.03] l/s; metoprolol 1.94 [95% CI: 1.73 to 2.14] l/s; bisoprolol 2.0 [95% CI: 1.79 to 2.22] l/s; p < 0.001). The NYHA functional class, 6-min walk distance, and left ventricular ejection fraction did not change. The beta-blocker switches were well tolerated.. Switching between beta1-selective beta-blockers and the nonselective beta-blocker carvedilol is well tolerated but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from beta1-selective beta-blockers to carvedilol causes short-term reduction of central augmented pressure and N-terminal pro-hormone brain natriuretic peptide. (Comparison of Nonselective and Beta1-Selective Beta-Blockers on Respiratory and Arterial Function and Cardiac Chamber Dynamics in Patients With Chronic Stable Congestive Cardiac Failure; Australian New Zealand Clinical Trials Registry, ACTRN12605000504617).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Bisoprolol; Carbazoles; Carvedilol; Chronic Disease; Cross-Over Studies; Echocardiography; Female; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Pulmonary Disease, Chronic Obstructive; Pulse; Respiratory Function Tests; Walking

Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris. We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina.. 65 patients (aged 18-85 years) with angiographically documented coronary artery disease, a positive exercise tolerance test, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. We used computer-generated randomisation to assign patients to allopurinol (600 mg per day) or placebo for 6 weeks before crossover. Our primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain. We did a completed case analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 82040078.. In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s (IQR 211-408) from a baseline of 232 s (182-380), and placebo increased it to 249 s (200-375; p=0.0002). The point estimate (absolute difference between allopurinol and placebo) was 43 s (95% CI 31-58). Allopurinol increased median total exercise time to 393 s (IQR 280-519) from a baseline of 301 s (251-447), and placebo increased it to 307 s (232-430; p=0.0003); the point estimate was 58 s (95% CI 45-77). Allopurinol increased the time to chest pain from a baseline of 234 s (IQR 189-382) to 304 s (222-421), and placebo increased it to 272 s (200-380; p=0.001); the point estimate was 38 s (95% CI 17-55). No adverse effects of treatment were reported.. Allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina.. British Heart Foundation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Angina Pectoris; Blood Pressure; C-Reactive Protein; Cardiovascular Agents; Chronic Disease; Cross-Over Studies; Double-Blind Method; Electrocardiography; Enzyme Inhibitors; Exercise Tolerance; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nitroglycerin; Placebos; Time Factors; Vasodilator Agents; Xanthine Oxidase; Young Adult

We analyzed the inodilator properties of levosimendan in patients with chronic heart failure and severe functional mitral regurgitation.. We studied 20 patients under optimal treatment and in stable clinical condition (New York Heart Association 3.19 + or - 0.66; 70 + or - 7 years). Levosimendan was infused as a bolus (12 microg/kg in 10 min) followed by a 24-h infusion (0.1-0.2 microg/kg per min). Before and after infusion, Doppler echocardiography, brain natriuretic peptide determination and noninvasive hemodynamic monitoring with bioimpedance cardiography were performed.. Levosimendan improved left ventricular ejection fraction (ejection fraction 31 + or - 4 from 27 + or - 4, P < 0.05), decreased brain natriuretic peptide (333 + or - 139 from 629 + or - 63 pg/ml, P < 0.01), reduced mitral valve effective regurgitant orifice area to 27 + or - 5 from 36 + or - 7 mm (P < 0.01) and the velocity of displacement of mitral annulus [ratio between E and E' waves on Doppler and tissue Doppler (E/E') from 22.7 + or - 1.6 to 13.1 + or - 0.6, P < 0.01]. Noninvasive hemodynamic monitoring showed increased acceleration index (a marker of inotropism), and reduced peripheral resistances and thoracic fluid content (P < 0.01). After 4 weeks of washout, some of these effects were still evident.. In patients with chronic heart failure and functional mitral regurgitation, levosimendan acutely improved systolic and diastolic function, reduced mitral regurgitation and modulated neurohormonal activation, with a tendency for these changes to persist over a short-term follow-up.

Topics: Aged; Cardiography, Impedance; Cardiotonic Agents; Chronic Disease; Diastole; Echocardiography, Doppler; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Infusions, Intravenous; Italy; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Pilot Projects; Pyridazines; Severity of Illness Index; Simendan; Stroke Volume; Systole; Time Factors; Treatment Outcome; Vasodilator Agents; Ventricular Function, Left

Exercise training might improve cardiac function as well as functional capacity in patients with chronic heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT pro-BNP), is associated with the severity of the disease, and has been reported to be an independent predictor of outcome in CHF. We evaluated the effect of a four months group-based aerobic interval training program on circulating levels of NT pro-BNP in patients with CHF. We have previously reported improved functional capacity in 80 patients after exercise in this exercise program.. Seventy-eight patients with stable CHF (21% women; 70+/-8 years; left ventricular ejection fraction 30+/-8.6%) on optimal medical treatment were randomized either to interval training (n=39), or to a control group (n=39). Circulating levels of NT pro-BNP, a six minute walk test (6MWT) and cycle ergometer test were evaluated at baseline, post exercise, and further after 12 months.. There were no significant differences in NT pro-BNP levels from baseline to either post exercise or long-term follow-up between or within the groups. Inverse correlations were observed between NT pro-BNP and 6MWT (r=-0.24, p=0.035) and cycle exercise time (r=-0.48, p<0.001) at baseline. But no significant correlations were observed between change in NT pro-BNP and change in functional capacity (6MWT; r=0.12, p=0.33, cycle exercise time; r=0.04, p=0.72).. No significant changes in NT pro-BNP levels were observed after interval training, despite significant improvement of functional capacity.

Topics: Aged; Biomarkers; Chronic Disease; Exercise Therapy; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

To investigate the effects of levosimendan, a positive inotropic agent, on the new heart failure markers immunoglobulin free light chains kappa and lambda (FLC-kappa and FLC-lambda) in decompensated chronic heart failure (HF), 59 patients with New York Heart Association (NYHA) class III-IV HF were enrolled. Patients were randomized into levosimendan (n = 31) and standard HF treatment (n = 29) groups. Serum FLC-kappa and FLC-lambda, brain natriuretic peptide (BNP), and ejection fraction (EF) were measured before treatment and on the 5th day of treatment initiation. Forty-two percent of subjects were females (n = 25) and overall mean age was 64.1 +/- 10.7 years. FLC-kappa (P < 0.05) and FLC-lambda (P < 0.05) were significantly decreased in the levosimendan group compared to baseline, but no difference in either marker in the standard treatment group was observed. Pre- and post-treatment FLC-kappa/FLC-lambda ratios in both groups were similar, whereas FLC-kappa and FLC-lambda levels and the FLC-kappa/FLC-lambda ratio showed no significant correlation with NYHA class, brain natriuretic peptide (BNP) and ejection fraction (EF) levels; and BNP and EF changes after the treatment. Symptomatic improvement in the levosimendan group according to the NYHA class was significantly better than in the standard treatment group (P = 0.044). While 55.2% of patients in the levosimendan group showed a 1-degree shift to lower NYHA classes, 10.3% showed a 2-degree decrease. In conclusion, levosimendan caused short-term hemodynamic and symptomatic improvements, with a more pronounced decrease in FLC levels in patients with advanced decompensated HF.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiotonic Agents; Chronic Disease; Down-Regulation; Female; Heart Failure; Humans; Hydrazones; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Pyridazines; Severity of Illness Index; Simendan; Stroke Volume; Time Factors; Treatment Outcome; Turkey

Sleep-disordered breathing (SDB) is thought to be a state of inflammation caused by hypoxic stress. Whether adaptive servo ventilation (ASV) attenuates the inflammatory response and improves the cardiac function of patients with congestive heart failure (CHF) accompanied by SDB was not been investigated.. Seventeen inpatients with New York Heart Association (NYHA) II or III underwent polysomnography. There was a positive correlation between the apnea hypopnea index and high-sensitivity C-reactive protein (hs-CRP) level (r=0.753, P=0.016). The patients were divided into ASV (n=10) and non-ASV groups (n=7), and CHF-parameters were measured before and after ASV treatment. Improvement was noted for the NYHA class in the ASV group but not in the non-ASV group. In contrast to the non-ASV group, the level of brain natriuretic peptide (BNP), ejection fraction, and hs-CRP levels in the ASV group significantly improved (BNP, 212.1 ± 181.2 to 77.3 ± 54.0 pg/ml [P<0.05]; ejection fraction, 43.5 ± 6.4 to 53.3 ± 6.1% [P=0.002]; hs-CRP, 0.85 ± 0.58 to 0.21 ± 0.19 mg/dl, [P=0.008]). The increase in ejection fraction was correlated with a decrease in the hs-CRP level (r=-0.753, P=0.001).. Anti-inflammatory effects of ASV are important contributors for improving cardiac function in patients with CHF accompanied by SDB. 

Topics: Aged; C-Reactive Protein; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Positive-Pressure Respiration; Sleep Apnea Syndromes; Treatment Outcome

to compare the capabilities of identifying different types of brain natriuretic peptide (BNP) for the evaluation of renal replacement therapy modalities in patients with decompensated chronic heart failure (CHF).. Patients (31 men and 9 women) aged 30 to 82 years with functional class II-IV CHF in its decompensation phase were examined. The patients were divided into 2 groups. A study group received medical therapy for CHF, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, verospirone, beta-adrenoblockers, digoxin, loop diuretics (furosemide, diuver, in the doses not exceeding those taken before admission) in combination with renal replacement therapy: slow continuous ultrafiltration (SCUF) or continuous venovenous hemofiltration (CVVHF). A control group had only medical therapy for CHF (intravenous furosemide in the doses doubling those used before admission, i.e., > or =80 mg/day required for an adequate response to the drug--daily urine volume >1 liter). The patients from the study and control groups received furosemide < or =40 mg/day or torsemide < or =20 mg/day after a course of SCUF or CVVHF sessions or intravenous furosemide. There were 4 examination stages [control study points (CSP)]: (1) before study; (2) after CHF compensation achievement (a day before hospital discharge); (3) following 90 days; (4) following 180 days. The plasma concentration of active BNP was measured by enzyme immunoassay; that of the N-terminal fragment of BNP (NT-proBNP) was estimated on an analyzer.. There were direct correlations between the content of BNP and that of NT-proBNP) in all CSPs in the patients from both groups. The study group showed a significantly greater weight loss, which was accompanied by a more pronounced reduction in systolic pulmonary artery pressure, pulmonary venous hypertension, hydrothorax elimination, decreased liver size, lower plasma aldosterone concentration, decreased heart size, and higher left ventricular ejection fraction (LVEF). The study group displayed a steady-state reduction in the plasma concentrations of both BNP and NT-proBNP, significant inverse correlations between the lower BNP level and the higher LVEF throughout the follow-up.. Extracorporeal dehydration techniques are more effective that intravenous diuretics. The direct correlations between the content of BNP and that of NT-proBNP and between the change in their concentrations during treatment assume the capacity and objectification of diagnosing CHF and its degree, by determining only one of the types of BNP.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Diuretics; Female; Heart Failure; Hemofiltration; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Treatment Outcome; Ultrafiltration

Background Carvedilol may reduce the severity of central sleep apnea (CSA) in patients with chronic heart failure (CHF). Methods and Results This study prospectively examined the effect of carvedilol on the severity of CSA in patients with CHF. Polysomnographic findings, left ventricular (LV) function, and plasma brain natriuretic peptide (BNP) level were evaluated before and 6 months after induction of carvedilol in 16 patients with CHF (New York Heart Association functional class II or III and LV ejection fraction <50%) who had CSA (central apnea index [CAI] >5 with dominant central apneic events). All patients tolerated carvedilol. The 6-month treatment with carvedilol increased the LV ejection fraction (32+/-7.4% to 45+/-9.8%, P<0.001) and decreased the BNP level (159 [69-458] pg/ml to 38 [16-193] pg/ml, P=0.017). The polysomnographic findings showed that the treatment decreased the apnea-hypopnea index (34+/-13 to 14+/-13, P=0.003) and CAI (13+/-11 to 1.9+/-4.3, P<0.001), whereas it increased the obstructive apnea index (1.1+/-1.5 to 3.1+/-3.4, P=0.04). Conclusion This preliminary study shows that treatment with carvedilol reduces the severity of CSA in patients with CHF, but that episodes of obstructive sleep apnea sometimes increase after the treatment.

Topics: Adrenergic beta-Antagonists; Aged; Carbazoles; Carvedilol; Chronic Disease; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Propanolamines; Prospective Studies; Severity of Illness Index; Sleep Apnea, Central; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

This study was designed to compare the specific effects of two heart rates (HR), 55 and 75 b.p.m., in patients with heart failure (HF).. Patients with chronic HF, left ventricular ejection fraction (LVEF) 90% of paced QRS, were included in a randomized cross-over trial of two 3-month periods where pacing rate was set at either 55 or 75 b.p.m. At the end of each period, patients were examined and radionuclide ventriculography, echocardiography, and blood sampling were performed for centralized and blinded analysis. Two patients did not complete the study because of early worsening while paced at 75 b.p.m. Twelve patients completed the study. Compared with 75 b.p.m., pacing at 55 b.p.m. was associated with a higher LVEF [+4.7% (2.6-6.7), P < 0.001], lower B-type natriuretic peptide levels [-91 pg/mL (-148 to -33), P < 0.01], lower systolic pulmonary artery pressure (41 +/- 10 vs. 47 +/- 10 mmHg, P = 0.02) and lower NYHA (New York Heart Association) class (2.2 +/- 0.6 vs. 2.6 +/- 0.5, P = 0.03). The baseline pacing rate prior to inclusion had no effect on results.. HR per se may impact cardiac function and low HR might be beneficial in patients with systolic HF compared with intermediate HR.

Topics: Aged; Cardiac Pacing, Artificial; Chronic Disease; Cross-Over Studies; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Radionuclide Ventriculography; Stroke Volume; Ventricular Function, Left

To test whether canrenone, an aldosterone receptor antagonist, improves left ventricular (LV) remodelling in NYHA class II heart failure (HF). Aldosterone receptor antagonists improve outcome in severe HF, but no information is available in NYHA class II.. AREA IN-CHF is a randomized, double-blind, placebo-controlled study testing canrenone on top of optimal treatment in NYHA class II HF with low ejection fraction (EF) to assess 12-month changes in LV end-diastolic volume (LVEDV). Brain natriuretic peptide (BNP) was also measured. Information was available for 188 subjects on canrenone and 194 on placebo. Left ventricular end-diastolic volume was similarly reduced (-18%) in both arms, but EF increased more (P = 0.04) in the canrenone (from 40% to 45%) than in the placebo arm (from 40-43%). Brain natriuretic peptide (n = 331) decreased more in the canrenone (-37%) than in the placebo arm (-8%; P < 0.0001), paralleling a significant reduction in left atrial dimensions (-4% vs. 0.2%; P = 0.02). The composite endpoint of cardiac death and hospitalization was significantly lower in the canrenone arm (8% vs. 15%; P = 0.02).. Canrenone on top of optimal treatment for HF did not have additional effects on LVEDV, but it increased EF, and reduced left atrial size and circulating BNP, with potential beneficial effects on outcome. A large-scale randomized study should be implemented to confirm benefits on cardiovascular outcomes in patients with HF in NYHA class II.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Canrenone; Chronic Disease; Creatinine; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Treatment Outcome; Ultrasonography; Ventricular Remodeling; Young Adult

Rehabilitation programs involving immersed exercises are more and more frequently used, with severe cardiac patients as well.. This study investigated whether a rehabilitation program including water-based exercises has additional effects on the cardiovascular system compared with a traditional land-based training in heart disease patients.. Twenty-four male stable chronic heart failure patients and 24 male coronary artery disease patients with preserved left ventricular function participated in the study. Patients took part in the rehabilitation program performing cycle endurance exercises on land. They also performed gymnastic exercises either on land (first half of the participants) or in water (second half). Resting plasma concentration of nitric oxide metabolites (nitrate and nitrite) and catecholamine were evaluated, and a symptom-limited exercise test on a cycle ergometer was performed before and after the rehabilitation program.. In the groups performing water-based exercises, the plasma concentration of nitrates was significantly increased (P = 0.035 for chronic heart failure and P = 0.042 for coronary artery disease), whereas it did not significantly change in the groups performing gymnastic exercise on land. No changes in plasma catecholamine concentration occurred.. In every group, the cardiorespiratory capacity of patients was significantly increased after rehabilitation. The water-based exercises seemed to effectively increase the basal level of plasma nitrates. Such changes may be related to an enhancement of endothelial function and may be of importance for the health of the patients.

Topics: Bicycling; Biomarkers; Catecholamines; Chronic Disease; Coronary Artery Disease; Exercise Therapy; Exercise Tolerance; Gymnastics; Heart Failure; Humans; Immersion; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrates; Nitric Oxide; Nitrites; Peptide Fragments; Swimming Pools; Treatment Outcome; Up-Regulation; Ventricular Function, Left

To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure.. Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied.. We analyzed the relationship between baseline NT-proBNP and peak oxygen uptake (peak VO(2)) or distance in the 6-minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak Vo(2) or distance in the 6-minute walk test in the context of other clinical variables. Receiver operator curve analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO(2) <12 mL/kg per minute.. NT-proBNP was the most powerful predictor of peak VO(2) (partial R(2) = 0.13, P < .0001) of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6-minute walk test, this relationship was weaker than that for peak VO(2) (partial R(2) = 0.02, P < .0001). For both peak VO(2) and distance in the 6-minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. Receiver operator curve analysis suggested NT-proBNP had moderate ability to identify patients with peak VO(2) <12 mL/kg per minute (c-index, 0.69).. In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO(2) and a significant predictor of distance in the 6-minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO(2) who might be considered for cardiac transplantation. These data suggest that, although hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables.

Topics: Aged; Biomarkers; Chronic Disease; Cohort Studies; Data Collection; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Prognosis; Protein Precursors; ROC Curve; Ventricular Dysfunction, Left

To compare the effects of lipophilic simvastatin and hydrophilic rosuvastatin on plasma adiponectin and glycated haemoglobin A1c (HbA1c) levels in patients with non-ischaemic chronic heart failure (NICHF).. Seventy-one stable outpatients with NICHF, who were already receiving standard therapy for CHF, were randomized to simvastatin (n = 35) or rosuvastatin (n = 36). Plasma levels of brain natriuretic peptide (BNP), total adiponectin, high-sensitive C-reactive protein, HbA1c, and oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, were measured before and 4 months after treatment with simvastatin or rosuvastatin. There was no difference in the baseline characteristics including left ventricular ejection fraction (LVEF) and biochemical parameters between the two groups. In both groups, plasma BNP levels and LVEF did not change after 4 months. Plasma levels of adiponectin and oxLDL did not change and HbA1c level was slightly increased (6.0 +/- 0.9 vs. 6.1 +/- 0.9%, P = 0.053) in the simvastatin group. In contrast, plasma adiponectin level was significantly increased (12.3 +/- 7.3 vs. 14.0 +/- 8.2 microg/mL, P = 0.012) concomitant with a significant reduction in oxLDL and HbA1c (oxLDL: 8.8 +/- 4.7 vs. 7.6 +/- 4.7 U/mL, P = 0.0059; HbA1c: 6.0 +/- 0.7 vs. 5.9 +/- 0.7%, P = 0.002) in the rosuvastatin group.. These findings suggest that hydrophilic rosuvastatin but not lipophilic simvastatin increases adiponectin and decreases HbA1c levels in patients with NICHF.

Topics: Adiponectin; Aged; C-Reactive Protein; Chronic Disease; Female; Fluorobenzenes; Glycated Hemoglobin; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; Male; Middle Aged; Natriuretic Peptide, Brain; Pyrimidines; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Functional electrical stimulation (FES) improves exercise capacity and endothelial function in chronic heart failure (CHF) patients. This study evaluates the impact of FES on quality of life and emotional stress in patients with moderate to severe CHF.. Thirty patients with stable CHF (24 men; NYHA class II-III; left ventricular ejection fraction <35%) were randomly assigned (2:1) to a 6-week FES training program (n=20) or placebo (n=10). Questionnaires addressing quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall], and emotional stress [Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)], as well as plasma B-type natriuretic peptide (BNP) and 6-min walking distance test (6MWT) were assessed at baseline and after completion of training protocol.. A significant improvement in KCCQ functional (F=76.666, p<0.001), KCCQ overall (F =41.508, p<0.001), BDI (F =17.768, p<0.001) and Zung SDS (F =27.098, p<0.001) was observed in the FES group compared to placebo. Patients in the FES group had also a significant increase in 6MWT (F =19.413, p<0.001) and a trend towards reduction in plasma BNP (F =4.252, p=0.053) compared to placebo.. FES seems to have a beneficial effect on quality of life, exercise capacity and emotional stress in patients with moderate to severe CHF.

Topics: Analysis of Variance; Cardiomyopathy, Dilated; Chronic Disease; Electric Stimulation Therapy; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Placebos; Quality of Life; Statistics, Nonparametric; Stress, Psychological; Surveys and Questionnaires; Treatment Outcome

We compared the effects of telmisartan and olmesartan in 20 patients with chronic heart failure and metabolic syndrome. The subjects underwent once-daily 40 mg telmisartan for at least 3 months before switching to once-daily 20 mg olmesartan for the next 3 months (post 1). They were then treated with 3 months of once-daily 40 mg telmisartan (post 2). Systolic and diastolic blood pressure in the early morning, plasma B-type natriuretic peptide, serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were increased at post 1 (p < 0.005, p < 0.05, p < 0.05, p < 0.05, p < 0.05, and p < 0.005 vs. baseline, respectively) before returning to their baseline values at post 2. The changes in plasma B-type natriuretic peptide levels correlated significantly with the shifts in systolic and diastolic blood pressure in the early morning at posts 1 and 2. Meanwhile, there were no fluctuations in either blood pressure in the late evening or in the outpatient room; nor were there fluctuations in heart rate. Simultaneously, neither serum high-density lipoprotein cholesterol nor fasting blood sugar levels differed significantly between posts. Moreover, telmisartan had more beneficial effects on glucose and lipid profiles in patients with relatively high HbA1c, serum total and low-density lipoprotein cholesterol, and triglyceride levels. Therefore, we concluded that telmisartan was more beneficial than olmesartan for controlling blood pressure in the early morning, as well as for improving glucose and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Glucose; Blood Pressure; Chronic Disease; Female; Glycated Hemoglobin; Heart Failure; Heart Rate; Humans; Hypertension; Imidazoles; Lipid Metabolism; Lipids; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Telmisartan; Tetrazoles

Carperitide is used to treat acute decompensated heart failure (ADHF), but its effects on long-term prognosis have not been studied.. A multicenter randomized controlled study of 49 patients with ADHF was performed to clarify the drug's effects on long-term prognosis. Low-dose carperitide (0.01-0.05 microg x kg(-1 ) x min(-1)) was infused for 72 h as the initial treatment (n=26), whereas in the control group (n=23), standard medical treatment other than carperitide was given without limitation. Anti-aldosterone drugs were prohibited in both groups. During carperitide infusion, significant increases of the atrial natriuretic peptide and cyclic GMP levels and a significant decrease in the heart-type fatty acid-binding protein/serum creatinine ratio were observed, suggesting inhibition of myocyte cell membrane damage. On the other hand, no significant differences in the plasma brain natriuretic peptide, troponin T, and creatinine levels were noted in either group. During 18-month follow-up, significant reductions of death and rehospitalization occurred in the carperitide vs control group (11.5% vs 34.8%; p=0.0359). Cox regression analysis revealed that randomization to carperitide (p=0.020), pretreatment systolic blood pressure >or=140 mmHg (p=0.043), and beta-blocker therapy (p=0.016) were independent predictors for freedom from cardiac events.. Acute-phase low-dose carperitide infusion improved the long-term prognosis of patients with ADHF.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Creatinine; Cyclic GMP; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Remission Induction; Troponin T

We conducted a prospective multicenter case-control study to confirm the clinical efficacy and safety of Waon therapy on chronic heart failure (CHF).. Patients (n=188) with CHF were treated with standard therapy for at least 1 week, and then were randomized to Waon therapy (n=112) or a control group (n=76). All patients continued conventional treatment for an additional 2 weeks. The Waon therapy group was treated daily with a far infrared-ray dry sauna at 60 degrees C for 15 min and then kept on bed rest with a blanket for 30 min for 2 weeks. Chest radiography, echocardiography, and plasma levels of brain natriuretic peptide (BNP) were measured before and 2 weeks after treatment.. NYHA functional class significantly decreased after 2 weeks of treatment in both groups. Chest radiography also showed a significant decrease of the cardiothoracic ratio in both groups (Waon therapy: 57.2+/-8.0% to 55.2+/-8.0%, p<0.0001; control: 57.0+/-7.7% to 56.0+/-7.1%, p<0.05). Echocardiography demonstrated that left ventricular diastolic dimension (LVDd), left atrial dimension (LAD), and ejection fraction (EF) significantly improved in the Waon therapy group (LVDd: 60.6+/-7.6 to 59.1+/-8.4 mm, p<0.0001; LAD: 45.4+/-9.3 mm to 44.1+/-9.4 mm, p<0.05; EF: 31.6+/-10.4% to 34.6+/-10.6%, p<0.0001), but not in the control group (LVDd: 58.4+/-10.3 mm to 57.9+/-10.4 mm; LAD: 46.3+/-9.7 mm to 46.2+/-10.1 mm; EF: 36.6+/-14.1% to 37.3+/-14.0%). The plasma concentration of BNP significantly decreased with Waon therapy, but not in the control group (Waon: 542+/-508 pg/ml to 394+/-410 pg/ml, p<0.001; control: 440+/-377 pg/ml to 358+/-382 pg/ml).. Waon therapy is safe, improves clinical symptoms and cardiac function, and decreases cardiac size in CHF patients. Waon therapy is an innovative and promising therapy for patients with CHF.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chronic Disease; Echocardiography; Female; Heart Failure; Humans; Hyperthermia, Induced; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Radiography, Thoracic

Intravenous levosimendan improves symptoms in acutely decompensated heart failure.. To evaluate the effects of oral levosimendan in severe chronic heart failure (CHF).. 307 patients with NYHA IIIB-IV CHF were randomly assigned, double-blind, to levosimendan 1 mg once or twice daily or placebo for at least 180 days. An exploratory primary end-point, the Patient Journey, a composite consisting of repeated symptom assessments, worsening heart failure and mortality during 60 days was used. Minnesota Living with Heart Failure quality of life score (MLHFQoL) and NT-proBNP were assessed repeatedly.. Patients assigned to a lower dose of levosimendan had more severe CHF at baseline. No differences in symptoms emerged and worsening heart failure events and death were similar resulting in a similar Patient Journey score with levosimendan and placebo (p=0.567). Compared to placebo, a net improvement of 3-4 points in MLHFQoL at several time-points in favour of the combined levosimendan groups was observed (p<0.001) which was accompanied by a substantial and persistent reduction in NT-proBNP (-30-40%) (p<0.001).. Levosimendan improved QoL and decreased NT-proBNP but did not improve the Patient Journey composite in patients with severe CHF. Further research with this compound is warranted to clarify safety and efficacy.

Topics: Aged; Biomarkers; Cardiotonic Agents; Chronic Disease; Disease Progression; Double-Blind Method; Female; Heart Failure; Humans; Hydrazones; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Psychometrics; Pyridazines; Quality of Life; Severity of Illness Index; Simendan; Surveys and Questionnaires

To evaluate the predictive value of admission plasma B-type natriuretic peptide (BNP) and pulmonary capillary wedge pressure (PCWP) for long term cardiovascular events in patients with chronic heart failure (CHF).. A total of 134 patients [70 males and 64 females, mean age (71.28 +/- 8.22) years] with CHF were included in this study. PCWP was measured with a Swan-Ganz catheterization and plasma BNP level was determined by a rapid immunofluorescence assay (Triage, Biosite, USA) in all patients on admission day. Left ventricular end diastolic diameter (LVEDD) and cardiothoracic ratio (CRT) were measured within 24 hours before or after catheterization. All CHF patients received conventional therapy and the rates of cardiac death and rehospitalization were used as end points during 3-year follow up.. (1) LVEDD, CRT, PCWP and BNP were increased in patients with cardiac events compared with patients without cardiac events (P < 0.01). (2) Multivariant logistic analysis showed that PCWP (OR = 1.423, 95% CI 1.163 - 1.741) and BNP (OR = 1.005, 95% CI 1.002 - 1.007) were the independent factors for cardiac events. (3) The area under the receiver operating curve (ROC) of BNP and PCWP to predict cardiac death was 0.846 (95% CI 0.771 - 0.922) and 0.762 (95% CI 0.666 - 0.875), respectively. The sensitivity was 76.5% and the specificity was 75.2% with BNP cutoff point of 720.5 ng/L, and the sensitivity was 68.1% and the specificity was 76.2% with PCWP cutoff point of 19.5 mm Hg (1 mm Hg = 0.133 kPa) for predicting cardiac deaths. (4) The survival rate of patients with BNP < or = 702.5 ng/L and PCWP < or = 19.5 mm Hg were significantly higher than that in patients with BNP > 702.5 ng/L (OR = 4.383, 95% CI 1.407 - 13.650) and PCWP > 19.5 mm Hg (OR = 2.843, 95% CI 1.013 - 8.854).. Both plasma BNP and PCWP on admission day are independent predictors for long term cardiac events in patients with CHF.

Topics: Aged; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Pulmonary Wedge Pressure; ROC Curve; Survival Rate

Endothelial activation and dysfunction may be an important contributor to chronic heart failure (CHF) progression. We sought to investigate whether the calcium sensitizer levosimendan affects beneficially endothelial function and attenuates the deleterious effects of soluble adhesion molecules in patients with advanced CHF.. Twenty-six advanced CHF patients (mean New York Heart Association class, 2.6+/-0.3; ischemic/dilated, 18/8; mean left ventricular ejection fraction <35%) hospitalized due to syndrome worsening, were randomized (2:1) to receive either a 24-h levosimendan infusion of 0.1 microg/kg/min (n=17) or placebo (n=9). Endothelial function estimated by endothelial-dependent flow-mediated dilatation of the brachial artery (FMD), as well as plasma soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), were assessed before and 48 h after therapy.. Baseline characteristics and medications were well balanced in the two treatment groups. A significant improvement of FMD (6.4+/-4.4% from 4.8+/-3.0%; p<0.05) with concomitant reduction of plasma concentrations of sICAM-1 (231+/-75 pg/ml from 339+/-157 pg/ml; p<0.05) and sVCAM-1 (1134+/-508 pg/ml from 1386+/-602 pg/ml; p<0.05) were observed only in levosimendan treated patients.. Levosimendan could be an effective treatment in improving the endothelial function and reducing the detrimental adhesion molecule activation in advanced CHF patients.

Topics: Aged; Chronic Disease; Endothelium, Vascular; Female; Heart Failure; Humans; Hydrazones; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Nitroglycerin; Pyridazines; Severity of Illness Index; Simendan; Solubility; Stroke Volume; Vascular Cell Adhesion Molecule-1; Vasodilation; Vasodilator Agents

Chronic pulmonary arterial thromboembolism (CPATE) often causes right ventricular (RV) pressure overload but the relationship between the degrees of CPATE and RV pressure overload is not clear. To quantify the degrees of CPATE and RV pressure overload, we performed multislice computed tomography (CT) and Tissue Doppler Imaging (TDI) and compared the two modalities.. Sixteen consecutive subjects (4 men, 12 women; age 27-72 with proven CPATE underwent CT. The right vascular obstruction index (VOI), the left VOI, and the total VOI (TVOI) were determined using the scoring system of Qanadli. The early systolic myocardial velocity (Sw) and diastole myocardial velocity (Ew) at the tricuspid annulus and the early diastolic tricuspid inflow (E) were obtained by TDI in the apical four chamber view; RV systolic pressure (RVSP) was estimated by pressure gradient of tricuspid valve regurgitation. E/Ew was calculated as the parameter of RV diastolic function.. The right VOI was 23+/-10%, the left VOI was 18+/-10%, and TVOI was 41+/-14%. The means with ranges of Sw, Ew, E/Ew, RVSP, and brain natriuretic peptide (BNP) were 10.7 (range 7.7-14.6) cm/s, 7.7 (range 4.2-10.6) cm/s, 5.0 (range 2.2-8.1), 55 (range 26-90) mm Hg, and 50.3 (range 12.2-165) pg/ml, respectively. The correlation coefficients between Sw, Ew, E/Ew, RVSP, and BNP and either larger of right or left side (LVOI) and TVOI were 0.041, -0.163 (Sw vs. LVOI, TVOI), -0.153, -0.232 (Ew vs. LVOI, TVOI), 0.145, 0.241 (E/Ew vs. LVOI, TVOI), 0.255, 0.401 (RVSP vs. LVOI, TVOI), and 0.192, 0.170 (BNP vs. LVOI, TVOI), respectively. The correlation coefficient between RVSP and BNP was 0.390.. TVOI was better correlated with RVSP (R=0.401) than the other parameters (Sw, Ew, E/Ew, and BNP), and this was similar to the degree that BNP was correlated with RVSP (R=0.390). TVOI can be a better indicator of RVSP than LVOI. CT VOI may be a useful parameter to assess CPATE morphologically.

Topics: Adult; Aged; Chronic Disease; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism; Tomography, X-Ray Computed; Ventricular Function, Right

The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N-terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure.. Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardiovascular hospitalisation.. NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P < 0.001), BNP 119 to 85 pg/ml (P < 0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P = 0.003), BNP 117 to 93 pg/ml (P = 0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P = 0.06), BNP 114 to 130 pg/ml (P = 0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT-proBNP HR 1.018 95% CI (1.005-1.032), BNP 1.171 (1.088-1.260)).. Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT-proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Enalapril; Europe; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Proportional Hazards Models; Risk Assessment; Time Factors; Treatment Outcome

B-type natriuretic peptide is synthesized in response to increased ventricular wall stress (WS) and hypertrophy. To serially evaluate amino-terminal-pro-BNP (NT-pBNP) serum levels in patients undergoing aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR), blood samples were drawn preoperatively, 15 days postoperatively, at 6- and 12-month follow-up in 25 consecutive patients. Two-dimensional echocardiography was performed concomitantly, assessing left ventricular (LV) dimensional and functional parameters, including WS. Correlations between NT-pBNP, clinical and echocardiographic data were assessed by non-parametric statistics. Median preoperative NT-pro-BNP was 276 pg/ml (IQR=85-1056), being normal or mildly increased in 20 patients, overly increased in five. The most significant correlations of preoperative NT-pBNP were with diastolic (r=0.80, P<0.001) and systolic (r=0.75, P<0.001) meridional WS and inversely with time from symptom onset (r=-0.67, P=0.001). NT-pBNP increased 15 days postoperatively (568 pg/ml, P=0.006 vs. preoperative), then decreased at 6 months (144 pg/ml, P<0.001) to remain stable at 1 year (108 pg/ml, P=0.16). Long-term follow-up NT-pBNP showed direct correlation with diastolic WS (r=0.56, P=0.02). Higher preoperative levels of NT-pBNP predicted greater magnitude of total LV mass regression at follow-up (r=-0.65, P=0.002) independent of preoperative LV mass index, showing that NT-pBNP may have a potential prognostic usefulness in adjunct to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Predictive Value of Tests; Preoperative Care; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Function, Left; Ventricular Remodeling

C-type natriuretic peptide (CNP) is structurally related to cardiac natriuretic peptides and is currently considered as an endothelium-derived hyperpolarizing factor. Endothelial dysfunction, commonly observed in chronic heart failure (HF) patients is positively affected by physical training.. To evaluate the effect of aerobic physical training on the expression of CNP, 90 HF patients on optimal pharmacological treatment (age 62+/-2 years, mean+/-SEM), randomly assigned in a 3 : 1 ratio to either control group (C, 19 patients) or home-based aerobic exercise-training program group (T, 71 patients), completed the protocol. Plasma assay of CNP, brain natriuretic peptide or B-type natriuretic peptide (BNP), and norepinephrine; echocardiogram; and cardiopulmonary-stress test were performed in all patients at enrollment and after 9 months.. At baseline, in both groups, CNP plasma level was significantly related to BNP (R=0.50), ejection fraction (R=0.43), and peak oxygen uptake (VO2, R=0.43, all P<0.001). After 9 months, trained patients showed an improvement in peak VO2 (P<0.001) and ejection fraction (P<0.05), whereas norepinephrine (P<0.05), BNP (P<0.001), and CNP (P<0.001) decreased. No changes occurred in group C. In group T, the decrease in CNP was significantly related to the increase in peak VO2 (R=0.31, P<0.01), and the relation between CNP and BNP was preserved at the end of the program (R=0.41, P<0.001).. Clinical and functional improvement after physical training in HF patients is associated with a decrease in adrenergic activation and in both CNP and BNP concentration. Changes in CNP plasma concentration after physical training might reflect an improvement in endothelial function.

Topics: Biomarkers; Cardiovascular Agents; Chronic Disease; Down-Regulation; Echocardiography; Exercise Test; Exercise Therapy; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Norepinephrine; Oxygen Consumption; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril.. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II the delayed heart/mediastinum count ratio was significantly increased (2.0+/-0.07 vs 2.15+/-0.07, p=0.013) and the washout rate was significantly decreased (33.0+/-1.4 vs 30.5+/-1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased.. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP.

Topics: 3-Iodobenzylguanidine; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Female; Follow-Up Studies; Heart; Heart Failure; Humans; Iodine Radioisotopes; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Perindopril; Radionuclide Imaging; Risk Factors; Stroke Volume; Sympathetic Nervous System; Treatment Outcome

To review the physiological and psychosocial effects of a 12-week T'ai Chi program (TC) in patients with heart failure (HF) as previously reported in a clinical trial.. We randomized 30 patients with chronic HF (left ventricular ejection fraction < or =40%) to receive TC plus usual care (n = 15), or usual care alone (wait-list control, n = 15). Outcome measures included quality of life, exercise capacity, B-type natriuretic peptide, catecholamine levels, heart rate variability, and sleep stability.. The mean age (+/-SD) of patients was 64 +/- 13 years, mean baseline ejection fraction (+/-SD) was 23 +/- 7%, and median New York Heart Association Class was 2 (range 1-4). At 12 weeks, patients who participated in TC showed improved quality of life (mean change -17 +/- 11 vs. 8 +/- 15, Minnesota Living with HF Questionnaire, p = 0.001), increased exercise capacity (mean change 85 +/- 46 vs. -51 +/-58 m, 6-min walk, p = 0.001), and decreased B-type natriuretic peptide (mean change -48 +/- 104 vs. 90 +/- 333 pg/ml, p = 0.03) compared to the control group. Those who participated in TC also showed improvement in sleep stability (increase in high-frequency coupling +0.05 +/- 0.10 vs. -0.06 +/- 0.09 proportion of estimated total sleep time, p = 0.04; reduction in low-frequency coupling -0.09 +/- 0.09 vs. +0.13 +/- 0.13 proportion of estimated total sleep time, p < 0.01), compared to the control group.. TC may enhance quality of life, exercise capacity, and sleep stability in patients with chronic HF.

Topics: Aged; Chronic Disease; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Quality of Life; Sleep Initiation and Maintenance Disorders; Sound Spectrography; Stroke Volume; Tai Ji

Both endurance training (ET) and cardiac resynchronization therapy (CRT) improve quality of life (QOL) and exercise tolerance in patients with advanced chronic heart failure (CHF).. A randomized intervention trial to study the effect on exercise capacity of ET in addition to CRT in patients with CHF and dyssynchrony.. Seventeen patients (eight men, aged 59+/-9 years) with CHF and dyssynchrony were randomized to CRT with (n=8) or without (n=9) ET and compared with two matched control CHF groups (standard care with ET: n=9, standard care only: n=10). At baseline and after 5 months, exercise tolerance, left ventricular (LV) remodelling, QOL and NT-pro brain natriuretic peptide (NT-proBNP) levels were assessed.. Peak oxygen consumption (VO2peak), maximal workload (Wattmax), circulatory power, LV ejection fraction, dyssynchrony and QOL improved in both CRT groups. However, the increase in VO2peak (+40% versus +16%, P=0.005), Wattmax (+43% versus +13%, P=0.0005), and circulatory power (+74% versus +32%, P=0.01), was significantly greater in the trained versus the untrained CRT patients. Comparison of the four patient groups confirmed the cumulative effects of CRT plus ET.. ET in resynchronized CHF patients is feasible and further enhances exercise tolerance. Patients with severe CHF should be prescribed an exercise training programme after implantation in order to maximize the expected benefit.

Topics: Aged; Bundle-Branch Block; Cardiac Output, Low; Cardiac Pacing, Artificial; Chronic Disease; Electric Countershock; Exercise Tolerance; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Physical Endurance; Pilot Projects; Pulmonary Gas Exchange; Quality of Life; Ultrasonography; Ventricular Dysfunction, Left

Chronic thromboembolic pulmonary hypertension (CTEPH) results from non-resolving pulmonary thromboemboli that are resistant to plasmatic anticoagulation. Because of a secondary pulmonary arteriopathy accompanying major vessel obstruction, the disorder may be a target for vasodilator therapy.. In an open-label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH.. Between September 1999 and September 2005, 25 patients were included if their World Health Organization (WHO) functional class was III or IV, if their six-minute walking distance (6-MWD)

Topics: Aged; Antihypertensive Agents; Cardiac Output; Case-Control Studies; Chronic Disease; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Infusion Pumps; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Pain; Pain Measurement; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Risk Assessment; Severity of Illness Index; Thromboembolism; Time Factors; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Walking

Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased in patients with chronic heart failure (CHF). Beta-blockers (BB) may influence these levels but it is unclear whether changes in NT-pro BNP reflect concomitant changes in prognosis.. To assess the prognostic importance of NT-pro BNP at baseline and during follow-up, in patients in whom beta-blocker therapy is initiated.. In COMET, 3029 patients with CHF in NYHA class II-IV and EF<35% were randomised to carvedilol or metoprolol tartrate and were followed for an average of 58 months. Blood samples were collected for the measurement of NT-pro BNP at baseline (n=1559) and during follow-up (n=309).. Baseline plasma concentrations of NT-pro BNP above the median (1242 pg/ml) were associated with higher all-cause mortality (RR 2.77; 95% CI 2.33-3.3, p<0.001). Patients who achieved NT-pro BNP levels<400 pg/ml during follow-up had a lower subsequent mortality (RR 0.32; 95% CI 0.15-0.69, p=0.004).. The plasma concentration of NT-pro BNP is a powerful predictor of mortality in patients with CHF. Patients who achieve an NT-pro BNP of <400 pg/ml subsequent to treatment with a beta-blocker have a favourable prognosis.

Topics: Adrenergic beta-Antagonists; Aged; Carbazoles; Carvedilol; Chronic Disease; Female; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Propanolamines

To evaluate the effects of a comprehensive outpatient rehabilitation program in chronic heart failure (CHF) on quality of life (QoL) in relation to emotional status and clinical severity of disease.. 25 patients with CHF were included in the 12-week comprehensive rehabilitation program. Initially, and at the end of the program, patients underwent graded cardio-pulmonary exercise testing, echocardiography, and determination of brain natriuretic peptide (BNP) concentration. In addition, they were assessed using: The Minnesota Living with Health Failure Questionnaire [MLHFQ]) for disease Specific QoL, the Hospital Anxiety and Depression Scale [HADS], and the State-Trait Anger Expression Inventory [STAXI]).. After 12 weeks of rehabilitation improvements in NYHA class, left ventricular ejection fraction (LVEF), and peak oxygen consumption were found, while mean BNP concentrations did not change. Disease specific QoL demonstrated improvements in physical component and the total score. Relative improvement of psycho-emotional scores correlated positively with relative improvement of disease specific QoL. In patients with LVEF > or =30% at baseline, changes in BNP concentration were positively associated with both anxiety and state anger, and with the emotional component score of MLHFQ.. Improvements in disease-specific QoL were closely associated to improvements of psycho-emotional status and clinical severity of CHF.

Topics: Anxiety; Chronic Disease; Depression; Echocardiography; Emotions; Exercise Test; Female; Heart; Heart Failure; Humans; Immunoassay; Male; Natriuretic Peptide, Brain; Oxygen Consumption; Psychiatric Status Rating Scales; Quality of Life; Severity of Illness Index; Stroke Volume; Surveys and Questionnaires; Treatment Outcome

Suppression of the renin-angiotensin-aldosterone system (RAAS) is therapeutically valuable in chronic heart failure (CHF). RAAS inhibition can be achieved in a number of ways though an orally active renin inhibitor (RI) has never been studied before. We describe the neurohumoral effects of an RI.. 27 patients with NYHA class II or III CHF and an ejection fraction

Topics: Aged; Aldosterone; Amides; Analysis of Variance; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Female; Fumarates; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ramipril; Renin; Statistics, Nonparametric; Treatment Outcome

Patients with chronic heart failure (CHF) have decreased ability to excrete water and increased urinary excretion of aquaporin-2 (U-AQP2). The natriuretic and diuretic effects of furosemide are antagonized by an increased reabsorption of sodium and water in the collecting ducts. It is unknown whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. We tested the hypothesis that U-AQP2 increases after a single intravenous dose of furosemide in CHF patients.. In a randomized, single-blind, placebo-controlled, crossover study, we measured the effect of furosemide (80 mg) on U-AQP2, urine volume, free water clearance (C(H2O)) and fractional excretion of sodium (FE(Na)) in 12 CHF patients. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were measured during the study. U-AQP2 and hormones were determined by radioimmunoassays.. Furosemide increased U-AQP2 (140 %), urine volume (280 %), C(H2O) (95 %) and FE(Na) by a factor of 15 (p<0.008 for all), and also AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did not change.. In CHF, furosemide increased the vasopressin level, which stimulated water reabsorption via the APQ2 water channels. This is most likely a compensatory phenomenon in addition to the increase in the renin-angiotensin system to prevent excess loss of sodium and water. However, both these effects were overridden by the effect of furosemide, as shown by increased free water clearance and sodium excretion.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II; Aquaporin 2; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Cross-Over Studies; Female; Furosemide; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Renin

It was the aim of this study to compare the prognostic impact of echocardiography and brain natriuretic peptide and its N-terminal fragment (NT-proBNP) in patients with chronic heart failure (CHF).. In all, 73 patients with CHF underwent conventional 2-dimensional/Doppler echocardiography and Doppler tissue analysis of systolic, early and late diastolic mitral annular velocities. The mitral filling pattern was classified as restrictive or nonrestrictive. NT-proBNP measurements were carried out on a bench-top analyzer. A cardiac event (rehospitalization caused by worsening CHF, cardiac death, urgent cardiac transplantation) was defined as combined study end point.. During follow-up of 226 +/- 169 days, 27 patients had an event (rehospitalization because of CHF, n = 18; cardiac death, n = 7; urgent transplantation, n = 2). On multivariate Cox regression analysis, a restrictive filling pattern, NT-proBNP, the ratio of peak early diastolic mitral flow to mitral annular E' velocity were independent prognostic predictors. A risk stratification model based on the 3 strongest independent predictors separated groups into those with good, intermediate, and poor outcome (event-free survival of 78%, 46%, and 0%, respectively).. In patients with CHF, Doppler echocardiography, Doppler tissue imaging, and NT-proBNP provide independent and incremental prognostic information. A combined use of echocardiography and NT-proBNP may help to improve risk stratification in this patient population.

Topics: Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Prevalence; Prognosis; Risk Assessment; Risk Factors

A single levosimendan administration has recently been shown to result in clinical and hemodynamic improvement in patients with decompensated heart failure (HF), but without survival benefits. In this study, the effects of levosimendan and dobutamine on plasma levels of proinflammatory and proapoptotic mediators in decompensated HF were compared and correlated with the concomitant effects on cardiac function and prognosis. Sixty-nine patients were randomized to received 24-hour intravenous infusions of levosimendan (n = 23), dobutamine (n = 23), or placebo (n = 23). Echocardiographic, hemodynamic, and biochemical assessments were performed at baseline, immediately after treatment, and 48 hours later. Patients were subsequently followed for 4 months for disease progression. End-systolic wall stress, the left ventricular ejection fraction, pulmonary capillary wedge pressure, and cardiac index were significantly improved in the levosimendan group but remained practically unaffected in the other groups. Plasma N-terminal-pro-B-type natriuretic peptide, tumor necrosis factor-alpha, and soluble Fas ligand levels were significantly decreased only in the levosimendan group (from 1,900 +/- 223 to 1,378 +/- 170 pg/ml, 13.4 +/- 1.0 to 12.3 +/- 1.2 pg/ml, and 68.2 +/- 3.7 to 59.8 +/- 3.6 pg/ml, respectively; p <0.05 for all); interleukin-6 was also borderline reduced (p = 0.051). Levosimendan-induced reduction in end-systolic wall stress was significantly correlated with respective decreases in N-terminal-pro-B-type natriuretic peptide (r = 0.671, p <0.01), tumor necrosis factor-alpha (r = 0.586, p <0.01), soluble Fas (r = 0.441, p <0.05), and soluble Fas ligand (r = 0.614, p <0.01). Event-free survival was significantly longer in the levosimendan group (p <0.05). In conclusion, the superiority of levosimendan over dobutamine in improving central hemodynamics and left ventricular performance in decompensated HF seems to be related to its anti-inflammatory and antiapoptotic effects.

Topics: Aged; Apoptosis; Cardiotonic Agents; Chronic Disease; Dobutamine; Echocardiography; Fas Ligand Protein; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Infusions, Intravenous; Interleukin-6; Male; Membrane Glycoproteins; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Wedge Pressure; Pyridazines; Simendan; Stroke Volume; Treatment Outcome; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors

In patients with chronic heart failure (CHF), N-terminal pro-brain natriuretic peptide (NT-proBNP) provides relevant prognostic information, but its usefulness in the presence of kidney disease has been questioned.. We prospectively enrolled 142 patients with stable CHF and a wide spectrum of renal function (estimated glomerular filtration rates [eGFRs] ranging from 17.1 to 100.3 ml/min/1.73 m2). Chronic kidney disease, defined as eGFR < 60 ml/min/1.73 m2, was present in 63 patients (44%). NT-proBNP measurements were carried out on a bench-top analyzer (Elecsys 2010). Cardiac death or urgent cardiac transplantation were considered as a combined study end-point.. During a follow-up of 383 +/- 237 days, 19 patients underwent a cardiac event (cardiac death, n = 17; urgent cardiac transplantation, n = 2). By multivariate Cox analysis, including clinical and laboratory variables, NT-proBNP and serum hemoglobin were independent prognostic predictors. In patients with NT-proBNP > 1,129 pg/ml, outcome was significantly worse compared to patients with NT-proBNP < 1,129 pg/ml (event-free survival rate 67% vs 94% in those with NT-proBNP < 1,129 pg/ml, p = 0.001). By linear regression analysis, NT-proBNP levels were related to New York Heart Association (NYHA) functional class (R = 0.41, p < 0.001), and inversely related to eGFR (R = -0.29, p = 0.001) and to left ventricular ejection fraction (R = -0.43, p < 0.001).. In CHF patients with and without kidney disease, NT-proBNP provides independent prognostic information. In such patients, NT-proBNP levels are not only reflective of a reduced clearance (i.e., a lower eGFR) but also of the severity of the underlying structural heart disease.

Topics: Adult; Aged; Cardiac Output, Low; Chronic Disease; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Survival Rate

Defective endothelial function has been shown in dilated cardiomyopathy. Therefore, improvement in endothelial function after low-molecular-weight heparin (LMWH) therapy may be clinically beneficial. Consequently, the effect of adjunct enoxaparin, a LMWH, on standard treatment of dilated cardiomyopathy was investigated.. This was a randomized, standard treatment-controlled, 2-center pilot trial of 102 patients (52 receiving adjunctive therapy with enoxaparin at a dosage of 1.5 mg/kg daily for 3 months and 50 receiving standard therapy with angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics alone) with stable chronic heart failure secondary to dilated cardiomyopathy (New York Heart Association [NYHA] class II and III; left ventricular [LV] ejection fraction, < or = 40%). All patients underwent coronary angiography and endomyocardial biopsy and were clinically stable for at least 6 months before enrollment. The combined primary end point included mortality, urgent heart transplantation, and readmission to hospital due to heart failure progression. The secondary end point was to determine the severity of heart failure (serum level of N-terminal brain natriuretic peptide), cardiac function (LV ejection fraction by radionuclide ventriculography), LV diameters by echocardiography, exercise capacity (changes in NYHA class, changes in peak oxygen consumption), and changes in quality of life (Minnesota Living with Heart Failure questionnaire). The clinical outcome was assessed after 6 and 12 months of therapy.. Baseline characteristics were comparable in both groups. Five patients dropped out during 12 months of the study. Twelve patients achieved primary end point (8 in the control group and 4 in the LMWH group). The free survival rate was 94% for the LMWH group and 90% for the controls (not statistically significant). After the 12-month period, in the LMWH group, N-terminal brain natriuretic peptide level and LV diameters decreased significantly (P < .001 and P = .006, respectively), whereas LV systolic function increased (P < .001). Changes in exercise capacity and subjective improvement did not differentiate the groups (nonsignificant). Adverse reactions to the enoxaparin therapy were minor and transient.. In patients with chronic heart failure due to dilated cardiomyopathy, adjunct long-term enoxaparin therapy may offer additional clinical benefit without deleterious effects on major cardiac events.

Topics: Adult; Anticoagulants; Cardiac Output, Low; Cardiomyopathy, Dilated; Cardiovascular Agents; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography; Enoxaparin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Survival Analysis; Systole; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Chronic Disease; Drug Administration Schedule; Drug Resistance; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Injections, Intravenous; Male; Natriuretic Peptide, Brain; Outpatients; Prospective Studies; Time Factors; Treatment Outcome

To study whether the effect of allopurinol on improvement of endothelial dysfunction in chronic heart failure (CHF) translates into improved exercise capacity and to examine whether allopurinol also improves B-type natriuretic peptide (BNP), the other important prognostic marker of CHF.. Randomised, double blind, placebo controlled crossover trial.. Teaching hospital.. 50 patients with CHF (New York Heart Association functional classes II and III) were recruited.. 50 patients with CHF were randomly assigned to three months' treatment with allopurinol (300 mg/day) or placebo. At two and three months into treatment, they underwent a modified Bruce exercise protocol and a six minute walk test. Blood was taken for BNP and haemoglobin analysis.. Neither exercise test was altered by allopurinol. However, plasma BNP concentrations fell significantly (p = 0.035) with allopurinol (11.9 pmol/l) versus placebo (14.4 pmol/l). Haemoglobin concentrations also fell highly significantly with allopurinol (p = 0.001).. An important negative finding is that despite high hopes for it, allopurinol had no effect on exercise capacity in CHF. On the other hand, allopurinol did reduce BNP, which is the best available surrogate marker for prognosis in CHF.

Topics: Aged; Allopurinol; Analysis of Variance; Biomarkers; Chronic Disease; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; Exercise Tolerance; Female; Heart Failure; Hemoglobins; Humans; Male; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Xanthine Oxidase

The aims of this study were to evaluate the effects of beta-blockers on neurohormonal factors in patients with chronic left heart failure (CHF).. 44 patients, 33 men and 11 women, with age of 60.1 +/- 10.6 years with chronic left heart failure (ejection fraction less or equal to 40% by UCG) were included in this study. All patients received conventional therapy and were randomly assigned either to a bisoprolol or carvedilol group. The dosage of beta-blockers were increased gradually to target or the tolerant dosages (bisoprolol 10 mg qd, carvedilol 25 mg bid) during 3 months in 36 patients. Maintenance dose was continued for 4 months. Plasma concentrations of renin activity (PRA), angiotensin II (Ang II), aldosterone (Ald) and the N-terminal portion of brain natriuretic (NT-proBNP) were assessed with RIA and ELISA at baseline and 3 and 7 months after staring beta-blocker therapy. Left ventricular ejection fraction (LVEF, Modify SIMPSON) was assessed at baseline and 7 months after starting therapy.. (1) In patients with left heart failure, the baseline plasma level of PRA, Ang II and Ald were at normal range. N-terminal BNP concentration was much higher than 200 pg/ml as a result of impaired systolic function, as it elevated with increasing of NYHA grade. (2) The plasma level of NT-proBNP decreased significantly, as compared with that before therapy, but there is no significant change of plasma level of PRA, Ang II and Ald. (3) There were no significant differences between the event group and non-event group for the plasma level of renin-angiotensin and aldosterone during 7 months after starting beta-blocker. The Plasma levels of NT-proBNP were much higher in the event group than non-event group. (4) Multi regression analysis showed that the value of LVEF increased with the decreasing of NT-proBNP levels (beta = -0.389, P = 0.009) and increasing of Ang II level (beta = 0.341, P = 0.020) at baseline. After-therapy LVEF increased with the decreasing of NT-proBNP levels at titration-end (beta = -0.424, P = 0.020).. The plasma level of NT-proBNP is more sensitive and accurate than the plasma level of PRA, Ang II and Ald in evaluation of severity and prognosis of CHF. beta-Blocker administration in patients with CHF decreases circulating levels of NT-proBNP and thus improves left ventricular function, but there is no significant effect on plasma level of PRA, Ang II and Ald.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Bisoprolol; Carbazoles; Carvedilol; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Propanolamines; Sensitivity and Specificity; Ventricular Function, Left

Short-term infusion of carperitide (atrial natriuretic peptide) has beneficial effects on neurohumoral factors; however, it remains unclear whether the effects are sustained for long-term infusion. To evaluate the effects of long-term infusion of carperitide on neurohumoral factors in patients with chronic congestive heart failure (CHF), we measured neurohumoral factors before and 1 hour after stopping carperitide infusion in 42 CHF patients. Carperitide infusion was continued for more than 2 days until there was symptomatic improvement of CHF. Patients were divided into 2 groups by the median value of infusion duration: group 1 (less than 7 days, n=21) and group 2 (more than 7 days, n=21). In group 1, aldosterone (ALD) and endothelin-1 (ET-1) were significantly increased after stopping carperitide. In contrast, ALD and ET-1 did not change after stopping carperitide in group 2. The molar ratio of cyclic guanosine monophosphate/atrial natriuretic peptide before stopping carperitide was significantly lower in group 2 than in group 1. Suppression of ALD and ET-1 was maintained for 7 days of carperitide infusion, but the beneficial effect on neurohumoral factors was attenuated after more than 7 days, probably through down-regulation of biologic receptors coupled with guanylate cyclase in CHF patients.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Chronic Disease; Cyclic GMP; Endothelin-1; Female; Heart Failure; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Time Factors; Treatment Outcome

Recently, in a cross-sectional study, a correlation of moderate degree was documented between serum BNP (brain natriuretic peptide) and exercise capacity in patients with chronic heart failure (CHF). However, it remains unknown if BNP, which increases in response to high myocardial wall stress, is sufficiently sensitive for changes in exercise capacity during clinical follow-up. To elucidate this, 42 CHF patients were recruited and randomized into a training (T; 58 +/- 10 years; n = 14 NYHA II; n = 5 NYHA III) and a control group (CO; 54 +/- 9, n = 17 NYHA II; n = 6 NYHA III). T carried out 12 weeks of endurance training on a cycle ergometer (4 sessions per week, 45 min duration). Venous blood sampling and cycle ergometry with simultaneous gas exchange measurements were carried out prior to and after the experimental phase. Due to its superior stability during laboratory procedures, NTproBNP was determined instead of BNP. Both proteins are secreted in equimolar amounts and share an identical diagnostic meaning. In both groups, NT-proBNP decreased slightly (T: from 1092 +/- 980 to 805 +/- 724 pg x ml(-1); CO: from 1075 +/- 1068 to 857 +/- 1138 pg x ml(-1); T vs CO: p = 0.65). Anaerobic threshold (AT) as a measure of exercise capacity went up in T (from 0.96 +/- 0.17 to 1.10 +/- 0.22 l x min(-1)) but remained almost constant in CO (pre: 1.02 +/- 0.27; post: 1.00 +/- 0.27 l x min(-1); T vs CO: p < 0.001). The correlation between changes in NT-proBNP and changes in AT remained insignificant (r = 0.02, p = 0.89)-even if only T was considered (r = 0.09, p = 0.72). Improved exercise capacity in CHF patients due to 3 months of endurance training is not reflected in the course of NT-proBNP. These findings are inconsistent with a sufficient sensitivity of this parameter to detect changes in exercise capacity during clinical follow-up. Changes in NT-proBNP beyond its spontaneous variability are more likely to be detected following therapeutical interventions which aim more clearly at the myocardium. In determining alterations of functional capacity ergometric testing cannot be replaced by serial determinations of NT-proBNP.

Topics: Aged; Anaerobic Threshold; Analysis of Variance; Biomarkers; Cardiomyopathy, Dilated; Chronic Disease; Coronary Disease; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Physical Endurance; Physical Fitness; Predictive Value of Tests; Protein Precursors; Statistics as Topic

Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis.. To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 microg/kg IV bolus followed by an infusion of 0.01 microg/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5+/-0.4 mg/dL and serum creatinine of 1.8+/-0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113+/-51 mL/h with placebo and 110+/-56 mL/h with nesiritide. GFR during placebo was 40.9+/-25.9 mL/min and with nesiritide was 40.9+/-25.8.. Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Creatinine; Cross-Over Studies; Diuresis; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Natriuresis; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Circulation; Treatment Failure; Vasodilator Agents

Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are promising markers for heart failure diagnosis, prognosis, and treatment. Insufficient data on the intraindividual biological variation (CV(i)) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CV(i) values in stable heart failure patients.. We recruited 43 patients with stable chronic heart failure living in Curacao (22 males, 21 females; median age, 63 years; range, 20-86 years; New York Heart Association classes I-III). Samples were collected for within-day CV(i) (n = 6; every 2 h starting at 0800), day-to-day CV(i) (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CV(i) (n = 6; samples collected between 0800 and 1000 on the same day of the week for 6 consecutive weeks). NT-proBNP (Roche) and BNP (Abbott) were measured by immunoassay.. Median (range) concentrations were 134 (0-1630) ng/L (BNP) and 570 (17-5048) ng/L (NT-proBNP). Analytical variation, week-to-week CV(i), and reference change values were 8.4%, 40%, and 113% (BNP), and 3.0%, 35%, and 98% (NT-proBNP). Week-to week CV(i)s were inversely related to median BNP concentrations. Week-to week CV(i)s for BNP were 44% (BNP < or =350 ng/L) and 30% (BNP >350 ng/L). Both BNP and NT-proBNP increased between 0800 and 1000. Median NT-proBNP/BNP ratios were inversely related to median BNP concentrations.. The high CV(i)s hamper interpretation of changes in BNP and NT-proBNP concentrations and may partly explain their poor diagnostic values in chronic heart failure. Easily modifiable determinants to lower CV(i) have not been identified. The value of BNP and NT-proBNP for chronic heart failure diagnosis, and especially for follow-up and treatment optimization of individuals, remains largely to be established.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Time Factors

To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure.. Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or =40% (mean [+/- SD] age, 64 +/- 13 years; mean baseline ejection fraction, 23% +/- 7%; median New York Heart Association class, 2 [range, 1 to 4]) were randomly assigned to receive usual care (n = 15), which included pharmacologic therapy and dietary and exercise counseling, or 12 weeks of tai chi training (n = 15) in addition to usual care. Tai chi training consisted of a 1-hour class held twice weekly. Primary outcomes included quality of life and exercise capacity. Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels. For 3 control patients with missing data items at 12 weeks, previous values were carried forward.. At 12 weeks, patients in the tai chi group showed improved quality-of-life scores (mean between-group difference in change, -25 points, P = 0.001), increased distance walked in 6 minutes (135 meters, P = 0.001), and decreased serum B-type natriuretic peptide levels (-138 pg/mL, P = 0.03) compared with patients in the control group. A trend towards improvement was seen in peak oxygen uptake. No differences were detected in catecholamine levels.. Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving standard medical therapy.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Quality of Life; Surveys and Questionnaires; Tai Ji

This study was designed to evaluate the effects of combined endurance/resistance training on NT-proBNP levels in patients with chronic heart failure (CHF). The safety of resistive weight training for patients with CHF is questioned. Possible detrimental effects include an increase in ventricular diastolic pressure and secondary unfavourable remodelling. Circulating levels of the N-terminal fragment of brain natriuretic peptide (NT-proBNP) reflect left ventricular diastolic wall stress and are strongly related to mortality and treatment success in CHF.. In this study, 27 consecutive patients with stable CHF and left ventricular ejection fraction (LVEF) <35% were enrolled in a 4 months non-randomized combined endurance/resistance training programme. Blood sampling for measurement of NT-proBNP, functional assessment, cardiopulmonary exercise testing, echocardiography and radionuclide angiography were performed at entry and after 4 months. After 4 months, exercise training caused a significant reduction in circulating concentrations of NT-proBNP (2124+/-397 pg/ml before, 1635+/-304 pg/ml after training, p=0.046, interaction), whereas no changes were observed in an untrained heart failure control group. NYHA functional class (p=0.02, interaction), maximal (peak VO2: p=0.035, interaction; maximal workload: p<0.00001, interaction) and submaximal (workload at anaerobic threshold: p=0.001, interaction; rate-pressure product at anaerobic threshold: p=0.001, interaction) exercise parameters as well as work efficiency (Wattmax/VO2peak: p=0.0001, interaction) were significantly improved. In addition, a decrease in left ventricular end-systolic diameter was observed in the trained heart failure group (p=0.016).. Four months of combined endurance/resistance training significantly reduced circulating levels of NT-proBNP in patients with CHF, without evidence of adverse remodelling. Exercise training might offer additional non-pharmacological modulation of the activated neurohormonal pathways in the setting of CHF.

Topics: Bicycling; Chronic Disease; Exercise Test; Exercise Therapy; Exercise Tolerance; Female; Heart Failure; Humans; Jogging; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prospective Studies; Ventricular Remodeling

The prevalence of chronic heart failure (CHF) with systolic dysfunction is increasing. Plasma natriuretic peptides have been envisaged as diagnostic and predictive markers.. To investigate the relationship between the levels of B-type natriuretic peptide (BNP) and A-type natriuretic peptide (ANP) and the clinical and functional parameters of CHF in outpatients with CHF at baseline, compared with normal healthy controls; to find out the differences in a randomised controlled trial between patients treated with an angiotensin-converting enzyme (ACE) inhibitor, captopril, or an angiotensin receptor blocker (ARB), irbesartan. These differences were assessed throughout the six-month treatment period and at the sixth month.. Plasma BNP (pmol/L) and ANP (pmol/L) were determined in 68 hypertensive patients with dilated cardiomyopathy, NYHA class III-IV and ejection fraction (EF) < or = 40%, and in 26 normal controls. Statistical analysis for BNP and ANP was done by Students t-test. The patient group was randomly subdivided into two subgroups of 34 patients, each treated with either an ARB, irbesartan, or an ACE inhibitor (ACE-I), captopril. BNP and ANP were measured in both subsamples and correlated with clinical, functional and neurohormonal parameters throughout a follow-up period of six months and at the sixth month.. The mean EF in the patient sample was 33.43+/-6.52% and in the controls was 61.96 +/-3.53% (p=0.000). The mean BNP (pmol/L) in patients was 44.78+/-54.36 and in the controls was 7.12+/-8.28 (p=0.000) and the mean ANP (pmol/L) was 30.32+/-25.97 in patients and 11.18+/-7.92 in controls (p=0.000). A statistically significant difference was found between patients and healthy controls. Significant correlations were found between natriuretic peptides and EF. Between the baseline phase and the sixth month, BNP and ANP decreased significantly in the ARB group. At the sixth month, both BNP and ANP were lower in the ARB group. Evidence of clinical benefit was found with both ARB or ACE-I treatment throughout the six months, with patients moving from classes III and IV to class II NYHA. Improvement of EF was also found, with transition of patients with lower EF (even <30%) to higher values. EF was higher in the ARB group at the sixth month.. BNP and ANP can be useful diagnostic tools in hypertensive CHF patients with moderate-to-severe LV dysfunction. The decrease in BNP and ANP in the ARB group throughout six months, as well as the lower value at the sixth month, suggest a prognostic value of these parameters.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Biphenyl Compounds; Captopril; Cardiac Output, Low; Chronic Disease; Echocardiography; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Humans; Irbesartan; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Radiography, Thoracic; Radionuclide Ventriculography; Tetrazoles; Ventricular Dysfunction, Left

Several evidence-based treatment regimens are modestly effective in patients with moderately severe to severe heart failure, but truly effective therapies that improve symptoms, reduce hospitalizations, and extend meaningful survival do not exist for these patients. Only ventricular replacement therapy, with either heart transplantation or left ventricular assist devices, has been shown to significantly improve outcomes. Nesiritide, a recombinant B-type natriuretic peptide, is associated with significant reductions in filling pressure, with corresponding relief of symptoms, and diminished neurohormonal levels and has no inotropic effects and no evidence of proarrhythmia when given to patients with decompensated acute heart failure. Results of the Follow-Up Serial Infusion of Nesiritide (FUSION) trial suggest that a regimen incorporating nesiritide can be accomplished with a reasonable assurance of safety and tolerability; pre-study concerns regarding hypotension were not realized. A qualified look at outcomes data within FUSION I suggests that further study of this paradigm is reasonable, especially if the studied patient population includes patients with a low left ventricular ejection fraction and New York Heart Association (NYHA) class III disease with renal insufficiency, or patients with low left ventricular ejection fraction and NYHA class IV heart failure. Therefore, FUSION II, a double-blind, placebo-controlled trial, will randomly assign approximately 900 such patients to treatment with usual care plus nesiritide or usual care plus placebo and will use mortality/cardiorenal hospitalization as a composite end point. If positive data emerge from FUSION II that either confirm or strengthen the data in FUSION I, a new therapeutic option may be available for patients with chronic decompensated heart failure.

Topics: Aged; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Heart Failure; Humans; Infusions, Intravenous; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Severity of Illness Index; Treatment Outcome

C-type natriuretic peptide (CNP) is a vasodilator produced by the vascular endothelium. It shares structural and physiological properties with the cardiac hormones atrial natriuretic peptide and brain natriuretic peptide (BNP), but little is known about its pathophysiological role in chronic heart failure (CHF). We assessed the hypothesis that CNP is produced by the heart in patients with CHF.. Myocardial CNP production was determined (difference in plasma levels between the aortic root and coronary sinus [CS]) in 9 patients undergoing right and left heart catheterization as part of their CHF assessment (all male, age 59+/-9 years; New York Heart Association class 2.2+/-0.1; left ventricular ejection fraction 29+/-5%; creatinine 105+/-8 micro mol/L [all values mean+/-SEM]). BNP, established as originating from myocardium, was assessed from the same samples as a positive control. Analyses were performed by a blinded operator using a standard competitive radioimmunoassay kit (Peninsula Laboratories, Bachem Ltd UK). A step-up (29%) in plasma CNP concentration was found from the aorta to the CS (3.55+/-1.53 versus 4.59+/-1.54 pg/mL, respectively; P=0.035). The mean increase in CNP was 0.90+/-0.35 pg/mL (range 0.05 to 2.80 pg/mL). BNP levels increased by 57% from aorta to CS (86.0+/-20.5 versus 135.0+/-42.2 pg/mL; P=0.01). CS CNP levels correlated with mean pulmonary capillary wedge pressure (r=0.82, P=0.007).. We have shown that CNP is produced by the heart in patients with CHF. Although further evaluation is required to define its full pathophysiological role in this condition, CNP may represent an important new local mediator in the heart.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Chronic Disease; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Dysfunction, Left

To determine whether the plasma concentration of the putative new cardiac hormone relaxin is predictive of clinical outcome in patients with chronic heart failure (CHF).. Plasma relaxin and N-terminal pro B type natriuretic peptide (NT pro BNP) concentrations were measured in 87 patients admitted in an emergency with CHF caused by left ventricular systolic dysfunction. These were related to death and death or readmission with CHF over the following year.. Western Infirmary, Glasgow, UK.. Plasma concentrations of relaxin and NT pro BNP; time to death or hospitalisation caused by heart failure.. Plasma concentrations of both relaxin and NT pro BNP were greatly increased. Of the 43 patients with NT pro BNP above the group median concentration, 23 (53%) died and 30 (70%) died or were hospitalised with CHF. Among the 44 with concentrations below the median, these numbers were 5 (11%) and 12 (27%), respectively (p < 0.0001 and p < 0.0001, respectively). Plasma NT pro BNP concentration remained an independent predictor of an adverse clinical outcome in a multivariate analysis. Of the 42 patients with a relaxin concentration above the median, 13 (31%) died and 20 (48%) died or were hospitalised. Below the median, these numbers were 15 of 45 (33%) and 22 of 45 (49%) (p = 0.76 and p = 0.84, respectively).. NT pro BNP is a powerful and independent predictor of outcome in CHF, whereas relaxin, also secreted by the heart in increased amounts in CHF, is not.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Relaxin; Survival Analysis

Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol.. Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip -3.5 U for carvedilol versus -1.2 U for metoprolol and -2.2 U for placebo, P=0.15; cold pressor test 3.1+/-8.9 U for carvedilol versus 9.0+/-2.7 U for metoprolol and 8.2+/-5.8 U for placebo, P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups.. Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by alpha-adrenergic blockade.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Carbazoles; Carvedilol; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Exercise; Female; Forearm; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Norepinephrine; Propanolamines; Prospective Studies; Reference Values; Regional Blood Flow; Vascular Resistance; Vasodilator Agents; Vasomotor System

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

Topics: 3-Iodobenzylguanidine; Angina Pectoris; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Female; Follow-Up Studies; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic

Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and perhaps endothelin-1 in patients with congestive heart failure. Patients (n = 107) with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction <40%, and on ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C-terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p = 0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not change, and brain natriuretic peptide (BNP) levels tended to decrease similarly in both groups. Endothelin-1 levels increased in both groups, the increase reaching statistical significance with omapatrilat (p = 0.008). Levels of the proinflammatory cytokine interleukin-6 tended to decrease, and the anti-inflammatory cytokine interleukin-10 increased in both groups, with statistical significance only for interleukin-10 with omapatrilat therapy. Neither agent changed catecholamines or angiotensin II. Thus, even at trough levels, omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified, providing potential explanations for differences in clinical outcome.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cytokines; Double-Blind Method; Endothelin-1; Female; Follow-Up Studies; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Predictive Value of Tests; Prospective Studies; Pyridines; Stroke Volume; Thiazepines; Treatment Outcome

Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known.. Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or beta-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (+/-SEM) BNP increased from baseline by 23+/-5 pg/mL in the placebo group (n=1979) but decreased by 21+/-5 pg/mL (n=1940) in the valsartan group (P<0.0001). NE increased by 41+/-6 pg/mL (n=1979) and 12+/-6 pg/mL (n=1941) for placebo and valsartan, respectively (P=0.0003). Concomitant therapy with both ACE inhibitors and beta-blockers significantly reduced the effect of valsartan on BNP but not on NE (P for interaction=0.0223 and 0.2289, respectively).. In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Chronic Disease; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Survival Rate; Tetrazoles; Time; Valine; Valsartan

Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function.. We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286 +/- 31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33 +/- 3 pg/mL. Patients with restrictive like filling patterns on echocardiography had the highest BNP levels (408 +/- 66 pg/mL), and patients with symptoms had higher BNP levels in all diastolic filling patterns. The area under the receiver-operating characteristic curve for BNP to detect any diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95; P<0.001). A BNP value of 62 pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for detecting diastolic dysfunction.. A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography. In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction.

Topics: Aged; Area Under Curve; Atrial Function, Left; Atrial Natriuretic Factor; Chronic Disease; Diastole; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Ventricles; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Assessment of left atrial appendage (LAA) function with transesophageal echocardiography is useful for detecting patients at high risk for thromboembolism as a result of atrial fibrillation (AF). A recent study reported that the atrium is the main source of brain natriuretic polypeptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess a possible relationship between LAA function and plasma BNP levels in nonvalvular AF.. Thirty-four consecutive patients with chronic nonvalvular AF (age, 69+/-9 years) underwent transesophageal echocardiography and plasma BNP measurement. Thirteen patients with a history of thromboembolism or echocardiographic evidence of thrombus (E + group) were compared with 21 AF patients without complications (E- group).. The E+ group patients demonstrated greater impairment of LAA velocity and higher plasma BNP levels than the E- group patients (LAA velocity: 12+/-6 versus 31+/-17 cm/s, P<0.05; plasma BNP: 126+/-53 versus 86+/-45 ng/L, P<0.05). Overall analysis of the continuous variables with multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a weak but significant negative correlation between plasma BNP levels and LAA flow velocity (r=0.38, P<0.05). No intergroup difference in plasma atrial natriuretic polypeptide levels was found.. The present data suggest the usefulness of measuring plasma BNP levels, which may reflect augmented atrial secretion of BNP from the impaired atrial myocardium, in detecting patients at high risk for thromboembolic complications in nonvalvular AF.

Topics: Adult; Aged; Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Biomarkers; Blood Flow Velocity; Chronic Disease; Echocardiography, Transesophageal; Electrocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Thromboembolism

Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure.. Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS).. The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Brachial Artery; Chronic Disease; Drug Therapy, Combination; Endothelium, Vascular; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Lipid Peroxidation; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Stroke Volume; Tetrazoles; Time Factors; Treatment Outcome

We sought to assess plasma concentrations of the amino (N)-terminal portion of pro-brain natriuretic peptide (N-BNP) and adrenomedullin for prediction of adverse outcomes and responses to treatment in 297 patients with ischemic left ventricular (LV) dysfunction who were randomly assigned to receive carvedilol or placebo.. Although neurohormonal status has known prognostic significance in heart failure, the predictive power of either N-BNP or adrenomedullin in chronic ischemic LV dysfunction has not been previously reported.. Plasma N-BNP and adrenomedullin were measured in 297 patients with chronic ischemic (LV) dysfunction before randomization to carvedilol or placebo, added to established treatment with a converting enzyme inhibitor and loop diuretic (with or without digoxin). The patients' clinical outcomes, induding mortality and heart failure events, were recorded for 18 months.. Above-median N-BNP and adrenomedullin levels conferred increased risks (all p < 0.001) of mortality (risk ratios [95% confidence intervals]: 4.67 [2-10.9] and 3.92 [1.76-8.7], respectively) and hospital admission with heart failure (4.7 [2.2-10.3] and 2.4 [1.3-4.5], respectively). Both of these predicted death or heart failure independent of age, New York Heart Association functional class, LV ejection fraction, previous myocardial infarction or previous admission with heart failure. Carvedilol reduced the risk of death or heart failure in patients with above-median levels of N-BNP or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value.. In patients with established ischemic LV dysfunction, plasma N-BNP and adrenomedullin are independent predictors of mortality and heart failure. Carvedilol reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and adrenomedullin.

Topics: Adrenergic beta-Antagonists; Adrenomedullin; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Peptides; Prognosis; Propanolamines; Risk Factors; Ventricular Dysfunction, Left

The study tested the hypothesis that left atrial appendage (LAA) dysfunction in nonvalvular atrial fibrillation (NVAF) correlates with a prothrombotic state, and investigated whether the plasma natriuretic peptides are marker of LAA dysfunction in NVAF. Sixty-seven patients underwent transthoracic and transesophageal echocardiography. The left ventricular fractional shortening, left atrial diameter (LAD), LAA flow velocity and the grade of spontaneous echo contrast (SEC) were determined. The plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), D-dimer, and thrombin-antithrombin III complex (TAT) were measured. The patients were divided into 2 groups according to LAA flow velocity: group I (LAA velocity <20 cm/s) and group II (LAA velocity > or = 20cm/s). The SEC score, D-dimer, TAT, BNP and LAD were significantly increased in group I. Based on simple linear regression analysis, SEC score (r=-0.638), LAD (r=-0.493), D-dimer (r = -0.485), BNP (r = -0.463), TAT (r = -0.455) and age (r = -0.314) were inversely correlated with LAA flow velocity. Multivariate analysis showed that SEC score (p = 0.0014) and plasma BNP level (p=0.0075) were independent negative predictors for LAA flow velocity. In conclusion, LAA dysfunction is associated with a prothrombotic state, and the plasma BNP concentration may serve as a determinant of LAA function in NVAF.

Topics: Aged; Atrial Appendage; Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Biomarkers; Blood Flow Velocity; Chronic Disease; Echocardiography, Transesophageal; Humans; Middle Aged; Natriuretic Peptide, Brain; Thrombophilia

The efficacy of treating dilated cardiomyopathy with metoprolol was compared with that of carvedilol. Metoprolol was administered to 29 patients, and carvedilol to 62. Patients who could not be dosed with up to 40 mg daily of metoprolol or 20 mg daily of carvedilol were defined as intolerant. As well as the tolerability of these beta-blockers, the effects on left ventricular end-diastolic dimension (LVDd), fractional shortening (FS), plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations, the delayed heart and mediastinum (H/M) ratio determined from metaiodobenzylguanidine imaging were compared. Drug intolerance occurred in 24% of patients in the metoprolol group and 19% in the carvedilol group. Among the drug-tolerant patients, LVDd, FS and plasma BNP concentration improved in both groups and to the same degree. Only 25% of drug-tolerant patients in the metoprolol group had a delayed H/M ratio below 1.9 compared with 57% in the carvedilol group. Both metoprolol and carvedilol, when tolerated, improve cardiac function and neurohumoral factors to the same degree. However, carvedilol is preferable to metoprolol for patients with a low delayed H/M ratio.

Topics: 3-Iodobenzylguanidine; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Carbazoles; Cardiomyopathy, Dilated; Carvedilol; Chronic Disease; Female; Hemodynamics; Humans; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Propanolamines; Therapeutic Equivalency; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Most patients with chronic heart failure (CHF) receive the same dose of angiotensin-converting enzyme (ACE) inhibitors because there is currently no measure of treatment efficacy. We sought to determine whether titration of vasodilator therapy according to plasma brain natriuretic peptide (BNP) concentration may be of value in the individual optimization of vasodilator therapy in CHF.. Twenty patients with mild to moderate CHF receiving stable conventional therapy including an ACE inhibitor were randomly assigned to titration of ACE inhibitor dosage according to serial measurement of plasma BNP concentration (BNP group) or optimal empirical ACE inhibitor therapy (clinical group) for 8 weeks. Only the BNP-driven approach was associated with significant reductions in plasma BNP concentration throughout the duration of the study and a significantly greater suppression when compared with empiric therapy after 4 weeks [-42.1% (-58.2, -19.7) vs -12.0% (-31.8, 13.8), P =.03]. Both treatment strategies were well tolerated and associated with favorable neurohormonal and hemodynamic effects; however, in comparison between groups, mean heart rate fell (P =.02) and plasma renin activity rose (P =.03) in the BNP group when compared with the clinical group.. Plasma BNP concentration may be chronically reduced by tailored vasodilator therapy in CHF. Furthermore, titration of vasodilator therapy according to plasma BNP was associated with more profound inhibition of the renin-angiotensin-aldosterone system and significant fall in heart rate when compared with empiric therapy.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renin-Angiotensin System; Single-Blind Method; Titrimetry; Vasodilator Agents

B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are secreted from the heart and are thought to be equally important factors in the regulation of vascular tone in health and in congestive heart failure (CHF). However, no studies directly compare vasodilator effects of these peptides in healthy subjects and in patients with CHF.. Plethysmography was used to determine the vasodilatory effects of BNP and to compare these to the effects of ANP in patients with CHF (n = 15) and age-matched healthy subjects (n = 16). Graded doses of ANP and BNP (8, 16, 32, and 48 pmol/min per 100 ml of tissue volume for both) were administered randomly into the brachial artery. Forearm blood flow (FBF) was measured, and cyclic GMP (cGMP) spillover was calculated.. Responses in FBF to both peptides in CHF were significantly lower than those of healthy subjects (BNP p < 0.05; ANP p < 0.01). Similarly, forearm spillover of cGMP was significantly lower in CHF than in healthy subjects (BNP p < 0.05; ANP p < 0.01). When vascular responses in healthy subjects were compared between BNP and ANP, BNP-induced changes in FBF (p < 0.05) and forearm cGMP spillover (p < 0.01) were significantly less than changes induced by ANP. In CHF, though, FBF change and cGMP spillover induced by the two peptides were not significantly different.. These results suggest that the metabolism and action of these natriuretic peptides in CHF may differ from the healthy state.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Female; Forearm; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Plethysmography; Regional Blood Flow; Vasodilation

The relief of congestion is crucial to improve heart failure (HF) patient's quality of life and prognosis. N-terminal-pro-brain natriuretic peptide (NT-proBNP) is a well-known marker of congestion, although with limited specificity. Peak atrial longitudinal strain (PALS) by speckle tracking echocardiography (STE) is an index of intracardiac pressure and HF prognosis. We aimed to determine the association between NT-proBNP and PALS and its prognostic implications in patients with HF.. Patients hospitalized for de-novo or recurrent HF and outpatients with chronic HF were included in this retrospective study. Patients with missing data, previous cardiac surgery, non-feasible STE were excluded. Clinical, laboratory and echocardiographic data were collected. STE was performed on echocardiographic records. Primary endpoint was a combination of all-cause death and HF hospitalization.. Overall, 388 patients were included (172 acute HF, 216 chronic HF, mean age = 65 ± 12 years, 37% female). Mean LV ejection fraction = 31 ± 9%. Global PALS showed a significant inverse correlation with NT-proBNP in acute and chronic HF (all p < 0.001). During a median follow-up of 4 years, 180 patients reached the combined endpoint. NT-proBNP (AUC = 0.87) and global PALS (AUC = 0.82) were good predictors of the combined endpoint. Global PALS was the only independent predictor of the combined endpoint. Optimal risk stratification for the composite endpoint was provided combining PALS ≤15% and NTproBNP ≥874.5 ng/l.. Global PALS is associated with NT-proBNP in acute and chronic HF and may be used as additional index of congestion to optimize therapeutic management. The combination of global PALS and NT-proBNP could enhance the prognostic stratification of HF.

Topics: Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Quality of Life; Retrospective Studies; Stroke Volume

Natriuretic peptide (NP) testing is recommended for patients presenting to primary care with symptoms of chronic heart failure (HF) to prioritise referral for diagnosis.. To report NP test performance at European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guideline referral thresholds.. Diagnostic accuracy study using linked primary and secondary care data (2004 to 2018).. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NP testing for HF diagnosis was assessed.. In total, 229 580 patients had an NP test and 21 102 (9.2%) were diagnosed with HF within 6 months. The ESC NT-proBNP threshold ≥125 pg/mL had a sensitivity of 94.6% (95% confidence interval [CI] = 94.2 to 95.0) and specificity of 50.0% (95% CI = 49.7 to 50.3), compared with sensitivity of 81.7% (95% CI = 81.0 to 82.3) and specificity of 80.3% (95% CI = 80.0 to 80.5) for the NICE NT-proBNP ≥400 pg/mL threshold. PPVs for an NT-proBNP test were 16.4% (95% CI = 16.1 to 16.6) and 30.0% (95% CI = 29.6 to 30.5) for ESC and NICE thresholds, respectively. For both guidelines, nearly all patients with an NT-proBNP level below the threshold did not have HF (NPV: ESC 98.9%, 95% CI = 98.8 to 99.0 and NICE 97.7%, 95% CI = 97.6 to 97.8).. At the higher NICE chronic HF guideline NP thresholds, one in five cases are initially missed in primary care but the lower ESC thresholds require more diagnostic assessments. NP is a reliable 'rule-out' test at both cut-points. The optimal NP threshold will depend on the priorities and capacity of the healthcare system.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Referral and Consultation; Secondary Care

Current approaches to classify chronic heart failure (HF) subpopulations may be limited due to the diversity of pathophysiology and co-morbidities in chronic HF. We aimed to elucidate the clusters of chronic patients with HF by data-driven approaches with machine learning in a hospital-based registry.. A total of 4649 patients with a broad spectrum of left ventricular ejection fraction (LVEF) in the CHART-2 (Chronic Heart Failure Analysis and Registry in the Tohoku District-2) study were enrolled to this study. Chronic HF patients were classified using random forest clustering with 56 multiscale clinical parameters. We assessed the influence of the clusters on cardiovascular death, non-cardiovascular death, all-cause death, and free from hospitalization by HF. Latent class analysis using random forest clustering identified 10 clusters with four primary components: cardiac function (LVEF, left atrial and ventricular diameters, diastolic blood pressure, and brain natriuretic peptide), renal function (glomerular filtration rate and blood urea nitrogen), anaemia (red blood cell, haematocrit, haemoglobin, and platelet count), and nutrition (albumin and body mass index). All 11 significant clinical parameters in the four primary components and two disease aetiologies (ischaemic heart disease and valvular heart disease) showed statistically significant differences among the 10 clusters (P < 0.01). Cluster 1 (26.7% of patients), which is characterized by preserved LVEF (<59%, 37% of the total) with lowest brain natriuretic peptide (>111.3 pg/mL, 0.9%) and lowest left atrial diameter (>42 mm, 37.4%), showed the best 5 year survival rate of 98.1% for cardiovascular death, 95.9% for non-cardiovascular death, 92.9% for all-cause death, and 91.7% for free from hospitalization by HF. Cluster 10 (6.0% of the total), which is co-morbid disorders of all four primary components, showed the worst survival rate of 39.1% for cardiovascular death, 68.9% for non-cardiovascular death, 23.9% for all-cause death, and 28.1% for free from hospitalization by HF.. These results suggest the potential applicability of the machine leaning approach, providing useful clinical prognostic information to stratify complex heterogeneity in patients with HF.

Topics: Atrial Fibrillation; Chronic Disease; Heart Failure; Humans; Machine Learning; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

Chronic heart failure (CHF) is a complicated syndrome caused by structural and functional abnormalities. Long noncoding RNA (LncRNA) lung cancer-associated transcript 1 (LUCAT1) downregulation inhibits cardiomyocyte apoptosis. This study aimed to measure LUCAT1 expression in patients with CHF and to explore its clinical value on CHF diagnosis and prognosis. A total of 94 patients with CHF and 90 participants without CHF were registered, followed by recording of their clinical characteristics and grading of their cardiac function. LUCAT1 expression in sera of patients with CHF and participants without CHF was detected. The correlation of LUCAT1 with brain natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) in patients with CHF and the diagnostic efficiency of LUCAT1, BNP, and LUCAT1 combined with BNP on patients with CHF were analyzed. Patients with CHF were treated with conventional drugs and followed up. The LUCAT1 expression in patients with CHF was lower than that in participants without CHF and was downregulated with the increase of New York Heart Association stage. LUCAT1 expression was negatively associated with BNP but positively associated with LVEF in the sera of patients with CHF. The receiver operating characteristic curve of LUCAT1 combined with BNP had better result than that of LUCAT1 and BNP alone. Low LUCAT1 expression indicated poor prognosis of patients with CHF and was an independent prognostic factor for the survival of patients with CHF. To summarize, low lncRNA LUCAT1 expression might help diagnose and predict the poor prognosis of CHF.

Topics: Chronic Disease; Heart Failure; Humans; Lung Neoplasms; Natriuretic Peptide, Brain; Prognosis; RNA, Long Noncoding; Stroke Volume; Ventricular Function, Left

Circulating secretoneurin (SN) concentrations have been found to provide prognostic information in patients with acute heart failure. We wanted to assess whether SN would improve prognostication also in patients with chronic heart failure (HF) in a large multicenter trial.. We measured plasma SN concentrations at randomization (n = 1224) and after 3 months (n = 1103) in patients with chronic, stable HF from the GISSI-HF study. The co-primary endpoints were (1) time to death or (2) admission to hospital for cardiovascular reasons.. Mean age was 67 years and 80% were male. Median (quartile 1-3) SN concentrations were 42.6 (35.0-62.8) pmol/L on randomization and 42.0 (34.5-53.1) pmol/L after 3 months, which are higher than SN concentrations in healthy subjects. Higher SN concentrations at randomization were associated with lower body-mass index (BMI), lower systolic blood pressure, lower estimated glomerular filtration rate (eGFR), higher B-type natriuretic peptide (BNP) concentrations, and diagnosis of chronic obstructive pulmonary disease. During median follow-up of 3.9 years, 344 patients (27.0%) died. After adjusting for age, sex, left ventricular ejection fraction, BMI, functional class, ischemic etiology, heart rate, blood pressure, eGFR, bilirubin, comorbidities, and BNP concentrations, logarithmically transformed SN concentrations on randomization were associated with mortality (HR 2.60 (95% CI 1.01-6.70), p = 0.047). SN concentrations were also associated with admission to hospital for cardiovascular reasons, but the association was attenuated and no longer significant in multivariable analysis.. Plasma SN concentrations provided incremental prognostic information to established risk indices and biomarkers in a large cohort of chronic HF patients.

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Function, Left

Regional handling and the prognostic performance of insulin-like growth factor binding protein (IGFBP)-7, in contrast or in combination with other candidate biomarkers, in chronic heart failure (CHF) remain uncertain.. The authors investigated the regional handling of plasma IGFBP-7 and its association with long-term outcomes in CHF in comparison with selected circulating biomarkers.. Plasma concentrations of IGFBP-7, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor-15, and high-sensitivity C-reactive protein were measured prospectively in a cohort with CHF (n = 863). The primary outcome was the composite of heart failure (HF) hospitalization or all-cause mortality. In a separate non-HF cohort (n = 66) undergoing cardiac catheterization, transorgan gradients of plasma IGFBP-7 concentrations were evaluated.. Among 863 patients (age 69 ± 14 years, 30% female, 36% HF with preserved ejection fraction), IGFBP-7 (median: 121 [IQR: 99-156] ng/mL) related inversely to left ventricular volumes but directly to diastolic function. Above the optimal cutoff, IGFBP-7 ≥110 ng/mL was independently associated with 32% increased hazard of the primary outcome: 1.32 (95% CI: 1.06-1.64). Among the 5 markers, IGFBP-7 had the highest hazard for a proportional increment in plasma concentrations independent of HF phenotype in single- and double-biomarker models, and provided incremental prognostic value beyond clinical predictors plus NT-proBNP, high-sensitivity troponin-T, and high-sensitivity C-reactive protein (P < 0.05). Assessment of regional concentrations indicated renal secretion of IGFBP-7 in contrast to renal extraction of NT-proBNP, possible cardiac extraction of IGFBP-7 in contrast to secretion of NT-proBNP, and common hepatic extraction of both peptides.. Transorgan regulation of IGFBP-7 is distinct from NT-proBNP. Circulating IGFBP-7 independently predicts adverse outcomes in CHF with a strong prognostic performance when compared with other well-recognized cardiac-specific or noncardiac prognostic markers.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Chronic Disease; Female; Heart Failure; Humans; Insulin-Like Growth Factor Binding Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Troponin T

To explore the influential elements of urinary kidney injury molecule-1 levels in chronic heart failure, and to judge its ability to predict 90-day rehospitalisation.. The cross-sectional case-control study was conducted from November 2020 to April 2021, at Hanzhong Central Hospital, China, and comprised adult patients having chronic heart failure with normal renal function in group A and healthy subjects in control group B. Patients in group A received anti-heart failure therapy for 1 week in hospital and were followed up for 90 days after discharge. Blood pressure (BP), kidney injury molecule-1, creatinine and serum pro- B-type natriuretic peptide levels were evaluated at baseline and 1 week after treatment in group A, while the samples were collected only at baseline in the control group B. Data was analysed using SPSS 22.. Of the 102 subjects, 68(66.6%) were in group A; 44(64.7%) males and 24 (35.3%) females with mean age 62.38±9.51 years. The remaining 34(33.3%) subjects were in group B; 21(61.7%) males and 13(38.2%) females with mean age vs. 58.82±8.11 years. The urinary kidney injury molecule-1 level in group A was essentially on the increase compared to group B (p<0.05). After 1 week of treatment, the kidney injury molecule-1 level decreased compared to the baseline value in group A (p<0.05). Diastolic blood pressure and pro-B-type natriuretic peptide were the determinants of urinary kidney injury molecule-1 level, and urinary kidney injury molecule-1 level before discharge was significantly associated with rehospitalisation within 90 days (p<0.05).. Urinary kidney injury molecule-1 level before discharge was a significant predictor of rehospitalisation within 90 days, and diastolic blood pressure and pro-B-type natriuretic peptide levels were the influencing factors of urinary kidney injury molecule-1. Also, urinary kidney injury molecule-1 levels were significantly raised in chronic heart failure.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

Topics: Adult; Aged; Anemia; Angioplasty, Balloon; Antihypertensive Agents; Atrial Pressure; Body Mass Index; Chronic Disease; Clinical Decision Rules; Endarterectomy; Endothelin Receptor Antagonists; Enzyme Activators; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Nomograms; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prognosis; Proportional Hazards Models; Pulmonary Artery; Pulmonary Embolism; Pulmonary Wedge Pressure; Pyrazoles; Pyrimidines; Reproducibility of Results; Survival Rate

The aim of this study was to establish age-specific and sex-specific cut-off values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-troponin T) in healthy subjects and assess cardiac biomarkers as screening tools for subclinical heart failure (HF) in a general population.. Altogether, 1936 participants were randomly selected from the general population Tromsø 7 study in Northern Norway. Diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) of cardiac markers for echocardiographically defined subclinical HF was evaluated. The receiver-operating characteristic analysis showed that areas under the curve were relatively low (under 0.75) for both NT-proBNP and hs-troponin T, suggesting that the diagnostic accuracy of these biomarkers for subclinical HF was not excellent, especially for mild forms of HF and younger age group 40-49 years. Sex-specific and age-specific cut-offs for hs-troponin T (99th percentiles) and NT-proBNP (97.5th percentiles) were established in healthy subjects from the same general population. The sex-specific and age-specific cut-offs for NT-proBNP had higher specificity for subclinical HF compared with the previously established single cut-off 125 pg/mL. Age-specific cut-off for hs-troponin T (18 ng/L) for men ≥60 years had also higher specificity than the single cut-off 14 ng/L. These cut-offs had high specificity, but low sensitivity, that makes hs-troponin T and NT-proBNP good biomarkers to rule in HF in case of a positive test, but not good enough to rule out all unrecognized HF due to false negative results.. N-terminal pro-brain natriuretic peptide and hs-troponin T are suboptimal screening tools for subclinical HF in a general population due to low sensitivity.

Topics: Adult; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

What is the central question of this study? What are the cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies, and is mitophagy involved? What is the main finding and its importance? Moderate-intensity continuous training may be the 'optimum' modality for improving cardiac structure and function in ischaemic heart failure, while both moderate-intensity continuous training and high-intensity interval training were suitable for pressure-overload heart failure. Various mitophagy pathways, especially parkin-dependent pathways, participated in the protective effects of exercise on heart failure.. The cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies and whether mitophagy is involved remain elusive. In the current research, left anterior descending ligation and transverse aortic constriction surgeries were used to establish mouse models of heart failure, followed by 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). The results showed that for ischaemic heart failure MICT significantly improved ejection fraction (P < 0.05) and fractional shortening (P < 0.05), mitigated left ventricular end-systolic dimension (P < 0.01), decreased brain natriuretic peptide (P < 0.0001) and mitigated fibrosis (P < 0.0001), while HIIT only decreased brain natriuretic peptide (P < 0.0001) and fibrosis (P < 0.0001). For pressure-overload heart failure, both MICT and HIIT significantly increased ejection fraction (P < 0.0001) and fractional shortening (MICT: P < 0.001, HIIT: P < 0.0001), and reduced left ventricular end-diastolic and end-systolic dimensions, brain natriuretic peptide (P < 0.0001), and fibrosis (MICT: P < 0.01, HIIT: P < 0.0001); HIIT was even better in reducing brain natriuretic peptide. Myocardial autophagy and mitophagy were compromised in heart failure, and the exercises improved myocardial autophagic flux and mitophagy inconsistently in heart failure with different aetiologies. Significant correlations were found between multiple mitophagy pathways and the cardioprotection of the exercises. Collectively, MICT may be the 'optimum' modality for ischaemic heart failure, while both MICT and HIIT (especially HIIT) were suitable for pressure-overload heart failure. Exercises differently improved myocardial autophagy/mitophagy, and multiple mitophagy-related pathways were closely implicated in cardioprotection of exercises for chronic heart failure.

Topics: Animals; Chronic Disease; Fibrosis; Heart Failure; High-Intensity Interval Training; Mice; Mitophagy; Natriuretic Peptide, Brain

Heart failure is an important mortality and morbidity. In this study, we aimed to investigate the frequency of vitamin D deficiency in chronic heart failure patients who live in a sunny region and to evaluate its relationship with the New York Heart Association (NYHA) functional classes.. The study included 657 patients. Demographic clinical, and laboratory parameters were evaluated according to the NYHA classes. Ordinal regression analysis was used to determine the parameters defining the NYHA class.. The median serum 25-hydroxy-vitamin D [25(OH)D] level of study population was 16.88 ng/mL. It was 30 ng/mL. 25(OH)D level was positively correlated with eGFR, calcium, albumin, hemoglobin, transferrin saturation, serum iron, while a negative correlation was found with heart rate, parathormon, NT-proBNP, and CRP. Together with dereased ß blocker use, increase in N-terminal pro-brain natriuretic peptide levels and left atrial diameter, a decrease in vitamin D level (OR: 0.970, 95% CI: 0.945-0996, P=.024) was independently associated with an increase in the New York Heart Association class.. Vitamin D deficiency and insufficiency are common in patients with chronic heart failure, and vitamin D level is an important determinant of the NYHA functional class in patients with heart failure.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; New York; Peptide Fragments; Vitamin D; Vitamin D Deficiency

Objectives • This study aimed to assess the diagnostic value of serum brain natriuretic peptide (BNP), cathepsin S (Cat S), serum soluble ST2 receptor (sST2), platelet reactive protein-1 (TSP-1) and interleukin-11 (IL-11) in patients with chronic heart failure (CHF).. Materials and Methods • A total of 112 patients admitted to in our hospital with HF were enrolled as the HF group and 120 healthy people undergoing physical examination were assigned to the control group. The serum levels of Cat S, TSP-1, IL-11, sST2 and BNP were measured and compared in the subgroups categorized according to New York Heart Association (NYHA) Functional Classification. Pearson correlation was applied to analyze the correlation between serum Cat S, TSP-1, IL-11, sST2 and BNP and NYHA functional class. Moreover, multivariate logistic regression was used to analyze the HF influencing factors.. Results • No correlation was found between the 2 groups in terms of general information, such as age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, smoking and heart rate (P > .05). The left ventricular ejection fraction (LVEF) in the HF group was lower than in the control group, while the level of LV end diastolic dimension (LVEDD) and left ventricular end diastolic volume (LVEDV) was significantly higher (P < .05). The levels of Cat S, TSP-1, sST2, IL-11 and BNP in the HF group were higher than in the control group (P < .05). The levels of Cat S, TSP-1, sST2, IL-11 and BNP in the grade IV group were higher than those in the grade II and III groups (P < .05). Serum Cat S, TSP-1, IL-11, sST2 and BNP levels were positively correlated with NYHA functional class (R = 0.568, 0.409, 0.472, 0.547, 0.632, respectively) (P < .001). Multivariate logistic regression analysis demonstrated that LVEF, LVEDD, LVEDV, Cat S, TSP-1, IL-11, sST2 and BNP were independent markers of CHF.. Conclusion • Abnormal Cat S, TSP-1, IL-11, sST2 and BNP levels were found in patients with CHF, and were highly associated with the cardiac function grades of CHF. Therefore, serum Cat S, TSP-1, IL-11, sST2 and BNP levels can serve as independent markers for CHF.

Topics: Biomarkers; Cathepsins; Chronic Disease; Heart Failure; Humans; Interleukin-11; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Thrombospondin 1; Ventricular Function, Left

To define plasma concentrations, determinants, and optimal prognostic cut-offs of soluble suppression of tumorigenesis-2 (sST2), high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in women and men with chronic heart failure (HF).. Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs-cTnT, and NT-proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all-cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs-cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT-proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut-off was lower in women for sST2 (28 vs. 31 ng/mL) and hs-cTnT (22 vs. 25 ng/L), while NT-proBNP cut-off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex-specific cut-offs improved risk prediction compared with the use of previously standardized prognostic cut-offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs-cTnT than sST2 or NT-proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex-specific cut-off of hs-cTnT for the endpoint of 5 year cardiovascular death.. In patients with chronic HF, concentrations of sST2 and hs-cTnT, but not of NT-proBNP, are lower in women. Lower sST2 and hs-cTnT and higher NT-proBNP cut-offs for risk stratification could be used in women.

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Troponin T; Ventricular Function, Left

High‑sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT‑ proBNP) are known markers of cardiac injury. However, their role in predicting the severity of COVID‑19 remains to be investigated.. We aimed to analyze the association between hs‑cTnT and NT-proBNP levels and in hospital mortality in patients with COVID‑19, with emphasis on those with concomitant chronic heart failure (CHF).. A total of 1729 consecutive patients with COVID‑19 were enrolled. Demographic data, laboratory parameters, and clinical outcomes (discharge or death) were analyzed. Receiver operating characteristic (ROC) and logistic regression analyses were performed to evaluate the association between hs‑cTnT and NT-proBNP values and the risk of death.. Evaluation of hs‑cTnT was performed in 1041 patients, while NT-proBNP was assessed in 715 individuals. CHF was present in 179 cases (10.4% of the cohort). Median values of hs‑cTnT and NT-proBNP and in‑hospital mortality were higher in CHF patients than in those without CHF. Among patients without CHF, mortality was the highest in those with hs‑cTnT or NT-proBNP values in the fourth quartile. In ROC analysis, hs‑cTnT equal to or above 142 ng/l and NT-proBNP equal to or above 969 pg/ml predicted in‑hospital death. In patients without CHF, each 10-ng/l increase in hs-cTnT or 100-pg/ml increase in NT‑proBNP was associated with a higher risk of death (odds ratio [OR], 1.01 and OR, 1.02, respectively; P <0.01 for both).. The level of hs‑cTnT or NT-proBNP predicts in hospital mortality in COVID-19 patients. Both hs‑cTnT and NT-proBNP should be routinely measured on admission in all patients hospitalized due to COVID‑19 for early detection of individuals with an increased risk of in hospital death, even if they do not have concomitant heart failure.

Topics: Biomarkers; Chronic Disease; COVID-19; Heart Failure; Hospital Mortality; Humans; Natriuretic Peptide, Brain; ROC Curve

Aim    To test a hypothesis that increased values of red cell distribution width (RDW) in patients with chronic heart failure (CHF) can be related with low exercise tolerance.Material and methods    102 patients were evaluated who had CHF with mid-range and reduced left ventricular ejection fraction (LV EF) without anemia (72% men, mean age 66±10.2 years). Cardiopulmonary stress test (CPST), echocardiography, 6‑min walk test (6MWT), blood count, and measurements of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and serum iron were performed.Results    The average LV EF was 39±8.7 %; the peak oxygen consumption (VO2peak) was 13.7±4.8 ml /kg /min; and the median NT-pro-BNP was 595.3 pg /ml (Q1-3 1443-2401). RDW variables, including the RDW coefficient of variation (RDW-CV) and RDW standard deviation (RDW-SD), were not significantly related with serum iron or hemoglobin concentrations. A one-factor linear regression analysis showed a significant correlation of VO2peak with RDW-SD (р=0.039). A multivariate linear regression analysis with adjustments for LV EF, hemoglobin concentration, and age did not reveal any significant correlation of VO2peak with RDW variables. The distance covered in the 6MWT was significantly associated with RDW-CV both in the one-factor analysis and with adjustments for LV EF, hemoglobin and serum iron concentrations, and age.Conclusion    This study showed that high RDW values in CHF patients without anemia predicted low exercise tolerance regardless of the age, LV systolic function, and hemoglobin and serum iron concentrations. A 16% increase in RDW-CV significantly decreased the likelihood of covering a distance longer than 360 m during 6 min.

Topics: Aged; Chronic Disease; Erythrocyte Indices; Exercise Tolerance; Female; Heart Failure; Hemoglobins; Humans; Iron; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.. The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.. Of 5,988 study participants, 5,986 (99.9%) and 5,825 (97.3%) had available baseline NT-proBNP and hs-cTnT; postbaseline NT-proBNP was also available. Baseline characteristics were expressed by biomarker quartiles. The effect of empagliflozin on cardiovascular death/ HF hospitalization, the individual components, total HF hospitalizations, slope of decline of estimated glomerular filtration rate (eGFR), and a composite renal endpoint were examined across biomarker quartiles. Change in NT-proBNP across study visits as a function of treatment assignment was also assessed.. Higher baseline NT-proBNP and hs-cTnT concentrations were associated with more comorbidities and worse HF severity. Incidence rates for cardiac and renal outcomes were 2- to 5-fold higher among those in the highest vs lowest NT-proBNP or hs-cTnT quartiles. Empagliflozin consistently reduced the risk for cardiovascular events and reduced slope of eGFR decline across NT-proBNP or hs-cTnT quartiles. Empagliflozin treatment modestly lowered NT-proBNP; by 100 weeks, the adjusted mean difference in NT-proBNP from placebo was 7%. Increase in NT-proBNP from baseline to 12 weeks was strongly associated with risk of cardiovascular death/HF hospitalization.. The benefit of empagliflozin on cardiac outcomes and decline of eGFR is preserved across the wide range of baseline NT-proBNP and hs-cTnT evaluated. Empagliflozin modestly reduces NT-proBNP in HF with preserved ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).

Topics: Biomarkers; Chronic Disease; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin T

To analyze the combination clinical value of plasma brain natriuretic peptide and serum glycated hemoglobin (HbAlc) in chronic pulmonary heart disease.. A total of 200 patients with chronic pulmonary heart disease admitted to our hospital from January 2021 to January 2022 were selected as the observation group, and 200 healthy subjects were selected as the control group during the same period. All subjects were examined by an ECG vector map and plasma BNP, and HbAlc levels were detected to analyze the value and clinical significance of each index in single diagnosis and combined diagnosis.. Plasma BNP and HbAlc levels in the observation group were significantly higher than those in the control group (. In the diagnosis of chronic pulmonary heart disease, the combination of plasma BNP and HbAlc can effectively improve the diagnostic specificity and sensitivity, as well as improve the area under the ROC curve.

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Pulmonary Heart Disease; ROC Curve; Sensitivity and Specificity

Biomarker-driven prognostic models incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We aimed to generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved.. Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, (iii) cardiovascular death, and (iv) HF hospitalization. PARAGON-HF was used as a validation cohort. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last hospitalization, New York Heart Association (NYHA) class III or IV, history of chronic obstructive pulmonary disease (COPD), insulin-treated diabetes, low haemoglobin, and a longer time since HF diagnosis were key predictors (eight variables, all p < 0.001). The consequent primary outcome risk score discriminated well (c-statistic = 0.75) with patients in the top 10th of risk having an event rate >22× higher than those in the bottom 10th. A model for HF hospitalization alone had even better discrimination (c = 0.79). Empagliflozin reduced the risk of cardiovascular death or hospitalization for HF in patients across all risk levels. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality followed by history of COPD, low albumin, older age, left ventricular ejection fraction ≥50%, NYHA class III or IV and insulin-treated diabetes (eight variables, all p < 0.001). The mortality risk model had similar discrimination for all-cause and cardiovascular mortality (c-statistic = 0.72 for both). External validation provided c-statistics of 0.71, 0.71, 0.72, and 0.72 for the primary outcome, HF hospitalization alone, all-cause death, and cardiovascular death, respectively.. The combination of NT-proBNP and hs-cTnT along with a few readily available clinical variables provides effective risk discrimination both for morbidity and mortality in patients with HFpEF. A predictive tool-kit facilitates the ready implementation of these risk models in routine clinical practice.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Insulins; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Disease, Chronic Obstructive; Stroke Volume; Ventricular Function, Left

This study aimed to analyze the correlation between the level of brain natriuretic peptide (BNP) and the condition and prognosis of chronic heart failure (CHF). For this purpose, between January 2017 and July 2020, we recruited a total of 120 CHF patients who were treated in Cangzhou Central Hospital into this study, consisting of 40 patients in NYHA II, 40 in NYHA III and 40 in NYHA IV, and simultaneously, 40 subjects with normal heart function were enrolled into the control group. General data were collected from the patients and subjects, and laboratory tests regarding the BNP level, LVEDD and LVEF were carried out. Correlation between plasma level of BNP and the evaluation of condition and prognosis of CHF was also analyzed. For further evaluation, the expression of BNP gene expression was considered in the femoral blood of participants by the Real-time PCR technique. The results showed that comparison over the clinical data of subjects among these groups showed no significant difference (P > 0.05). In the research group, the averages of LVEDD and BNP in plasma were (58.53±3.75) mm and (5089.86±22.39) pg/mL, significantly higher than those in the control group, while the LVEF was (45.66±3.42) %, which was lower than that in the control group (all P < 0.05). For the subgroup comparison, as the NYHA class augmented, patients also had a significant increase in the mortality rate and the difference among subgroups had statistical significance (P < 0.05). Furthermore, with 442 pg/mL as a critical point for BNP, patients in the research group were further divided into the BNP>442 pg/mL group and BNP ≤442pg/mL group, and the statistical analysis revealed that in the BNP>442 pg/mL group, the incidence rate of cardiovascular events, re-hospitalization rate and mortality rate were 53.53%, 14.14% and 7.07%, which were all significantly higher than those in the BNP ≤ 442 pg/mL group (all P < 0.05). Also, BMP gene expression was increased in NYHA II, NYHA III, and NYHA IV groups compared to the control group. However, this increase was statistically significant in the NYHA III group (P <0.05) and in the NYHA IV group (P <0.01) compared to the control group. In conclusion, the level of BNP in plasma can reflect the condition of CHF and is critical to the clinical diagnosis, treatment and prognosis evaluation and evaluation of the BNP gene confirmed the result. Thus, it is worth being promoted in clinical practice.

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Plasma

To study the efficacy and safety of exogenous phosphocreatine (EF) in patients with chronic heart failure (CHF).. The all-Russian prospective observational study BYHEART included 842 patients who were treated with EF. Before and after the course of EF therapy, the following studies were conducted: a questionnaire on the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and a clinical condition assessment scale (SHOCK), transthoracic echocardiography with an assessment of the left ventricular ejection fraction, a 6-minute walk test, determination of the level of pro-natriuretic N-terminal peptide (NT-proBNP), glomerular filtration rate. All patients before the course of EF received long-term optimal drug therapy of CHF.. Statistical analysis was carried out in the general group of patients (n=842), as well as in groups of patients A (n=418, the course of treatment of EF is less than 20 g /course) and group B (n=424, the course of treatment of EF is greater than or equal to 20 g/course). The results obtained demonstrate a positive effect of the use of the course of therapy of EF in patients with CHF on the quality of life (QOL), reverse left ventricular remodeling, functional class of CHF, as well as the concentration of NT-pro-BNP, especially in the group of patients who received more than 20 grams of the medication.. The use of EF is a promising pharmacological method of treatment in addition to optimal drug therapy in patients with CHF.. Цель. Изучить эффективность и безопасность экзогенного фосфокреатина (ЭФ) у пациентов с хронической сердечной недостаточностью (ХСН). Материалы и методы. В общероссийское проспективное наблюдательное исследование BYHEART включены 842 пациента, которым проведен курс лечения ЭФ. До курса терапии ЭФ и после проводились следующие исследования: анкетирование по Миннесотскому опроснику качества жизни больных с ХСН (MHFLQ) и шкале оценки клинического состояния, трансторакальная эхокардиография с оценкой фракции выброса левого желудочка, тест 6-минутной ходьбы, определение уровня пронатрийуретического N-концевого пептида (NT-proBNP), скорости клубочковой фильтрации. Все пациенты до курса ЭФ получали длительную оптимальную медикаментозную терапию ХСН. Результаты. Статистический анализ проводился в общей группе пациентов (n=842), а также в группах пациентов А (n=418, ЭФ20 г на курс) и Б (n=424, ЭФ20 г на курс). Полученные результаты демонстрируют положительное влияние курса терапии ЭФ у пациентов с ХСН на качество жизни, обратное ремоделирование левого желудочка, функциональный класс ХСН, а также концентрацию NT-proBNP, особенно в группе больных, получивших 20 г или более препарата. Заключение. Применение ЭФ является перспективным фармакологическом методом лечения в дополнение к оптимальной медикаментозной терапии у пациентов с ХСН.

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Phosphocreatine; Quality of Life; Stroke Volume; Ventricular Function, Left

Iron deficiency is frequent in patients with chronic heart failure (CHF) with a prevalence of 50%, and its frequency varies depending on the study groups. The presence of iron deficiency limits erythropoiesis, leading to the development of anemia over time in patients with CHF, regardless of gender, race, and left ventricular ejection fraction (LVEF). Observational studies demonstrate a higher prevalence of iron deficiency in women and in patients with higher NYHA (New York Heart Association) functional class, decreased LVEF, increased brain natriuretic peptide (NT-proBNP), or increased high-sensitivity C-reactive protein. Iron deficiency and anemia in patients with CHF are independently associated with a decreased exercise capacity, hospitalizations for CHF, an increase in overall mortality and mortality from cardiovascular diseases. The clinical significance of iron deficiency requires the need to diagnose iron metabolism in all patients with CHF. Current guidelines for the diagnosis and treatment of CHF indicate the need to determine the level of ferritin and saturation of transferrin in all patients with a suspected diagnosis of heart failure. The use of oral iron therapy in patients with CHF demonstrates its low efficacy in correcting this condition according to the clinical trials. At the same time the use of intravenous iron therapy is safe and improves symptoms, exercise capacity and quality of life in patients with heart failure with reduced ejection fraction and iron deficiency, which has been shown both in international placebo-controlled trials and meta-analyses. The use of iron carboxymaltose should improve CHF symptoms, exercise capacity and quality of life in patients with CHF and LVEF45%. Intravenous iron therapy has also been shown to reduce readmissions for CHF in patients with an LVEF50% who have recently been hospitalized for worsening CHF.. При хронической сердечной недостаточности (ХСН) дефицит железа встречается в среднем у 1/2 пациентов, и его частота различается в зависимости от исследуемых групп. Наличие дефицита железа ограничивает эритропоэз, что приводит к развитию анемии с течением времени у пациентов с ХСН, независимо от пола, расы и фракции выброса левого желудочка (ФВЛЖ). Наблюдательные исследования демонстрируют более высокую распространенность железодефицита у женщин при повышении функционального класса ХСН по шкале Нью-Йоркской кардиологической ассоциации, снижении ФВЛЖ, повышении уровня мозгового натрийуретического пептида и высокочувствительного С-реактивного белка. Дефицит железа и анемия у пациентов с ХСН независимо связаны со снижением способности к физической нагрузке, повторными госпитализациями по поводу ХСН, повышением общей смертности и смертности от сердечно-сосудистых заболеваний. Клиническая значимость дефицита железа диктует необходимость диагностики показателей обмена железа у всех пациентов с ХСН. Современные рекомендации по диагностике и лечению ХСН указывают на необходимость определения уровня ферритина и насыщения трансферрина у всех пациентов с подозрением на диагноз сердечной недостаточности. Исследования по применению пероральных препаратов для лечения дефицита железа у пациентов с ХСН демонстрируют их низкую эффективность для коррекции данного состояния. В то же время добавление препаратов внутривенного железа к терапии ХСН безопасно, улучшает симптоматику, переносимость физических нагрузок и качество жизни пациентов с ХСН со сниженной ФВЛЖ и дефицитом железа, что показано как в международных плацебо-контролируемых исследованиях, так и в метаанализах. В настоящее время назначение карбоксимальтозата железа следует рассматривать для улучшения симптомов ХСН, повышения толерантности к физической нагрузке и качества жизни у пациентов с ХСН и ФВЛЖ45%. Также терапия внутривенным железом способствует снижению повторных госпитализаций по поводу ХСН у пациентов с ФВЛЖ50%, недавно госпитализированных по поводу ухудшения ХСН.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Chronic Disease; Controlled Clinical Trials as Topic; Female; Ferritins; Heart Failure; Humans; Iron; Iron Deficiencies; Male; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Observational Studies as Topic; Quality of Life; Stroke Volume; Transferrins; Ventricular Function, Left

Background Acute heart failure is the most frequent cause of unplanned hospital admission in elderly patients. Various biomarkers have been evaluated to better assess the status of these patients and prevent decompensation. Recently, voice has been suggested as a cost-effective and noninvasive way to monitor disease progression. This study evaluates speech and pause alterations in patients with acute decompensated and stable heart failure. Specifically, we aim to identify a vocal biomarker that could be used to monitor patients with heart failure and to prevent decompensation. Methods and Results Speech and pause patterns were evaluated in 68 patients with acute and 36 patients with stable heart failure. Voice recordings were performed using a web-browser based application that consisted of 5 tasks. Speech and pause patterns were automatically extracted and compared between acute and stable patients and with clinical markers. Compared with stable patients, pause ratio was up to 14.9% increased in patients with acute heart failure. This increase was largely independent of sex, age, and ejection fraction and persisted in patients with lower degrees of edema or dyspnea. Furthermore, pause ratio was positively correlated with NT-proBNP (N-terminal pro-B-type natriuretic peptide) after controlling for acute versus stable heart failure. Collectively, our findings indicate that the pause ratio could be useful in identifying acute heart failure, particularly in patients who do not display traditional indicators of decompensation. Conclusions Speech and pause patterns are altered in patients with acute heart failure. Particularly, we identified pause ratio as an easily interpretable vocal biomarker to support the monitoring of heart failure decompensation.

Topics: Aged; Biomarkers; Chronic Disease; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Speech; Stroke Volume

BACKGROUND Scientific data regarding transthoracic impedance cardiography (ICG) parameters and its utility in patients with heart failure (HF) remains controversial. This study from a single center in Lithuania aimed to evaluate the role of ICG in the diagnosis and outcome evaluation of patients who were admitted to the hospital due to HF exacerbation. MATERIAL AND METHODS The sample consisted of 301 consecutive patients with a previous chronic HF diagnosis (166 men, 135 women) hospitalized for HF flare-ups. ICG data were compared to other noninvasive HF diagnostic tests. Data about patient outcomes were gathered from the Lithuanian Medical Record Database. RESULTS A weak correlation of amino-terminal pro-brain natriuretic peptide (NT-proBNP) with thoracic fluid content (TFC) and thoracic fluid content index (TFCI) was found (r=0.204, P<0.001 and r=0.207, P<0.001, respectively). There was weak to moderate correlation of 6-min walk distance with main ICG data. There was weak correlation between left ventricular ejection fraction (LVEF) with TFCI (r=-0.163, P=0.005), systolic index (r=-0.137, P=0.017), and systolic time ratio (r=0.236, P<0.001). By multivariate Cox proportional analysis, the following parameters were independently associated with cardiac death (P<0.001): NT-proBNP ≥425.5 pmoL/L (hazard ratio (HR), 5.104, 95% confidence interval (CI) 3.326-7.832), TFC ≥36.9 1/kOhm (HR, 4.604, 95% CI 2.701-7.849), LVEF ≤40% (HR, 4.942, 95% CI 2.8256-8.647). CONCLUSIONS The combination of non-invasively measured TFC, LVEF, and NT-proBNP showed great prognostic value for predicting readmissions and cardiac death in patients with HF.

Topics: Biomarkers; Cardiography, Impedance; Chronic Disease; Female; Heart Failure; Humans; Lithuania; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Ventricular Function, Left

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Topics: Aged; Anaerobic Threshold; Angiopoietin-Like Protein 2; Angiopoietin-like Proteins; Biomarkers; Blood Proteins; Body Composition; C-Reactive Protein; Cardiac Rehabilitation; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Echocardiography; Exercise Tolerance; Female; Hand Strength; Heart Failure; Humans; Inflammation; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Cardiac cachexia (CC) is an unfavorable metabolic syndrome leading to exacerbation of chronic heart failure (CHF) and a higher risk of death. The main factor contributing to the development of cachexia is the ongoing inflammatory process mediated by genes (e.g. Integrin Subunit Alpha M-ITGAM). The study aimed to assess the relationship between a single nucleotide polymorphism (SNP) -323G > A of the ITGAM and the occurrence of nutritional disorders in patients with CHF. 157 CHF patients underwent clinical and nutritional screening. Body composition was evaluated by bioelectrical impedance analysis (BIA). Patients with cachexia were characterized by significantly lower weight, body mass index (BMI), lower fat mass (FM), albumin, and hemoglobin. Lower values of BIA parameters: capacitance of membrane (Cm), phase angle (PA), and impedance ratio (Z200/Z5) were noted in women. Those patients demonstrated significantly higher values of creatinine, c-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and pulmonary artery systolic pressure (PASP). A significantly higher risk of cachexia was reported in patients: aged ≥ 74 years (OR 3.55), with renal failure (OR 3.75), New York Heart Association classification (NYHA) III-IV (OR 2.83), with moderate or severe malnutrition according to the score of subjective global assessment (SGA) (OR 19.01) and AA genotype of ITGAM gene (OR 2.03). Determination of the -323G > A SNP in the ITGAM may prove to be a useful marker (after confirmation in further studies and appropriate validation) in the assessment of the risk of nutritional disorders in patients with CHF.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Composition; Body Mass Index; Cachexia; CD11b Antigen; Chronic Disease; Electric Impedance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide

The previous studies have shown that plasma chitotriosidase (CHIT) levels increase in many diseases with inflammation. However, there are no reported studies investigating the relationship between CHIT and chronic heart failure (CHF) which is an inflammatory process. Therefore, we aimed to investigate the role of CHIT in diagnosis and severity of CHF in this study. 36 patients (50% male, mean age 63.17±10.18 years) with left ventricular ejection fraction <40% and 27 controls (44% male, mean age 61.33±8.73 years) were included in this study. Patients with CHF were divided into two groups as ischemic heart failure (IHF) and non-ischemic heart failure (NIHF) according to the underlying etiology. Plasma CHIT and N-terminal pro brain natriuretic peptide (NT-proBNP) levels were measured by ELISA method. Plasma CHIT and NT-proBNP levels were higher in patients with CHF than in controls (CHIT 931.25±461.39 ng/mL, 232.79±61.28 ng/mL, p<0.001; NT-proBNP, 595.31±428.11 pg/mL vs 78.13±30.47 pg/L; p<0.001). Also, the levels of these parameters increased in IHF compared with NIHF (CHIT, 1139.28±495.22 ng/mL, 671.22±237.21 ng/mL, p=0.002; NT-proBNP, 792.87±461.26 pg/mL vs 348.36±202.61 pg/mL, p=0.001) and there was a strong correlation between NT-proBNP and CHIT (r=0.969, p<0.001). According to this study findings, plasma CHIT level increases in CHF and its increased levels are correlated with NT-proBNP which is used diagnosis and prognosis of HF.

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Hexosaminidases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Frailty is common in patients with chronic heart failure (CHF) and is associated with poor outcomes. The natural history of frail patients with CHF is unknown.. Frailty was assessed using the clinical frailty scale (CFS) in 467 consecutive patients with CHF (67% male, median age 76 years, median NT-proBNP 1156 ng/L) attending a routine follow-up visit. Those with CFS > 4 were classified as frail. We investigated the relation between frailty and treatments, hospitalisation and death in patients with CHF.. 206 patients (44%) were frail. Of 291 patients with HF with reduced ejection fraction (HeFREF), those who were frail (N = 117; 40%) were less likely to receive optimal treatment, with many not receiving a renin-angiotensin-aldosterone system inhibitor (frail: 25% vs. non-frail: 4%), a beta-blocker (16% vs. 8%) or a mineralocorticoid receptor antagonist (50% vs 41%). By 1 year, there were 56 deaths and 322 hospitalisations, of which 25 (45%) and 198 (61%), respectively, were due to non-cardiovascular (non-CV) causes. Most deaths (N = 46, 82%) and hospitalisations (N = 215, 67%) occurred in frail patients. Amongst frail patients, 43% of deaths and 64% of hospitalisations were for non-CV causes; 58% of cardiovascular (CV) deaths were due to advancing HF. Among non-frail patients, 50% of deaths and 57% of hospitalisations were for non-CV causes; all CV deaths were due to advancing HF.. Frailty in patients with HeFREF is associated with sub-optimal medical treatment. Frail patients are more likely to die or be admitted to hospital, but whether frail or not, many events are non-CV.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Female; Frail Elderly; Frailty; Heart Failure; Hospital Mortality; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Stroke Volume

Inflammation is a hallmark of heart failure (HF) and among inflammatory biomarkers, the most studied remains the C-reactive protein (CRP). In recent years several biomarkers have emerged, such as sST2 and soluble urokinase-type plasminogen activator receptor (suPAR). This study set out to examine the relative importance of long-time prognostic strength of suPAR and the potential additive information on patient risk with chronic HF in comparison with pronostic value of CRP and sST2.. Demographics, clinical and biological variables were assessed in a total of 182 patients with chronic HF over median follow-up period of 80 months. Inflammatory biomarkers (i.e., CRP, sST2, and suPAR) were performed.. In univariate Cox regression analysis age, NYHA class, MAGGIC score and the five biomarkers (N-terminal pro brain natriuretic peptide [NT-proBNP], high-sensitive cardiac troponin T [hs-cTnT], CRP, sST2, and suPAR) were associated with both all-cause and cardiovascular mortality. In the multivariate model, only NT-proBNP, suPAR, and MAGGIC score remained independent predictors of all-cause mortality as well as of cardiovascular mortality. Risk classification analysis was significantly improved with the addition of suPAR particularly for all-cause short- and long-term mortality. Using a classification tree approach, the same three variables could be considered as significant classifier variables to predict all-cause or cardiovascular mortality and an algorithm were reported. We demonstrated the favorable outcome associated with patients with a low MAGGIC score and a low suPAR level by comparison to patients with low MAGGIC score but high suPAR values.. The main findings of our study are (1) that among the three inflammatory biomarkers, only suPAR levels were independently associated with 96-month mortality for patients with chronic HF and (2) that an algorithm based on clinical score, a cardiomyocyte stress biomarker and an inflammatory biomarker could help to a more reliable long term risk stratification in heart failure.

Topics: Biomarkers; C-Reactive Protein; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Receptors, Urokinase Plasminogen Activator; Troponin T

Brain natriuretic peptide is an established, surrogate follow-up marker, strongly correlated with heart failure severity. Several other biomarkers and tests are useful for assessing the prognosis of patients with HF, such as oxidized low-density lipoprotein antibodies and C-reactive protein. Some inflammatory cells, including monocytes, lymphocytes, and neutrophils, are involved in coronary heart disease and may be useful for prognosis also. This study assessed the potential usefulness of various laboratory biomarkers in predicting long-term outcomes and hospitalization among a cohort of outpatients with chronic, advanced HF.This retrospective, 18-year follow-up study included all patients admitted to the Heart Failure Outpatient Unit in our tertiary care medical center from 2000 through 2001 due to chronic HF. Excluded were patients with malignant disease, severe stroke, active inflammatory disease, or infection. At the first visit, blood was sampled for routine analysis and biomarkers NT-proBNP, C-reactive protein, myeloperoxidase, heat shock protein, and antibodies to oxidized low density lipoprotein. left ventricular ejection fraction and New York Heart Association class class were also established. Patients were followed every 3 months. Study endpoints were mortality or first hospitalization.Among 305 study patients, HF duration ranged from 2 months to 18 years. Mean follow-up was 9.1 ± 6 years. Mean time to first hospitalization was 60 ± 58.1 months, median = 38 (range 0-179). Mortality rate was 41%. Regression analysis showed New York Heart Association class, lymphocyte count and alkaline phosphatase were independent predictors of survival, with hazard ratios of 1.0, 0.973, and 1.006, respectively (P < .05).N-terminal pro-B-type natriuretic peptide, alkaline phosphatase, and lymphocyte count are important prognostic predictors for very long-term follow-up among patients with chronic HF.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Body Weight; C-Reactive Protein; Chronic Disease; Comorbidity; Female; Follow-Up Studies; Heart Failure; Heart Rate; Heat-Shock Proteins; Hematologic Tests; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Retrospective Studies; Sex Factors; Ventricular Function, Left

The presence of metabolic syndrome (MS) significantly increases the risk of developing cardiovascular diseases that lead to chronic heart failure (CHF). The values of NT-proBNP, ST-2, and CRP markers and their mutual correlations were studied in 37 patients with chronic heart failure (CHF) without metabolic syndrome (MS) (group 1) and 37 patients with CHF with MS (group 2). The aim of the study was to determine the features of their changes in patients with CHF complicated by MS, and to rank patients by assigning a rank value to the values of NTproBNP, ST2, and CRP concentrations. The average ST2 level was 51±24 ng/ml in group 1 and 62±27 ng/ml in group 2. The average values of CRP in group 1 were 23.1±5.3 mg/l, in group 2-33.0±4.4 mg/l (p<0.05). The NTproBNP level was 2413±1586 PG/ml and 2721±1635 PG/ml in groups 1 and 2, respectively. Correlations between the values of NTproBNP and ST2, NTproBNP and CRP were demonstrated. In the group of CHF with MS, compared with the group of CHF, there were significantly more patients with the most pronounced pathological levels of damage markers: the number of patients with a General rank of 6-9 in the group of CHF with MS was 59%, in the group of CHF without MS-38% (p<0.05). Of the 18 patients who died, 17 were among those who had an overall rank of 6 to 9, only 1 patient who died after hospitalization had an overall rank of 5. At the same time, among 22 patients who had improved CHF in the outcome of hospitalization, 18 patients had a total rank from 0 to 5, and in 4 patients of this category, the clinical manifestations of CHF remained virtually unchanged. The results of ranking the level of the studied laboratory markers indicate that they can be used as a predictor of various outcomes of CHF.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Laboratories; Metabolic Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

The prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with coronary artery disease (CAD) with different glucose status has not been established. This study sought to evaluate the significance of NT-proBNP in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) and normal left-ventricular systolic function (LVSF) according to different glucose status, especially in those with abnormal glucose metabolism.. A total of 8062 patients with CCS and normal LVSF were consecutively enrolled in this prospective study. Baseline plasma NT-proBNP levels were measured. The follow-up data of all patients were collected. Kaplan-Meier and Cox regression analyses were used to assess the risk of MACEs according to NT-proBNP tertiles stratified by glucose status.. Over an average follow-up of 59.13 ± 18.23 months, 569 patients (7.1 %) suffered from MACEs, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Kaplan-Meier analysis showed that high NT-proBNP levels had a significant association with MACEs in subjects with prediabetes mellitus (pre-DM) or DM, but not in patients with normoglycemia. Multivariate Cox regression analysis revealed that NT-proBNP remained an independent predictor of MACEs in patients with pre-DM [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.34-4.91] or DM (HR: 2.34, 95% CI: 1.32-4.16). Moreover, adding NT-proBNP to the original Cox model including traditional risk factors significantly increased the C-statistic by 0.035 in pre-DM and DM, respectively.. The present study indicated that NT-proBNP could well predict worse outcomes in dysglycemic patients with CCS and normal LVSF, suggesting that NT-proBNP may help with risk stratification in this population.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Chronic Disease; Coronary Artery Disease; Diabetes Mellitus; Disease Progression; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prediabetic State; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Syndrome; Systole; Time Factors; Ventricular Function, Left

Topics: Chronic Disease; Heart Failure; Humans; MicroRNAs; Natriuretic Peptide, Brain; Neprilysin; Serine Endopeptidases

Health-related quality of life (HRQoL) is impaired in patients with pulmonary hypertension (PH). The EmPHasis-10 and CAMPHOR questionnaires are developed to evaluate HRQoL specifically in patients with PH. Data on the longitudinal use of both questionnaires are still limited. We evaluated the longitudinal value of both questionnaires and established minimal clinically important differences (MCID).. Sixty-one treatment naïve pulmonary arterial hypertension or chronic thromboembolic patients were prospectively included. Patients were treated according to the current ESC/ERS guidelines. We compared EmPHasis-10 and CAMPHOR scores between baseline, 6 and 12 months of follow-up and evaluated the correlation between these scores and a 5-scale symptom severity score, 5-scale overall health score, NYHA-classification, 6 min walk test distance (6MWD), NT-proBNP and echocardiographic parameters.. After one year of treatment a significant reduction in EmPHasis-10 score and CAMPHOR QoL and symptoms domain score was observed. Moderate to good correlations were observed between the questionnaires and the overall-health and symptom severity score and 6MWD. No relevant correlations were seen between the questionnaires and NT-pro-BNP and echocardiographic parameters. EmPHasis-10 scores showed strong correlations with all CAMPHOR domains. The MCID for the EmPHasis-10 questionnaire was -8. The MCIDs for the CAMPHOR domains were: activity -3, symptoms -4, QoL -3.. The EmPHasis-10 and CAMPHOR questionnaires are valid tools for the longitudinal measurement of HRQoL in patients with PH. The much shorter EmPHasis-10 correlates well with the CAMPHOR domain scores and with the clinical endpoints and it may be easier to use in daily practice.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Reported Outcome Measures; Peptide Fragments; Pulmonary Arterial Hypertension; Pulmonary Embolism; Quality of Life; Surveys and Questionnaires; Time Factors; Walk Test

Among changes in demographics, aging is the most relevant cardiovascular risk factor. The prevalence of peripheral artery disease (PAD) is high in elderly patients and is associated with a worse prognosis. Despite optimal treatments, mortality in the high-risk population of octo- and nonagenarians with PAD remains excessive, and predictive factors need to be identified. The objective of this study was to investigate predictors of mortality in octo- and nonagenarians with PAD.. Cases of treated octo- and nonagenarians, including the clinical characteristics and markers of myocardial injury and heart failure, were studied retrospectively with respect to all-cause mortality. Hazard ratios [HR] were calculated and survival was analyzed by Kaplan-Meyer curves and receiver operating characteristic curved were assessed for troponin-ultra and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and chronic limb-threatening ischemia (CLTI).. A total of 123 octo- and nonagenarians admitted for PAD were eligible. The troponin level was the major predictor of all-cause mortality (HR: 4.6, 95% confidence interval [CI]: 1.4-15.3), followed by the NT-proBNP level (HR: 3.9, 95% CI 1.8-8.8) and CLTI (HR: 3.1, 95% CI 1.6-5.9). Multivariate regression revealed that each increment of 1 standard deviation in log troponin and log NT-proBNP was associated with a 2.7-fold (95% CI 1.8-4.1) and a 1.9-fold (95% CI 1.2-2.9) increased risk of all-cause death. Receiver operating characteristic curve analysis using a combination of all predictors yielded an improved area under the curve of 0.888. In a control group of an equal number of younger individuals, only NT-proBNP (HR: 4.2, 95% CI 1.2-14.1) and CLTI (HR: 6.1, 95% CI 1.6-23.4) were predictive of mortality.. Our study demonstrates that cardiovascular biomarkers and CLTI are the primary predictors of increased mortality in elderly PAD patients. Further risk stratification through biomarkers in this high-risk population of octo- and nonagenarians with PAD is necessary.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Biomarkers; Chronic Disease; Female; Humans; Ischemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Troponin

To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker's clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable.. The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient's entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers.. Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes.. For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.

Topics: Biomarkers; Chronic Disease; Coronary Artery Disease; Glomerular Filtration Rate; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Troponin T

Topics: Acetylglucosaminidase; Aged; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Kaplan-Meier Estimate; Lipocalin-2; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Proportional Hazards Models; Survival Rate; Time Factors

Quantification of hemodynamics and right ventricular (RV) function is crucial for pulmonary hypertension (PH). Cardiovascular magnetic resonance-based heart deformation analysis (CMR-HDA) has been used to assess the ventricular strain.. This study was to determine the correlation of right ventricular longitudinal strain (RVLS) assessed with CMR-HDA with RV function as well as hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH).. Thirty-six CTEPH patients were prospectively included in this research. Each patients underwent CMR and right heart catheterization (RHC). RVLS and RV ejection fraction (RVEF) was quantified from cine images acquired with a retrospectively gated turbo FLASH gradient-echo sequence. The late gadolinium enhancement (LGE) images were acquired using a 2D inversion recovery phase-sensitive fast gradient-echo sequence. Hemodynamics were determined with RHC.. Right ventricular longitudinal strain measured with CMR-HDA was -13.99 ± 4.94%. Bland-Altman plots showed statistical agreement with RVLS with low intra- and interobserver variability. RVLS correlated with serum N-terminal-pro-B-type natriuretic peptide (r = 0.615, P < .001). RVLS inversely correlated with RVEF (r = -0.699, P < .001), and it was positively correlated with both RVESV (r = 0.664, P < .001) and myocardial the volume of LGE (r = 0.447, P = .008). Receiver-operating characteristic (ROC) indicated that RVLS values of >-14.20% could be used to predict RVEF <40% with a 100% sensitivity and a 96.7% specificity. Hemodynamically, RVLS was positively correlated with mean pulmonary artery pressure (r = 0.598, P < .001) and pulmonary vascular resistance (r = 0.685, P < .001).. Right ventricular longitudinal strain assessed by CMR-HDA is a readily available and reproducible parameters of RV function. RVLS >-14.20% suggests the presence of RV dysfunction.

Topics: Adult; Cardiac Catheterization; Chronic Disease; Contrast Media; Echocardiography; Female; Gadolinium; Hemodynamics; Humans; Hypertension, Pulmonary; Image Interpretation, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Peptide Fragments; Pulmonary Embolism; Pulmonary Wedge Pressure; Retrospective Studies; Sensitivity and Specificity; Stroke Volume; Vascular Resistance; Ventricular Dysfunction, Right; Ventricular Function, Right

This prospective study aimed to evaluate the value of the cardiac cycle time-corrected electromechanical activation time (EMATc) measured at admission for predicting major cardiac adverse events (MACEs) in hospitalized patients with chronic heart failure (CHF).. CHF patients with a left ventricular ejection fraction (LVEF) lower than 50% (. Elevated EMATc was an independent risk factor for MACEs (. We demonstrated that an elevated EMATc measured at admission is an independent risk factor for MACEs among hospitalized CHF patients. Acoustic cardiography measured at admission may provide a simple, noninvasive method for risk stratification of CHF patients. This trial is registered with ChiCTR1900021470.

Topics: Action Potentials; Adult; Aged; Biomarkers; Chronic Disease; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Rate; Heart Sounds; Hospitalization; Humans; Inpatients; Male; Middle Aged; Natriuretic Peptide, Brain; Phonocardiography; Point-of-Care Testing; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ventricular Function, Left

Hyperkalemia is one of the most frequent side effects related to renin-angiotensin-aldosterone system (RAAS) inhibition, and can influence optimization of heart failure (HF) therapy.. To evaluate the occurrence of hyperkalemia in a series of outpatients with chronic HF and its relationship with RAAS inhibitor therapy.. We evaluated consecutive outpatients with HF and a reduced left ventricular ejection fraction. The incidence of hyperkalemia and consequent changes in RAAS inhibitor therapy were evaluated for each patient.. A history of hyperkalemia or at least 1 episode of hyperkalemia during follow-up was observed in 104 of 351 patients. Hyperkalemia mainly influenced mineralocorticoid receptor antagonist (MRA) therapy and, among patients with hyperkalemia, not taking MRA was associated with a greater risk of death on univariate analysis (HR = 6.39; 95% CI 2.76-14.79, p < 0.001) and multivariate analysis (HR = 5.24; 95% CI 1.87-14.72, p = 0.002) after correction for age, ischemic cardiomyopathy, diabetes, systolic arterial pressure, New York Heart Association class 3, left ventricular ejection fraction, presence of hyponatremia, glomerular filtration rate calculated by the EPI formula, and presence of N-terminal pro-B-type natriuretic peptide >1,000 pg/mL.. The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis. In this setting, the possibility of managing hyperkalemia using new classes of drugs could allow continuation of MRA therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hyperkalemia; Hyponatremia; Incidence; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Renin-Angiotensin System; Retrospective Studies; Safety-Based Drug Withdrawals; Stroke Volume; Ventricular Dysfunction, Left

Deep vein thrombosis (DVT) is frequently observed in patients with chronic heart failure (CHF), increasing the risk of pulmonary embolism (PE). Clinical evaluation of CHF patients with suspected acute PE is challenging since these diseases share several symptoms and signs such as dyspnea. Thus, it is intuitive that correct and fast diagnosis of PE in these patients might be able to significantly change their clinical outcome. In the present report, we describe a rare case of a patient with CHF and PE due to a huge thrombosis of deep veins and of right atrium in whom echo evaluation permitted the correct diagnosis and therapy.

Topics: Aged; Anticoagulants; Chronic Disease; Echocardiography; Factor Xa Inhibitors; Heart Atria; Heart Failure; Heparin; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Thrombosis; Treatment Outcome; Ultrasonography; Venous Thrombosis

BACKGROUND The aim of this study was to investigate the association between cystatin C and cardiac function and long-term prognosis in patients with chronic heart failure (CHF). MATERIAL AND METHODS We selected 418 CHF patients admitted to our hospital as subjects. Patients were divided into 3 groups according to the cystatin C level (Quantile 1 group: 0.65-1.04 mg/L, Quantile 2 group: 1.05-1.35 mg/L, and Quantile 3 group: 1.36-7.84 mg/L), and patients were followed up for 5 years. We used odds ratio (OR) and 95% confidence interval (CI) to compare the results. RESULTS The cystatin C and NT-ProBNP level in the cardiac function grade (NYHA) class IV group were higher than those in the class III group (P<0.05). Pearson correlation analysis showed that there was a positive correlation between cystatin C and NT-ProBNP log₁₀ transform in CHF patients (r=0.411). During 5-year follow-up, 231 patients died and the 5-year all-cause mortality rate was 55.26% (231/418). There was a significant difference in 5-year all-cause mortality among the 3 groups (P for trend=0.010). After adjusting for potential confounders by multivariate regression analysis, the Quantile 2 group vs. Quantile 1 group were OR=0.83, 95% CI 0.51 to 1.35, P=0.448, and the Quantile 3 group vs. Quantile 1 group were OR=1.71, 95% CI. 1.04 to 2.82, P=0.034. Curve fitting showed that cystatin C was positively correlated with 5-year all-cause mortality in CHF patients. CONCLUSIONS Cystatin C was positively correlated with cardiac function and NT-ProBNP in CHF patients. Cystatin C could be used as a serological index to evaluate the long-term prognosis of CHF patients.

Topics: Adolescent; Adult; Aged; Biomarkers; Chronic Disease; Cystatin C; Disease Progression; Female; Follow-Up Studies; Heart; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Young Adult

Chronic peripheral oedema is frequent in old patients, and very often results from multiple causes.. To investigate whether determination of B-type natriuretic peptide plasma concentration helps with the diagnosis of chronic peripheral oedema aetiologies.. This was a cross-sectional observational study conducted in geriatric hospital wards (intermediate and long-term care) on consecutive in-hospital patients aged>75 years with chronic peripheral oedema and no dyspnoea. From medical history, physical examination, routine biological tests and chest radiography, two investigators determined the aetiologies of oedema, with special attention paid to recognizing chronic heart failure. This reference diagnosis was compared with the clinical diagnosis mentioned in the medical chart. Brain natriuretic peptide plasma concentrations were measured soon after the investigators' visit.. Among the 141 patients (113 women and 28 men) aged 86±6 years, a single aetiology was identified in 53 (38%), and multiple aetiologies in 84 (60%). The main aetiologies were venous insufficiency (69%), chronic heart failure (43%), hypoproteinaemia (38%) and drug-induced oedema (26%). Chronic heart failure was frequently misdiagnosed by attending clinicians (missed in 18 cases and wrongly diagnosed in 14 cases). Brain natriuretic peptide concentration was significantly higher in patients with chronic heart failure than in those without: median (interquartile range) 490 (324-954) versus 137 (79-203) pg/mL, respectively (P<0.0001). The receiver operating characteristic curve showed that a concentration of 274pg/mL was appropriate for diagnosing chronic heart failure, with a specificity of 0.89 and a sensitivity of 0.82. Brain natriuretic peptide concentrations above this cut-off were significantly and independently associated with the diagnosis of chronic heart failure.. Chronic heart failure is frequently misdiagnosed in old patients with chronic peripheral oedema, and B-type natriuretic peptide plasma concentration helped to improve the diagnosis of this condition and identify chronic heart failure.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cross-Sectional Studies; Edema; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors

Objective Investigate the role of biomarkers in the prognosis of the clinical course of the disease in patients with chronic heart failure (CHF) of different NYHA functional classes (FC).Material and Methods The study included 132 patients with CHF: Group 1 was composed of 70 patients with NYHA FC II CHF, and Group 2 included 62 patients with FC III-IV CHF. The patients underwent clinical, instrumental, functional, and laboratory measurements, which included serum concentrations of NT-proBNP, ST-2, galectin-3, and C-reactive protein. Patients were examined at baseline and at 3, 6, and 12 mos of follow-up. The following cardiac complications were used as endpoints: urgent hospitalization due to decompensated CHF, heart transplantation, cardiovascular death. Endpoints were registered during the 12-mo follow-up period.Results Endpoints were recorded for 58 patients (44%) of the total sample of patients with CHF: 38 patients were urgently hospitalized, 10 patients underwent heart transplantation, 10 patients died. Cardiac complications were recorded at a higher rate in patients with FC III-IV CHF (63% vs. 27% of patients with FC II; p<0.001). In FC II CHF patients, the incidence of cardiac complications was significantly correlated with NT-proBNP blood concentrations (Rpb=0.53; p=0.023), left ventricular end-diastolic volume (LVEDV) (Rpb=0.50; p=0.044), and mitral regurgitation (Rpb=0.53; p=0.038). Cardiac complications in patients with FC III-IV CHF were associated with ST-2 (Rpb=0.52; p=0.004) and galectin-3 (Rpb=0.46; p=0.009) blood concentrations, and with systolic pulmonary artery pressure (PAP) (Rpb=0.41; p=0.014). Unlike other laboratory measurements, galectin-3 concentrations were significantly correlated with type 2 diabetes mellitus (DM2) (Rpb=0.40; p=0.003). In this study, correlation analysis and evidence of significant differences in the concentrations of biomarkers provided a rationale for identifying potential predictors of severe cardiac complications during medium- and long-term follow-up periods in patients with CHF of different severity: NT-proBNP concentrations in FC II patients; ST-2 and galectin-3 serum concentrations in FC III-IV patients; galectin-3 concentrations in patients with CHF and DM2.Conclusion NT-proBNP blood concentrations are associated with CHF severity and serious cardiac complications in patients with FC II CHF within the following 12 mos. The poor prognosis of FC III-IV CHF is associated with the concentration of the

Topics: Biomarkers; Chronic Disease; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Cardiac damage triggered by severe hypocalcemia is well known. However, the role of chronic hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP) in cardiac health is still unclear. We investigated the effect of chronic HP and PHP on cardiac structure and conductive function in patients compiling with treatment.. The study included 18 patients with HP and eight with PHP aged 45.4 ± 15.4 and 22.1 ± 6.4 years, respectively with a previously regular follow-up. In addition, 26 age- and sex-matched healthy controls were included. General characteristics and biochemical indices were recorded. Cardiac function and structure were assessed by estimation of myocardial enzymes, B-type natriuretic peptide (BNP), and echocardiography. The 12-lead electrocardiogram and 24-h Holter electrocardiography were performed to evaluate the conductive function.. Levels of serum calcium in HP and PHP were 2.05 ± 0.16 mmol/L and 2.25 ± 0.19 mmol/L, respectively. The levels of myocardial enzyme and BNP were within the normal range. Adjusting for age at evaluation and body mass index, all M-mode measurements, left ventricular mass (LVM), LVM index (LVMI) and relative wall thickness (RWT) were comparable between patients and controls. Prolongation of corrected QT (QTc) intervals occurred in 52.6% (10/19) of patients, and 6.7% (1/15) of patients manifested more than 100 episodes of supraventricular and ventricular extrasystoles, as well as supraventricular tachycardia. None of the above arrhythmias was related to a severe clinical event.. From this pilot study, patients diagnosed with HP and PHP and well-controlled serum calcium levels manifested normal cardiac morphology and ventricular function, except for prolonged QTc intervals, and a small percentage of mild arrhythmias needing further investigation.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Atrial Premature Complexes; Calcium; Case-Control Studies; Chronic Disease; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Female; Humans; Hypoparathyroidism; Long QT Syndrome; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Pseudohypoparathyroidism; Tachycardia, Supraventricular; Ventricular Dysfunction, Left; Ventricular Premature Complexes; Young Adult

Background Neprilysin is a transmembrane endopeptidase involved in the breakdown of a variety of vasoactive peptides and serves as a therapeutic target in heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the relationship of circulating neprilysin with neurohumoral activation and the impact of plasma neprilysin activity on prognosis in HFrEF. Methods and Results A total of 369 chronic HFrEF patients were enrolled prospectively. Plasma neprilysin concentration and activity were determined by a specific ELISA and a fluorometric method. The association between plasma neprilysin and heart failure (HF) severity, neurohumoral activation, ie norepinephrine and absolute renin concentration, as well as all-cause mortality was assessed. Median plasma neprilysin concentrations and activity levels were 413 pg/mL (interquartile range 0-4111) and 2.36 nmol/mL per minute (interquartile range 1.16-4.59). No correlation could be shown between plasma neprilysin concentrations and activity (

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Neurotransmitter Agents; Norepinephrine; Peptide Fragments; Prognosis; Prospective Studies; Registries; Renin; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potential biomarker for monitoring the status of heart failure. However, the optimal monitoring interval of NT-proBNP is unknown. This study sought to investigate the minimal informative monitoring interval of NT-proBNP in patients with stable chronic heart failure.. This retrospective cohort study included patients who were admitted due to heart failure and subsequently followed with serial NT-proBNP measurements in a tertiary hospital. We analyzed NT-proBNP measured between six months after discharge and the earliest timepoint of: an alteration of medication regimen, readmission due to worsening of heart failure, or all-cause death. To distinguish progression of the disease from biological variability and measurement error, the signal-to-noise ratio method was applied with a random-effects model.. In the 368 patients included, NT-proBNP was measured for a median 6 times. In the random-effects model, signal (progression of disease) exceeded noise (biological variability and measurement error) at 7.9 months (95% confidence interval [CI]: 5.1-9.6), while noise corresponded to a 61% increase from baseline. In stratified analysis using the AHEAD risk score, the minimal informative monitoring interval shortened as the risk score increased (0-1 point: 12.2 months [95%CI: 10.3-14.4]; 2-3 points: 8.0 months [95%CI: 6.8-9.7]; 4-5 points: 3.3 months [95%CI: 3.0-3.8]).. In patients with stable chronic heart failure, the minimal informative monitoring interval of NT-proBNP measurement was 7.9 months in the current population, which varied with underlying risks. The optimal monitoring interval could be lengthened for patients at lower risks.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Disease Progression; Female; Heart Disease Risk Factors; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reproducibility of Results; Retrospective Studies; Risk Assessment; Time Factors

Aim To study the interrelationship between intensity of chronic systemic inflammation (CSI) with severity of the condition and intestinal microbiocenosis parameters in patients with chronic heart failure (CHF).Material and methods 47 hospitalized patients with symptomatic CHF were evaluated. The following parameters were determined: clinical condition; N-terminal pro-B-type natriuretic peptide (NT-proBNP). C-reactive protein (CRP); serum interleukins (IL) 6 and 10; and intestinal microbiocenosis composition by mass-spectrometry of microbial markers in whole blood. Microbiocenosis indexes were compared in the main group and in 38 outpatient patients with arterial hypertension and ischemic heart disease without CHF.Results Direct, medium-power correlations were found between CRP and IL-6 concentrations and severity of clinical condition (NT-proBNP, ХСН stage, and edema severity) in patients with CHF. Most patients with CHF had lower numbers of bifido-, lacto-, propionic-, and eubacteria, and Clostridium (С.) ramosum and higher numbers of aspergillus. Among CHF patients, the highest indexes of endotoxemia, gram (-) bacteria, cocci, actinomycetes, and microfungi were observed in the group with NT-proBNP from 400 to 2000 pg/ml. Direct correlations were observed for amounts of C. hystolyticum, Pseudonocardia spp., and Aspergillus spp. with IL-6 and IL-10 and unidirectional inverse correlation were observed for these cytokines with Propionibacterium acnes and jensenii, Streptomyces spp., and Nocardia asteroides. In addition, IL-6 concentration was negatively correlated with contents of Staphylococcus aureus, C. difficile, C. ramosum, Eggerthella lenta, and Corynebacterium spp. and was positively correlated with C. propionicum, Moraxella spp. and Flavobacterium spp. Concentration of IL-6 directly correlated with the number of Eubacterium spp. and inversely correlated with numbers of Ruminicoccus spp. and Streptomyces farmamarensis. The amount of Streptomyces farmamarensis negatively correlated with CRP concentrations.Conclusion The study results evidence the significance of intestinal microbial-tissue complex in the pathogenesis of CSI in CHF and allow suggesting this complex as a promising target for therapy.

Topics: Biomarkers; Chronic Disease; Clostridioides difficile; Gastrointestinal Microbiome; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments

We did a comparative analysis of matched and mismatched defects in pre- and post-operative V/Q scans in CTEPH patients. We correlated the number of these defects with pre-operative clinical and hemodynamic parameters.. This was a retrospective study on 27 patients with CTEPH who underwent surgery. Pre- and post-operative V/Q scans were graded for each lung segment as normal, matched or mismatched defect. Additional pre- and post-operative clinical and hemodynamic parameters that were collected include New York Heart Association functional class, six-minute walk distance in feet, N-terminal pro b-type natriuretic peptide, forced expiratory volume in one second/forced vital capacity, diffusing capacity of the lung for carbon monoxide, pulmonary arterial pressure (systolic, diastolic and mean), right atrial pressure, cardiac output and cardiac index. Pulmonary vascular resistance was then calculated.. On a segmental basis, 176 mismatched defects were noted in 27 patients, of which 111 improved post-surgery (63%). 22 of the 34 matched defects improved following surgery (64%). 31 new mismatched defects were observed. The number of pre-operative matched defects per patient ranged from 0 to 6. No statistically significant associations were observed between the number of pre-operative matched defects and pre-operative clinical parameters. No statistically significant associations were observed between the number of improved matched defects and the change in clinical parameters (pre- to post-surgery).. Both matched and mismatched defects on preoperative V/Q scans can show normalization post-surgery. The extent of matched defects on a preoperative V/Q scan does not correlate significantly with other clinical and hemodynamic parameters.

Topics: Chronic Disease; Female; Humans; Hypertension, Pulmonary; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Retrospective Studies; Ventilation-Perfusion Scan

The association among psychological, neuropsychological dysfunctions and functional/clinical variables in Chronic Heart Failure (CHF) has been extensively addressed in literature. However, only a few studies investigated those associations in the older population.. To evaluate the psychological/neuropsychological profile of older CHF patients, to explore the interrelation with clinical/functional variables and to identify potential independent predictors of patients' functional status.. This study was conducted with a multi-center observational design. The following assessments were performed: anxiety (Hospital Anxiety and Depression Scale, HADS), depression (Geriatric Depression Scale, GDS), cognitive impairment (Addenbrooke's Cognitive Examination Revised, ACE-R), executive functions (Frontal Assessment Battery, FAB), constructive abilities (Clock Drawing Test, CDT), psychomotor speed and alternated attention (Trail Making Test, TMT-A/B), functional status (6-minute walking test, 6MWT) and clinical variables (New York Heart Association, NYHA; Brain Natriuretic Peptide, BNP; left ventricular ejection fraction, LVEF; left ventricular end diastolic diameter, LVEDD; left ventricular end diastolic volume, LVEDV; tricuspid annular plane systolic excursion, TAPSE).. 100 CHF patients (mean age: 74.9±7.1 years; mean LVEF: 36.1±13.4) were included in the study. Anxious and depressive symptoms were observed in 16% and 24,5% of patients, respectively. Age was related to TMT-A and CDT (r = 0.49, p<0.001 and r = -0.32, p = 0.001, respectively), Log-BNP was related to ACE-R-Fluency subtest, (r = -0.22, p = 0.034), and 6MWT was related to ACE-R-Memory subtest and TMT-A (r = 0.24, p = 0.031 and r = -0.32, p = 0.005, respectively). Both anxiety and depression symptoms were related to ACE-R-Total score (r = -0.25, p = 0.013 and r = -0.32, p = 0.002, respectively) and depressive symptoms were related to CDT (r = -0.23, p = 0.024). At multiple regression analysis, Log-BNP and TMT-A were significant and independent predictors of functional status: worse findings on Log-BNP and TMT-A were associated with shorter distance walked at the 6MWT.. Psychological and neuropsychological screening, along with the assessment of psychomotor speed (TMT-A), may provide useful information for older CHF patients undergoing cardiac rehabilitation.

Topics: Aged; Aged, 80 and over; Anxiety; Cardiac Rehabilitation; Chronic Disease; Cross-Sectional Studies; Depressive Disorder; Emotions; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Regression Analysis; Stroke Volume; Trail Making Test; Ventricular Function, Left; Walk Test

Data on the impact of COVID-19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID-19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline-directed medical therapy (GDMT) and worse outcomes during hospitalization.. Data for a total of 3080 consecutive patients with confirmed COVID-19 infection and follow-up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N-terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in-hospital mortality.. Patients with COVID-19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID-19 diagnosis. The withdrawal of GDMT was associated with higher mortality.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Chronic Disease; COVID-19; Deprescriptions; Disease Progression; Female; Heart Failure; Hospital Mortality; Humans; Incidence; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Risk Factors; SARS-CoV-2; Spain

During the COVID-19 pandemic, non-urgent outpatient activities were temporarily suspended. The aim of this study was to assess the impact of this measure on the management of the heart failure outpatient clinic at our institution.. We analyzed the clinical outcome of 110 chronic heart failure patients (mean age 73 ± 9 years) whose follow-up visit had been delayed.. At their last visit before the lockdown, 80.9% was in NYHA class II, had an ejection fraction of 37 ± 7%, and B-type natriuretic peptide level was moderately elevated (266 ± 138 pg/ml). All patients received loop diuretics, 97.2% beta-blockers, 64.9% an aldosterone antagonist, 60.9% sacubitril/valsartan (S/V), and 72.2% of the remaining patients were on angiotensin-converting enzyme inhibitor or valsartan therapy. Patients were contacted by phone during and at the end of the lockdown period to fix a new appointment and underwent a structured interview to assess their clinical conditions and ongoing therapy and to verify whether they had contracted SARS-CoV-2 infection. Twelve patients (13.2%) contracted COVID-19. None was hospitalized for worsening heart failure or reported defibrillator shocks and none changed autonomously the prescribed therapy. Overall, 75% of patients reported stable or improved general well-being from the last in-person visit, while 25% described subjective worsening due to the social effect of the pandemic. Unchanged body weight and blood pressure values were reported by 86% and 78.4% of patients, respectively. Lower blood pressure values compared to baseline were recorded in 15.2% of patients on conventional renin-angiotensin system inhibition vs 21% of those on S/V, one of whom had to down-titrate S/V for persistent but asymptomatic hypotension; 4 patients up-titrated S/V to 200 mg/day following phone indications.. Cancellation of scheduled follow-up visits during 3 months did not have significant negative effects in a cohort of stable patients with chronic heart failure on optimized medical therapy. Telephone support was effective in keeping connections with the patients during the lockdown, allowing appropriate management and implementation of drug therapy. In particular, patients who received S/V were not affected by delays in scheduled visits, confirming the tolerability and safety of this novel therapy in terms of both clinical and biohumoral parameters.

Topics: Adrenergic beta-Antagonists; Aged; Ambulatory Care Facilities; Aminobutyrates; Angiotensin-Converting Enzyme Inhibitors; Betacoronavirus; Biphenyl Compounds; Chronic Disease; Continuity of Patient Care; Coronavirus Infections; COVID-19; Delivery of Health Care; Disease Progression; Drug Combinations; Female; Heart Failure; Humans; Italy; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Pandemics; Pneumonia, Viral; Quarantine; Recurrence; SARS-CoV-2; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Telephone; Tetrazoles; Valsartan; Withholding Treatment

BACKGROUND Chinese hawthorn (Crataegus pinnatifida) fruit is a traditional Chinese medicine for treatment of digestive system and cardiovascular diseases. The fruit contains polyphenol compounds, such as epicatechin, that have anti-inflammatory activity. This study aimed to investigate the effects of an alcohol extract of hawthorn fruit (HAE) on inflammation and oxidative stress in rats with doxorubicin-induced chronic heart failure (CHF). MATERIAL AND METHODS Rats were intraperitoneally injected with doxorubicin to induce CHF and subsequently treated with HAE intragastrically once daily for 6 weeks. At the end of the experiment, echocardiographic and hemodynamic parameters were assessed, and enzyme-linked immunoassays were used to detect the levels of cardiac injury markers (brain natriuretic peptide, creatine kinase-MB, aspartate aminotransferase, lactate dehydrogenase, copeptin, and adrenomedullin), oxidative stress markers (glutathione peroxidase and malondialdehyde), and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-1ß, and tumor necrosis factor-a). The IL-1ß, IL-6, glutathione peroxidase-1, and catalase mRNA levels were also measured by quantitative real-time polymerase chain reaction. RESULTS Our findings indicated that HAE exerts a cardioprotective effect, as shown by improved echocardiographic and hemodynamic parameters, decreased activity of serum myocardial enzymes, reduced serum levels of CHF markers, and inhibited inflammatory response in cardiac tissue. In addition, HAE treatment downregulated the mRNA expression of IL-1ß and tumor necrosis factor-alpha and upregulated the mRNA expression of glutathione peroxidase-1 and catalase compared with untreated doxorubicin-induced CHF rats. CONCLUSIONS HAE shows promise for the prevention and treatment of CHF. The cardioprotective effect of HAE appears to be related to inhibition of both the inflammatory response and oxidative stress in vivo.

Topics: Adrenomedullin; Animals; Antioxidants; Aspartate Aminotransferases; Chromatography, High Pressure Liquid; Chronic Disease; Crataegus; Creatine Kinase; Cytokines; Doxorubicin; Electrocardiography; Ethanol; Fruit; Glutathione Peroxidase; Glycopeptides; Heart Failure; Heart Function Tests; Inflammation; L-Lactate Dehydrogenase; Male; Malondialdehyde; Natriuretic Peptide, Brain; Oxidative Stress; Plant Extracts; Polyphenols; Rats, Wistar; RNA, Messenger

to evaluate the effectiveness of cardiac contractility modulation (MSS) in patients with chronic heart failure (CHF) and atrial fibrillation (AF).. The following studies were performed in 40 patients with CHF and AF before implantation of the MSS device and after 2 and 6 months of follow-up: 12-channel ECG, transthoracic EchoCG, 6-minute walk test, determination of the level of Pro-natriuretic N-terminal peptide (NT-proBNP), daily ECG monitoring, and a questionnaire based on the Minnesota quality of life questionnaire for patients with CHF (MHFLQ). All patients received long-term optimal drug therapy for CHF before surgery.. The results obtained indicate a statistically significant positive effect of the use of MSS in patients with CHF and AF on LV FV, the functional class of CHF, and levels of NT-proBNP regardless of the etiology of CHF.. The use of MSS may be promising for the treatment of heart failure in patients with CHF and AF.. Цель.Оценить эффективность модуляции сердечной сократимости (МСС) у пациентов с хронической сердечной недостаточностью (ХСН) и фибрилляцией предсердий (ФП). Материалы и методы.У 40 пациентов с ХСН и ФП до имплантации устройства МСС и через 2 и 6 мес наблюдения проводились следующие исследования: 12-канальная электрокардиограмма (ЭКГ), трансторакальная эхокардиография, тест 6-минутной ходьбы, определение уровня про-натрийуретического N-концевого пептида (NT-proBNP), суточное мониторирование ЭКГ, анкетирование по Миннесотскому опроснику качества жизни больных с ХСН (MHFLQ). Все пациенты до операции получали длительную оптимальную медикаментозную терапию ХСН. Результаты.Полученные результаты свидетельствуют о статистически значимом положительном влиянии применения МСС у пациентов с ХСН и ФП на фракцию выброса левого желудочка, функциональный класс ХСН, а также уровни NT-proBNP независимо от этиологии ХСН. Заключение.Применение МСС может являться перспективным в плане лечения сердечной недостаточности у пациентов с ХСН и ФП.

Topics: Atrial Fibrillation; Chronic Disease; Electrocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life

Plasma concentrations of high-sensitivity C-reactive protein (hsCRP) are often raised in chronic heart failure (CHF) and might indicate inflammatory processes that could be a therapeutic target. We aimed to study the associations between hsCRP, mode and cause of death in patients with CHF.. We enrolled 4423 patients referred to a heart failure clinic serving a local population. CHF was defined as relevant symptoms or signs with either a reduced left ventricular ejection fraction <40% or raised plasma concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP >125 pg/mL). The median [interquartile range (IQR)] plasma hsCRP for patients diagnosed with CHF (n = 3756) was 3.9 (1.6-8.5) mg/L and 2.7 (1.3-5.1) mg/L for those who were not (n = 667; P < 0.001). Patients with hsCRP ≥10 mg/L (N = 809; 22%) were older and more congested than those with hsCRP <2 mg/L (N = 1117, 30%). During a median follow-up of 53 (IQR 28-93) months, 1784 (48%) patients with CHF died. Higher plasma hsCRP was associated with greater mortality, independent of age, symptom severity, creatinine, and NT-proBNP. Comparing a hsCRP ≥10 mg/L to <2 mg/L, the hazard ratio for all-cause mortality was 2.49 (95% confidence interval 2.19-2.84; P < 0.001), for cardiovascular (CV) mortality was 2.26 (1.91-2.68; P < 0.001), and for non-CV mortality was 2.96 (2.40-3.65; P < 0.001).. In patients with CHF, a raised plasma hsCRP is associated with more congestion and a worse prognosis. The proportion of deaths that are non-CV also increases with higher hsCRP.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cause of Death; Chronic Disease; Female; Heart Failure; Humans; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prognosis; Risk Assessment; Risk Factors; Stroke Volume; Up-Regulation; Ventricular Function, Left

Cardiac cachexia is a wasting syndrome characterized by chronic inflammation and high mortality. Fibroblast growth factor 21 (FGF-21) and monocyte chemoattractant protein 1 (MCP-1) are associated with cardiovascular disease and systemic inflammation. We investigated FGF-21 and MCP-1 in relations to cardiac function, inflammation, and wasting in patients with heart failure with reduced ejection fraction (HFrEF) and cardiac cachexia.. Plasma FGF-21 and MCP-1 were measured in a cross-sectional study among the three study groups: 19 patients with HFrEF with cardiac cachexia, 19 patients with HFrEF without cachexia, and 19 patients with ischaemic heart disease and preserved ejection fraction. Patients with HFrEF and cardiac cachexia displayed higher FGF-21 levels median (inter quantile range) 381 (232-577) pg/mL than patients with HFrEF without cachexia 224 (179-309) pg/mL and ischaemic heart disease patients 221 (156-308) pg/mL (P = 0.0496). No difference in MCP-1 levels were found among the groups (P = 0.345). In a multivariable regression analysis, FGF-21 (logarithm 2) was independently associated with interleukin 6 (logarithm 2) (P = 0.015) and lower muscle mass (P = 0.043), while no relation with N-terminal pro-hormone brain natriuretic peptide was observed.. Fibroblast growth factor 21 (FGF-21) levels were elevated in patients with HFrEF and cardiac cachexia, which could be mediated by increased inflammation and muscle wasting rather than impaired cardiac function.

Topics: Aged; Aged, 80 and over; Biomarkers; Cachexia; Cardiovascular Diseases; Case-Control Studies; Chemokine CCL2; Chronic Disease; Cross-Sectional Studies; Denmark; Female; Fibroblast Growth Factors; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Muscular Atrophy; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Wasting Syndrome

An increased cardiac troponin T (cTnT) level identifies a high-risk group in patients with end-stage renal disease; however, the mechanism of cTnT elevation remains unclear in such patients without acute coronary syndrome (ACS). Therefore, we explored the relationship between cTnT levels and the hemodynamic parameters and the prognostic potential of cTnT in stable patients with chronic hemodialysis (HD).. We included consecutive 174 patients with HD who were referred for coronary angiography due to stable coronary artery disease (CAD), peripheral artery disease (PAD), or heart failure (HF). Hemodynamic measurement was performed, and plasma cTnT, B-type natriuretic peptide (BNP), and A-type natriuretic peptide (ANP) were measured at the same time. The potential of 3 biomarkers to predict all-cause mortality, cardiac death or hospitalized HF, and vascular event was assessed.. Increased log cTnT levels were correlated with increased log BNP and log ANP levels (r = 0.531, p < 0.001 and r = 0.411, p < 0.001, respectively). Not increased log cTnT, but increased log BNP and log ANP were associated with the presence of CAD and the extent of CAD. In contrast, they were all associated with the New York Heart Association functional classification and the presence of PAD and significantly correlated with left ventricular end-diastolic pressure (LVEDP) in an independent manner. Increased cTnT and BNP levels were associated with the mortality and hospitalized HF. However, increased cTnT was not associated with vascular events, unlike increased BNP.. In patients with chronic HD without ACS, increased cTnT reflected increased LVEDP and the presence of HF or PAD independently, and it did not reflect the presence of CAD in contrast to increased BNP. cTnT and BNP were significant prognostic predictors; however, increased cTnT was associated with HF-related events, not with arteriosclerotic events.

Topics: Aged; Cardiovascular Diseases; Chronic Disease; Female; Humans; Male; Natriuretic Peptide, Brain; Renal Dialysis; Troponin T

Research comparing bosentan and macitentan in chronic thromboembolic pulmonary hypertension (CTEPH) is scarce, although macitentan might have superior pharmacologic properties. We present the first real-world, 2-year follow-up results and compare clinical outcomes of both drugs in CTEPH.. All consecutive, technical inoperable or residual CTEPH patients receiving bosentan or macitentan, diagnosed in our multidisciplinary team between January 2003 and January 2019, were included. We report and compare survival, clinical worsening (CW), adverse events, WHO FC, NT-proBNP and 6-min walking test (6MWT) until 2 years after medication initiation.. In total, 112 patients receiving bosentan or macitentan (58% female, mean age 62 ± 14 years, 68% WHO FC III/IV, 51% bosentan) could be included. Mean treatment duration was 1.9 ± 0.4 years for bosentan and 1.2 ± 0.6 years for macitentan. Two-year survival rate was 91% for bosentan and 80% for macitentan (HR mortality macitentan 1.85 [0.56-6.10], p = 0.31). Two-year CW-free survival was 81% and 58%, respectively (HR CW macitentan 2.16 [0.962-4.87], p = 0.06). Right atrial pressure, cardiac output (for mortality alone) and 6MWT lowest saturation were multivariate predictors at baseline. Overall adverse event rates were comparable and WHO FC, NT-proBNP and 6MWT distance improved similar for both drugs till 2-year follow-up.. CTEPH patients receiving bosentan or macitentan have improved clinical outcomes till 2-year follow-up, without significant differences in outcomes between both therapies.

Topics: Aged; Bosentan; Chronic Disease; Drug Therapy, Combination; Endarterectomy; Endothelin Receptor Antagonists; Enzyme Activators; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Pulmonary Embolism; Pyrazoles; Pyrimidines; Retrospective Studies; Sildenafil Citrate; Sulfonamides; Survival Rate; Walk Test

Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Chronic Disease; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Mitochondria; Natriuretic Peptide, Brain; Oxygen Consumption; Reactive Oxygen Species; Severity of Illness Index

Balloon pulmonary angioplasty (BPA) has been demonstrated to improve cardiac function and exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its instant impact on cardiopulmonary function has seldom been evaluated. This study aims to determine the safety and efficacy of BPA and its immediate and lasting effects on cardiopulmonary function among CTEPH patients.. From May 2018 to January 2019, patients with inoperable CTEPH who underwent BPA sessions were consecutively enrolled. Hemodynamics were measured by right heart catheterization, selective pulmonary angiography and BPA were successively conducted. Hemodynamic variables, WHO functional class (WHO-FC), 6-min walk distance (6MWD) and serum NT-proBNP were evaluated before and after BPA sessions during hospitalization. Pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET) were performed within 1-3 days pre and post BPA to evaluate the effect of BPA on cardiopulmonary function.. Twenty-five patients with inoperable CTEPH who underwent a total of forty BPA sessions were consecutively enrolled. A total of 183 segmental or subsegmental vessels (4.6 ± 1.9 vessels per session) in 137 segments (3.4 ± 1.6 segments per session) were dilated. No procedure-related complications occurred. Instant hemodynamics, WHO-FC, 6MWD and NT-proBNP were all significantly improved after a single BPA session. Significant improvement in cardiopulmonary function was also evident as assessed by PFT indexes (forced vital capacity, forced expiratory volume in the first second, maximal voluntary ventilation) and CPET parameters (peak work rate, peak VO. BPA, a safe and effective approach, can bring instant improvements after a single session and lasting benefits after multiple sessions to hemodynamics and cardiopulmonary function for patients with inoperable CTEPH.

Topics: Aged; Angioplasty, Balloon; Biomarkers; Chronic Disease; Exercise Tolerance; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension; Pulmonary Artery; Pulmonary Circulation; Pulmonary Embolism; Recovery of Function; Time Factors; Treatment Outcome

Heart failure (HF) is a major public health problem with increasing prevalence worldwide. It is associated with high mortality and poor quality of life due to recurrent and costly hospital admissions. Several studies have been conducted to describe HF risk predictors in different races, countries and health systems. Nonetheless, understanding population-specific determinants of HF outcomes remains a great challenge. We aim to evaluate predictors of 1-year survival of individuals with systolic heart failure from the GENIUS-HF cohort.. We enrolled 700 consecutive patients with systolic heart failure from the SPA outpatient clinic of the Heart Institute, a tertiary health-center in Sao Paulo, Brazil. Inclusion criteria were age between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤50% in the previous 2 years of enrollment on the cohort. We recorded baseline demographic and clinical characteristics and followed-up patients at 6 months intervals by telephone interview. Study data were collected and data quality assurance by the Research Electronic Data Capture tools. Time to death was studied using Cox proportional hazards models adjusted for demographic, clinical and socioeconomic variables and medication use.. We screened 2314 consecutive patients for eligibility and enrolled 700 participants. The overall mortality was 6.8% (47 patients); the composite outcome of death and hospitalization was 17.7% (123 patients) and 1% (7 patients) have been submitted to heart transplantation after one year of enrollment. After multivariate adjustment, baseline values of blood urea nitrogen (HR 1.017; CI 95% 1.008-1.027; p < 0.001), brain natriuretic peptide (HR 1.695; CI 95% 1.347-2.134; p < 0.001) and systolic blood pressure (HR 0.982;CI 95% 0.969-0.995; p = 0.008) were independently associated with death within 1 year. Kaplan Meier curves showed that ischemic patients have worse survival free of death and hospitalization compared to other etiologies.. High levels of BUN and BNP and low systolic blood pressure were independent predictors of one-year overall mortality in our sample.. Current Controlled Trials NTC02043431, retrospectively registered at in January 23, 2014.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Blood Urea Nitrogen; Brazil; Chronic Disease; Disease Progression; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ventricular Function, Left; Young Adult

To investigate the effect of Qiangxin Huoli decoction on rats with chronic heart failure (CHF) induced by adriamycin (ADR), and to investigate the underlying mechanism of this effect.. Ninety-six healthy Wistar rats were divided into six groups: control, CHF model, CHF treated by Shenfu injection, and three CHF groups treated with Qiangxin Huoli decoction at high, medium, and low doses, respectively. Qiangxin Huoli decoction was administered orally to protect the stomach in the three Qiangxin Huoli decoction groups, while the control group and the CHF model group were administered the same volume of 0.9% physiological saline, and the Shenfu group wereadministered the same volume of Shenfu injection. Ten days later, the CHF model was then induced in all groups except the control group by intraperitoneal injection of ADR at gradient dose intervals. The bodyweights were recorded on days 10, 20, 30, and 40. Hemodynamic indices were recorded, including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum increase in left ventricular pressure (+dp/dtmax), maximum decrease in left ventricular pressure (-dp/dtmax), heart rate (HR), and electrocardiogram using an eight-channel physiological recorder with LabChart software monitoring. The plasma brain natriuretic peptide (BNP) concentration was determined by enzyme-linked immunosorbent adsorption. The expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by immunohistochemical methods.. The CHF model group were in poor condition, and the mean bodyweight was significantly decreased compared with the control group. Furthermore, compared with the control group, the CHF groups had significantly decreased LVSP, +dp/dtmax, and -dp/dtmax, and significantly increased LVEDP. The CHF groups also showed significant increases in HR, S-T segment elevation, and plasma BNP levels compared with the control group. Compared with the CHF model group, the treatment groups had significantly increased Bax expression (P < 0.05) and significantly decreased Bcl-2 expression (P < 0.01), indicating less apoptosis. The high dose Qiangxin Huoli decoction group and the Shenfu group showed the most significant improvements.. In the rat model of CHF, Qiangxin Huoli decoction significantly reduces the abnormal hemodynamics, improves cardiac function, reduces plasma BNP concentration, regulates the expression of apoptosis proteins, inhibits the apoptosis of myocardial cells, and plays a protective role.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Chronic Disease; Drugs, Chinese Herbal; Electrocardiography; Heart Failure; Hemodynamics; Immunohistochemistry; Myocardium; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar

Cardiac performance depends on optimum ventriculoarterial coupling which is impaired in patients with heart failure (HF). Galectin-3 is a mediator of myocardial fibrosis and remodeling, and is associated with clinical status in patients with chronic HF. We examined the association of arterial stiffness with galectin-3 levels in patients with HF of ischemic etiology.. We consecutively enrolled 40 patients with stable ischemic HF and reduced ejection fraction. Central aortic stiffness was evaluated non-invasively by measuring carotid femoral pulse wave velocity (PWV). Among other factors, serum levels of galectin-3 and b-type natriuretic peptide (BNP) were measured.. The median galectin-3 levels in our study population were 12.9 (10.8-18.7) ng/ml and the mean PWV was 9.31±2.79 m/sec. There was significant association of galectin-3 levels with age (r=0.48, p=0.003), creatinine clearance (r=-0.66, p<0.001) and BNP levels (r=0.36, p=0.05). There was a significant association of galectin-3 levels with PWV (r=0.37, p=0.03) and patients with PWV above median also had significantly increased levels of galectin-3 compared with patients with lower values of PWV [16.1(11.8-25.2) vs. 12.1(10.5-14) ng/ml, p=0.03].. We found an association of arterial stiffness and PWV with galectin-3 levels in patients with chronic HF of ischemic etiology. These findings suggest a pathway driving arterial stiffening and myocardial remodelling in HF. This may provide insight into the mechanism determining prognosis and clinical status of patients with HF.

Topics: Aged; Biomarkers; Blood Proteins; Chronic Disease; Female; Galectin 3; Galectins; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Pulse Wave Analysis; Up-Regulation; Vascular Stiffness

To investigate risk factors for perioperative death in elderly patients with intertrochanteric fracture.. Clinical data from 1051 cases with intertrochanteric fracture from March 2005 to March 2015 were reviewed and analyzed, and causes of death during the perioperative period were statistically analyzed. Various indicators were compared by t test and χ. Chronic diseases of major organs (heart, brain, and lung), postoperative complications, and various indicators within 24 h after admission (albumin, hemoglobin, brain natriuretic peptide [BNP], glucose, creatinine, arterial blood pH, PaO. BNP and APACHE II score could be used as important reference indexes for predicting possible perioperative mortality in elderly patients with intertrochanteric fracture and chronic diseases of major organs. Complications after fracture may be also risk factors.

Topics: Aged; Aged, 80 and over; APACHE; Cause of Death; China; Chronic Disease; Female; Hip Fractures; Humans; Male; Natriuretic Peptide, Brain; Perioperative Period; Retrospective Studies; Risk Factors

The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardiology (ESC) guidelines advise natriuretic peptide (NP) assessment in patients presenting to primary care with symptoms possibly due to chronic heart failure (HF), to determine need for specialist involvement. This prospective service evaluation aimed to describe the diagnostic and prognostic utility of these guidelines.. We prospectively collected clinical, echocardiography and outcomes data (minimum 5 years) from all patients referred to the Leeds HF Service for 12 months of following the initiation of the NP-guideline-directed pathway. Between 1 May 2012 and 1 August 2013, 1020 people with symptoms possibly due to HF attended either with a raised NT-pro-BNP or a previous myocardial infarction (MI) with an overall rate of left ventricular systolic dysfunction (LVSD) of 33%. Of these, 991 satisfied the ESC criteria (NT-pro-BNP ≥125 pg/mL) in whom the rate of LVSD was 32%, and 821 the UK-NICE criteria in whom the rate of LVSD was 49% in those with a previous MI, 25% in those with NT-pro-BNP concentration 400-2000 pg/mL, and 54% in those with NT-pro-BNP concentration of >2000 pg/mL. An NT-pro-BNP concentration 125-400 pg/mL had a 12% risk of LVSD. Specificity was poor in women >70 years, who made up the largest proportion of attendees. Elevated NT-pro-BNP levels were associated with lower survival even in the absence of LVSD.. In people referred through the ESC and UK-NICE guidelines, elevated NT-pro-BNP is a marker of increased mortality risk, but there is wide variation in specificity for LVSD. Age- and sex-adjusted criteria might improve performance.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Primary Health Care; Prospective Studies; Referral and Consultation; Secondary Care; Time Factors; United Kingdom

This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug.. We enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R. Sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Biphenyl Compounds; CD146 Antigen; Chronic Disease; Dose-Response Relationship, Drug; Drug Combinations; Echocardiography; Female; Fructosamine; Glucagon-Like Peptide 1; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Substance P; Tetrazoles; Treatment Outcome; Troponin I; Valsartan

Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF.. The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events.. Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations.. Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.

Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Cytokines; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Inflammation; Interleukin-11; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Prognosis; Proportional Hazards Models; Prospective Studies; ROC Curve; Ventricular Function, Left

To describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries.. We identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995-2005 vs period 2: 2006-2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses.. Among 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33-105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics.. Ambulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Chronic Disease; Female; Germany; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Norway; Outpatients; Peptide Fragments; Platelet Aggregation Inhibitors; Prognosis; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; United Kingdom

To elucidate clinical and diagnostic features of chronic heart failure (CHF) in patients with chronic obstructive pulmonary disease (COPD).. The study included 239 patients with COPD and 42 patients with CHF without COPD. The first subgroup consisted of 60 patients with a history of myocardial infarction (MI) and the second subgroup consisted of 79 patients without a history of MI. A general clinical examination, EchoCG, measurements of N-terminal pro B-type natriuretic peptide (NT-proBNP), galectin 3, and high-sensitivity C-reactive protein (hsCRP) were performed for all patients.. The risk group for excluding HF as a cause of progressive dyspnea in COPD patients consisted of patients with the bronchitic phenotype who belonged to GOLD groups C and D with frequent exacerbations, increased hsCRP, reduced oxygen saturation, and impaired exercise tolerance. Patients with a history of MI constituted a special group of risk. Measuring specific biomarkers, primarily BNP or NT-proBNP, is recommended to confirm the presence/absence of CHF and to evaluate CHF severity in patients with these risk factors.. A combination of COPD and CHF produces a number of clinical and, specifically, diagnostic problems, which have not been completely solved so far.

Topics: Biomarkers; Chronic Disease; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive

According to guidelines, the prognosis of patients with chronic heart failure can be predicted by determining the levels of natriuretic peptides, the NYHA classification and comorbidities. The aim our work was to develop a prognostic score in chronic heart failure patients that would take account of patients' comorbidities, NYHA and NT-proBNP levels.. A total of 1,088 patients with chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40-49%) were enrolled consecutively. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (EP). The occurrence of EP was 14.9% and grew with higher NYHA, namely 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III-IV) (p<0.001). The occurrence of EP was 3%, 10% and 15-37% in patients with NT-proBNP levels ≤125 ng/L, 126-1000 ng/L and >1000 ng/L respectively. Discrimination abilities of NYHA and NT-proBNP were AUC 0.670 (p<0.001) and AUC 0.722 (p<0.001) respectively. The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and being on a higher dose of furosemide (>40 mg daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790).. The use of prediction models in patients with chronic heart failure, namely those taking account of natriuretic peptides, should become a standard in routine clinical practice. It might contribute to a better identification of a high-risk group of patients in which more intense treatment needs to be considered, such as heart transplantation or LVAD implantation.

Topics: Aged; Area Under Curve; Biomarkers; Chronic Disease; Female; Heart Failure; Heart Transplantation; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries; ROC Curve; Stroke Volume

Topics: Aged; Atrial Fibrillation; China; Chronic Disease; Cognitive Dysfunction; Coronary Artery Disease; Diabetes Mellitus; Female; Heart Failure; Hospitalization; Humans; Hypertension; India; Malaysia; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Singapore; Smoking; Stroke; Troponin T

Patients with pulmonary arterial hypertension (PAH) and distal chronic thromboembolic pulmonary hypertension (CTEPH) who still reveal risk factors of worse prognosis on double combination therapy may benefit from add-on therapy with the novel oral selective prostacyclin receptor agonist selexipag.. We reviewed all patients with PAH/distal CTEPH in the Zurich cohort who received selexipag as add-on to oral combination therapy and retrieved New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), NT-pro-BNP, quality of life questionnaires (CAMPHOR and EuroQoL), tricuspid pressure gradient (TPG) by echocardiography and cardiopulmonary exercise test parameters (power output and oxygen uptake).. Twenty-three patients with PAH/CTEPH (20/3), 14 females, median (quartiles) age 56 (46; 66) years received an oral triple therapy containing selexipag at a median dose of 2000 (1600; 3100) mcg during 221 (113; 359) days. The following parameters were stabilized from baseline to last FU: 6MWD (440 (420; 490) to 464 (420; 526) m), NYHA class (three to two), NT-pro-BNP (326 (167; 1725) to 568 (135; 1856)  ng/l), TPG, power output, and oxygen uptake. Quality of life reflected by the CAMPHOR and EuroQoL improved.. Early initiation of triple oral combination therapy including selexipag in PAH/CTEPH with intermediate risk factor profile may help to stabilize functional class, exercise performance, and pulmonary hemodynamics in a real-life setting and potentially improves quality of life. Whether these beneficial effects can be truly attributed to the addition of selexipag should be addressed in future randomized controlled trials.

Topics: Acetamides; Aged; Antihypertensive Agents; Chronic Disease; Cohort Studies; Drug Therapy, Combination; Echocardiography; Endothelin Receptor Antagonists; Enzyme Activators; Exercise Test; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Pulmonary Arterial Hypertension; Pulmonary Embolism; Pyrazines; Quality of Life; Retrospective Studies; Soluble Guanylyl Cyclase; Tricuspid Valve; Walk Test

Fractalkine has been reported to play an important role in the pathophysiology of various cardiovascular disorders. This research aims to study the change of soluble fractalkine (sFKN) in plasma level of patients with chronic heart failure (CHF) and evaluate its prognostic value.A total of 96 patients with CHF and 45 healthy subjects were included in this study. The plasma levels of sFKN, brain natriuretic peptide (BNP), and Interleukin-18 (IL-18) were determined by ELISA kits when they were first admitted to the hospital. Left ventricular ejection fraction (LVEF) was measured by echocardiogram. Rehospitalization status within 1 year after the first hospitalization was also recorded.The plasma levels of sFKN, BNP, and IL-18 in patients with CHF were significantly higher than in the control group (P < 0.05). The concentrations of sFKN and BNP were increased with the severity of heart failure classified by NYHA classification (P < 0.05). There were no statistical differences among all CHF subgroups classified by etiology (P > 0.05). Plasma sFKN level in CHF group was positively correlated with BNP (r = 0.441, P < 0.001) and IL-18 (r = 0.592, P < 0.001). Receiver operating characteristic curve analysis showed that area under the curve values of FKN, BNP, and IL-18 were 0.885 (95%CI: 0.810 to 0.960, P < 0.001), 0.889 (95%CI: 0.842 to 0.956, P < 0.001), and 0.878 (95%CI: 0.801-0.954, P < 0.001), respectively. The concentrations of sFKN and BNP were increased in patients readmitted more than once within 1 year (P < 0.05).

Topics: Adult; Aged; Chemokine CX3CL1; Chronic Disease; Echocardiography; Female; Heart Failure; Humans; Interleukin-18; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Topics: Aged; Biomarkers; Chronic Disease; Cohort Studies; Coronary Artery Disease; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Revascularization; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

The exact relationship between serum myostatin and the severity and prognosis of chronic heart failure (CHF) is unclear. In this study, we investigated the association between serum myostatin and the severity and prognosis in patients with CHF.. Two hundred and eighty-eight CHF patients and 62 healthy controls were studied. Cardiac ultrasound and serum myostatin, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were detected. CHF patients were divided into 3 groups according to tertiles of NT-proBNP or myostatin levels respectively.. Serum myostatin levels were higher in CHF patients than in controls. New York Heart Association (NYHA) class IV patients had the highest levels of serum myostatin among the four NYHA classes. Compared with the low tertile NT-proBNP group, serum myostatin levels were significantly higher in the moderate and high tertile groups (15.47 ± 4.25 vs. 14.18 ± 3.69 ng/mL, p = .026; 16.28 ± 5.34 vs. 14.18 ± 3.69 ng/mL, p = .002). During 51-months follow-up, of 173 patients there were 36 deaths. Compared to survivors, nonsurvivors had significantly higher serum myostatin (18.11 ± 4.52 vs. 14.85 ± 5.11 ng/mL, p < .01). Patients in the high tertile myostatin group had lower survival rate (73.95% vs. 93.75%; p < .05) and larger number of CHF rehospitalization than those in the low tertile group. Cox regression analysis showed that serum myostatin was an independent predictor of mortality.. Serum myostatin levels can reflect the severity of CHF and be a predictor of adverse prognosis in CHF patients.

Topics: Aged; Aged, 80 and over; Case-Control Studies; China; Chronic Disease; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Myostatin; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Survival Rate

Co-morbid atrial fibrillation (AF) increases both mortality and N-terminal pro brain natriuretic peptide (NT-proBNP) concentrations in patients with chronic heart failure (CHF). It is unclear whether AF worsens prognosis independently from NT-proBNP concentrations. If AF was an independent risk factor, NT-proBNP levels for outcome prediction would need to be adjusted in patients with AF. We aimed to analyse the influence of AF on the prognostic value of NT-proBNP in patients with CHF.. A total of 2541 consecutive CHF patients with sinus rhythm (SR) or AF were identified in the outpatients' CHF registry of the University of Heidelberg, Germany. Of these, 250 patients with SR were individually matched to 250 patients with AF with respect to NT-proBNP, New York Heart Association functional class, sex, age, and aetiology of CHF. In the general sample, both AF and NT-proBNP were associated with all-cause mortality [hazard ratio (HR) = 1.96, 95% confidence interval (CI) 1.61-2.39, P < 0.001; and HR = 1.03 per 1000 ng/L increase, 95% CI 1.02 to 1.04, P < 0.001, respectively]. After matching, NT-proBNP retained its prognostic power (HR = 1.13 per 1000 ng/L increase, 95% CI 1.10 to 1.16, P < 0.001), but AF did not (HR = 0.91, 95% CI 0.66 to 1.25, P = 0.56). Despite similar prognosis, matched patients with SR were in more advanced CHF than were AF patients as indicated by a lower left ventricular ejection fraction (30 ± 13% vs. 34 ± 14%, P < 0.001).. The prognostic value of NT-proBNP in CHF is not influenced by concomitant AF. AF, in return, might be a surrogate of a worse cardiac condition rather than an independent risk factor.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Secondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.. A total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow-up.. Of 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR-proADM (adj.OR 2.25, 95% CI 1.29-3.93; P = .004), MR-proANP (adj.OR 1.84, 95% CI 1.14-3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04-2.67; P = .035) and CT-pro-ET1 (adj.OR 1.68, 95% CI 1.06-2.68; P = .027) but not with NT-proBNP (P = .54).. Increased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT-proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures and MR-proADM, a marker of forward failure and peripheral released vasoactive CT-proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Disease Progression; Echocardiography; Endothelin-1; Female; Glycopeptides; Heart Failure, Systolic; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prognosis; Protein Precursors; Risk Assessment; Stroke Volume

Chronic mitral valve disease (CMVD) is the most common cardiovascular disease in dogs, causing decreased cardiac output that results in poor tissue perfusion and tissue damage to kidneys, pancreas, and other organs. The purpose of this study was to evaluate the relationships between heart disease severity and N-terminal pro B-type natriuretic peptide (NT-proBNP) and lipase in dogs with CMVD, as well as to evaluate longitudinal changes in these values. A total of 84 dogs participated in this 2015 to 2017 study. Serum values of NT-proBNP and lipase were analyzed; radiography was used to measure the vertebral heart score and assess various echocardiographic values. NT-proBNP showed a strong positive correlation with increasing stage of heart disease; lipase showed a mild positive correlation with heart disease stage. When the three values (NT-proBNP, lipase and month) were continuously measured at 6-month intervals, all showed a correlation with the increasing length of the disease.

Topics: Animals; Chronic Disease; Dog Diseases; Dogs; Echocardiography; Lipase; Longitudinal Studies; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Republic of Korea

Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events.. It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF).. We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay.. In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03-2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = -0.394), glomerular filtration fraction (GFR; ϱ = -0.615), and peak VO2 (ϱ = -0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age.. This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Immunoassay; Kynurenine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Stroke Volume; Ventricular Function, Left

Our study was to explore the roles between serum soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) while evaluating ventricular function to properly diagnose chronic heart failure (CHF).. In total, 197 CHF patients were recruited and classified into ventricular function's II, III, and IV groups, and 106 healthy people into normal control group. To detect concentrations of Sst2 and NT-proBNP, ELISA and electro-chemiluminescence immuno assay were implemented. An automatic biochemical analyzer was used to determine the levels of the following: blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and uric acid (UA). A receiver operating characteristic (ROC) curve was adopted to detect the diagnostic value sST2 and NT-ProBNP in CHF and the logistic regression analysis involving the risk factors of CHF.. Serum sST2 and NT-proBNP concentrations were increased significantly in the ventricular function's II, III, and IV groups in a manner dependent on concentration as opposed to the manner the normal control group occupied. The area under the curve (AUC) of sST2, found NT-proBNP and sST2+NT-proBNP to be 0.942 (95% CI: 0.917-0.966), 0.920 (95% CI: 0.891-0.948), and 0.968 (95% CI: 0.953-0.984), respectively. sST2, NT-proBNP, UA, and Cr were verified as important risk factors of CHF.. Serum sST2 and NT-ProBNP could act as diagnostic indicators for CHF.

Topics: Adult; Aged; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve

Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF.. We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair.. CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation.

Topics: Aged; Aged, 80 and over; Biomarkers; Chromogranin B; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Sensitivity and Specificity

Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls.. Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age-matched subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR).. Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT-proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C-reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = -.38) or estimated glomerular filtration rate (r = -.34) in CHF patients.. CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Biomarkers; Capillaries; Chronic Disease; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Glycocalyx; Heart Failure; Humans; Male; Microcirculation; Microscopy, Video; Microvascular Rarefaction; Microvessels; Middle Aged; Mouth Floor; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Count; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left; Vitamin K

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left

Recent ESC guidelines on heart failure (HF) have introduced a new phenotype based on left ventricular ejection fraction (LVEF), called the mid-range (HFmrEF). This phenotype falls between the classical reduced (HFrEF) and preserved (HFpEF) HF phenotypes. We aimed to characterize the HFmrEF biomarker profile and outcomes.. 1069 consecutive ambulatory patients were included in the study (age 66.2 ± 12.8 years); 800 with HFrEF (74.8%), 134 with HFmrEF (12.5%), and 135 with HFpEF (12.5%). We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenicity (ST2), galectin-3, high-sensitivity C-reactive protein, cystatin-C, neprilysin, and soluble transferrin receptor, during 4.9 ± 2.8 years of follow-up. The primary end-point was the composite: cardiovascular death or HF-related hospitalization. We also examined all-cause, cardiovascular death, and the composite: all-cause death or HF-related hospitalization.. NTproBNP levels in HFmrEF were similar to levels in HFpEF, but significantly lower than levels in HFrEF. No other studied biomarkers were different between HFmrEF and HFrEF. All biomarkers, except neprilysin, showed higher risk prediction capabilities in HFmrEF than in HFrEF or HFpEF. The largest difference between HFrEF and HFmrEF was the hs-TnT level (hazard ratio [HR]: 4.72, 95% CI: 2.81-7.94 vs. HR: 1.67, 95%CI: 1.74-1.89; all p < 0.001).. Although HFmrEF is acknowledged as an intermediate phenotype between HFrEF and HFpEF, from a multi-biomarker point of view, HFmrEF was similar to HFrEF, except that NTproBNP levels were lower. Biomarkers commonly used for HFrEF risk prediction are more valuable for HFmrEF risk stratification.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Death; Female; Follow-Up Studies; Galectin 3; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Troponin T

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Chronic Disease; Cohort Studies; Databases, Factual; Echocardiography; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Precision Medicine; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Regression Analysis; Retrospective Studies; Risk Assessment; Sex Factors; Survival Analysis; Troponin T

Topics: Aged; Chronic Disease; Databases, Factual; Female; Heart Failure; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome

To explore the association between sarcopenia (SAR) and long-term prognosis of patients with chronic heart failure (CHF) aged 70 years and over, 182 CHF patients from January 1, 2012 to December 31, 2014 were included in the present study. The patients were divided into the SAR group and the non-SAR group. The median follow-up period was 36 (3, 57) months. The endpoint was any heart failure-related event (HFRE). There were significant differences in age, body mass index, hemoglobin, B-type natriuretic peptide, hypersensitive troponin T (hs-TnT), left ventricular ejection fraction (LVEF) and cardiac function class between the two groups (all. 为观察肌少症对70岁及以上慢性心力衰竭（CHF）患者远期预后的影响，对年龄≥70岁的182例CHF患者进行为期至少2年的随访，根据患者是否存在肌少症分为肌少症组和非肌少症组，记录一般临床资料。终点事件为心力衰竭相关事件(HFRE)。结果2组间年龄、体重指数、血红蛋白、B型利钠肽、超敏肌钙蛋白T、左心室射血分数和纽约心脏病协会(NYHA)心功能分级差异有统计学意义（

Topics: Aged; Aged, 80 and over; Chronic Disease; Heart Failure; Humans; Kaplan-Meier Estimate; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Sarcopenia; Severity of Illness Index; Troponin T; Ventricular Function, Left

BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to detect levels of inflammatory cytokines, superoxide dismutase (SOD), and malondialdehyde (MDA). RESULTS In the CHF group, compared with the sham operation group, there was an increase in the heart weight to body weight ratio (HW/BW), the left ventricular weight to body weight ratio (LVW/BW), the left ventricular end diastolic diameter (LVEDD), the left ventricular end systolic diameter (LVESD), plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels, the cardiac collagen volume fraction (CVF), apoptotic index, expression levels of collagen I, collagen III, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in the myocardial tissue, and a decrease in the left ventricular shortening fraction (LVFS) and left ventricular ejection fraction (LVEF), and cardiac superoxide dismutase (SOD) activity. These changes were corrected in the SFN-treated group. CONCLUSIONS In a rabbit model of CHF, treatment with SFN improved cardiac function and remodeling by inhibiting oxidative stress and inflammation.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Chronic Disease; Collagen; Cytokines; Female; Fibrosis; Heart Failure; Heart Function Tests; Hemodynamics; Inflammation; Isothiocyanates; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Rabbits; RNA, Messenger; Sulfoxides

Background The Seattle heart failure model or the cardiac and comorbid conditions (3C-HF) scores may help define patient risk in heart failure. Direct comparisons between them or versus N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) have never been performed. Methods Data from consecutive patients with stable systolic heart failure and 3C-HF data were examined. A subgroup of patients had the Seattle heart failure model data available. The endpoints were one year all-cause or cardiovascular death. Results The population included 2023 patients, aged 68 ± 12 years, 75% were men. At the one year time-point, 198 deaths were recorded (10%), 124 of them (63%) from cardiovascular causes. While areas under the curve were not significantly different, NT-proBNP displayed better reclassification capability than the 3C-HF score for the prediction of one year all-cause and cardiovascular death. Adding NT-proBNP to the 3C-HF score resulted in a significant improvement in risk prediction. Among patients with Seattle heart failure model data available ( n = 798), the area under the curve values for all-cause and cardiovascular death were similar for the Seattle heart failure model score (0.790 and 0.820), NT-proBNP (0.783 and 0.803), and the 3C-HF score (0.770 and 0.800). The combination of the 3C-HF score and NT-proBNP displayed a similar prognostic performance to the Seattle heart failure model score for both endpoints. Adding NT-proBNP to the Seattle heart failure model score performed better than the Seattle heart failure model alone in terms of reclassification, but not discrimination. Conclusions Among systolic heart failure patients, NT-proBNP levels had better reclassification capability for all-cause and cardiovascular death than the 3C-HF score. The inclusion of NT-proBNP to the 3C-HF and Seattle heart failure model score resulted in significantly better risk stratification.

Topics: Aged; Aged, 80 and over; Biomarkers; Cause of Death; Chronic Disease; Comorbidity; Decision Support Techniques; Female; Heart Failure, Systolic; Humans; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Registries; Retrospective Studies; Risk Assessment; Risk Factors

The latest pulmonary hypertension (PH) guidelines define therapeutic goals in terms of symptoms, exercise capacity, and haemodynamics for patients with pulmonary arterial hypertension (PAH) and recommend advanced combined medical therapy. For inoperable or post-surgical residual distal chronic thromboembolic PH (CTEPH) medical treatment is similarly advised.. We analysed whether risk factor goals are achieved and combination therapy is used in prevalent patients with PAH or distal CTEPH.. PAH or distal CTEPH patients who were seen at the University Hospital Zurich during the last year were analysed in terms of demography, clinical data, medication, and therapeutic goals. Achievement of therapeutic goals was defined as New York Heart Association (NYHA) class ≤II, N-terminal pro-brain natriuretic peptide (NTpro-BNP) < 300 ng/L, and 6-min walking distance (6MWD) > 440 m.. A total of 108 PAH patients (age 59 ± 18 years, 62% female, 64% idiopathic, 36% associated) and 38 distal CTEPH patients (age 69 ± 14 years, 55% female) were included. They had been diagnosed on average 66 ± 48 months (±SD) previously. The percentage of PAH/CTEPH patients with NYHA ≤II was 52/53, respectfully, the percentage of those with NTproBNP < 300 ng/L was 61/52, and with 6MWD > 440 m 63/50. Overall, 33/31% fulfilled 3 and 29/35% fulfilled 2 of these goals. Regarding therapy, 43% of PAH patients were on double and 10% on triple combination therapy, whereas 16% of distal CTEPH patients were on double and 3% on triple combination therapy.. In this real-life cohort of prevalent patients with PAH or distal CTEPH, targeted drug therapy resulted in an achievement of ≥2/3 predefined therapeutic goals in 2/3 of patients. Patients with PAH were more likely to receive combination therapy compared to CTEPH patients.

Topics: Adult; Aged; Antihypertensive Agents; Body Mass Index; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Thromboembolism; Treatment Outcome; Walk Test

Inferior vena cava (IVC) ultrasonography has been used for the diagnosis and prognosis of acute heart failure (HF). Its usefulness in chronic HF is less known.. IVC ultrasonography is a useful tool in the care of patients with chronic HF.. For this prospective cohort study, 95 patients with chronic HF were included consecutively as they attended scheduled medical visits. Ultrasound was done with a 5-MHz convex probe device, calculating IVC collapse index (IVCCI). Follow-up time was 1 year. Outcome events were worsening HF, hospital admission for HF, HF mortality, and all-cause mortality.. Worsening HF occurred in 70.9% of patients with IVCCI <30% and 39.1% of patients with IVCCI >50%, with a hazard ratio (HR) of 2.8 (95% CI: 1.3-6.2) adjusted by multivariable analysis. Regarding hospitalization, 45.3% of patients with IVCCI <30% required admission, compared with 5.9% of patients with IVCCI >50%; the adjusted HR was 13.9 (95% CI: 1.7-113.0). Mortality was higher in the IVCCI <30% group, with 25.7% all-cause mortality and 18.6% HF mortality, whereas in the IVCCI >50% group these values were 13% and 4.7%, respectively. However, these differences did not reach statistical significance. ROC analysis was performed and the AUC for IVCCI was not higher than that for NTproBNP for any of the outcomes studied.. IVC ultrasonography is a useful tool in follow-up of patients with chronic HF, allowing identification of patients at high risk of worsening and hospitalization. However, its usefulness is not higher than that of NTproBNP.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Area Under Curve; Biomarkers; Cause of Death; Chronic Disease; Disease Progression; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Outpatients; Patient Admission; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; Risk Factors; ROC Curve; Time Factors; Ultrasonography; Vena Cava, Inferior

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ± 6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Echocardiography; Female; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Left ventricular systolic dysfunction (LVSD) and cardiac decompensation often accompany AECOPD. Differentiation between the two is difficult and mainly relies on clinical and echocardiographic diagnostic procedures. The value of biomarkers, such as NT-proBNP, as diagnostic tools is still insufficiently investigated. The main goals of this trial were to investigate the value of NT-proBNP as a diagnostic tool for LVSD in AECOPD patients and determine its cut-off value which could reliably diagnose LVSD during AECOPD.. This trial prospectively enrolled 209 patients with AECOPD. The patients were divided into four groups-AECOPD plus chronic pulmonary heart disease (CPHD) with or without left ventricular compromise (LVSD), and AECOPD patients without CPHD with or without LVSD. NT-proBNP was measured within first 48 h of hospitalization.. Majority of patients were male (61%) active smokers (41.6%), average age of 68 years. High quality of echocardiography was obtained in 63.3 and 22.5% of the patients had LVSD. Average value of NT-proBNP in patients with LVSD was 3303.2 vs. 1092.5 pg/mL in patients without LVSD. Significant differences in NT-proBNP value (p = 0.0001) were determined between observed patient groups. At the cut-off value of 1505 pg/mL, sensitivity, specificity, and positive and negative predictive values are 76.6, 83.3, 57.1, and 92.47%, respectively.. At the cut-off value of 1505 pg/mL NT-proBNP could be used as a diagnostic marker for LVSD in acute exacerbation of COPD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Disease Progression; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Sensitivity and Specificity; Systole; Ventricular Dysfunction, Left

Prognostic models for patients with chronic heart failure are generally based on a single assessment but treatment is often given with the intention of changing risk; re- evaluation of risk is an important aspect of care. The prognostic value of serial measurements of natriuretic peptides for the assessment of changes in risk is uncertain.. To evaluate the prognostic value of serial measurements of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) during follow-up of out-patients with chronic heart failure (CHF).. Patients diagnosed with CHF between 2001 and 2014 at a single out-patient clinic serving a local community were included in this analysis. NT-proBNP was measured at the initial visit and serially during follow-up. Only patients who had one or more measurements of NT-proBNP after baseline, at 4, 12 and/or 24 months were included.. At baseline, amongst 1998 patients enrolled, the median age was 73 (IQR: 64-79) years, 70% were men, 31% were in NYHA class III/IV, and 77% had NT-proBNP >400 pg/mL. Median follow-up was 4.8 (IQR: 2.5-8.6) years. Serial measurements of NT-proBNP improved prediction of all-cause mortality at 3 years (c- statistic = 0.71) compared with using baseline data only (c-statistic = 0.67; p < 0.001) but a model using only the most recent NT-proBNP had an even higher c-statistic (0.72; p < 0.001). Similar results were obtained based on long-term prediction of mortality using all available follow-up data.. Serial measurement of NT-proBNP in patients with CHF improves prediction of all-cause mortality. However, using the most recent value of NT-proBNP has similar predictive power as using serial measurements.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prospective Studies; Risk Assessment

Topics: Cholesterol, HDL; Cholesterol, LDL; Chronic Disease; Creatinine; Depression; Dyslipidemias; Heart Failure; Humans; Natriuretic Peptide, Brain; Triglycerides

Introduction An inverse relationship between natriuretic peptides (N‑terminal fragment of the prohormone brain natriuretic peptide [NT‑proBNP]) and body mass index (BMI) among healthy people and patients with chronic heart failure (CHF) was observed. Objectives The aim of the study was to assess the relationship between nutritional status and NT‑proBNP concentrations in older persons. Patients and methods NT‑proBNP concentrations, medical histories, and malnutrition risk using Mini Nutritional Assessment were evaluated. Body composition was measured with dual energy X‑ray absorptiometry. The relationship of nutritional status with NT‑proBNP concentrations (in tertiles) was assessed. Results The mean (SD) age of 106 participants was 72.16 (9.38) years. Heart failure was diagnosed in 72.6% of patients. The risk of malnutrition was recognized in 28.3%, and the percentage of patients at risk increased in subsequent NT‑proBNP tertiles: from 16.7% in the first tertile to 48.6% in the third tertile (P = 0.005). The risk of malnutrition was associated with an increase in NT‑proBNP concentrations per tertile (odds ratio [OR], 2.30; 95% CI, 1.30-4.07; P = 0.004). Based on a multivariable logistic model, the NT‑proBNP concentration in the third tertile was associated with an over 9‑fold higher risk of malnutrition (OR, 9.80; 95% CI, 2.00-48.17; P = 0.005) as compared with the lowest concentration. Among patients with CHF, the relationship between NT‑proBNP and nutritional status was even stronger. Conclusions High NT‑proBNP levels contribute to increased risk of malnutrition in older patients with heart failure. In patients with elevated NT‑proBNP levels, the risk of malnutrition should be assessed.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Malnutrition; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk

Circulating concentrations of N-terminal fragment of the prohormone of brain natriuretic peptide (NT-proBNP) are influenced by age and common age-related comorbidities, such as renal dysfunction. Therefore, utility of NT-proBNP for prediction of prognosis in the aged has been questioned. We aimed to investigate the prognostic value of NT-proBNP across age classes in a cohort of patients with chronic systolic HF.. We enrolled 2364 consecutive outpatients with HF and left ventricular ejection fraction ≤50%. Patients were classified according to age quartiles, and a very elderly subgroup was identified, aged ≥85 years. After baseline assessment (including NT-proBNP testing), patients were followed-up for the composite of cardiovascular death, heart transplantation or ventricular assistance device implantation (primary outcome) and for all-cause death (secondary outcome). Patients in the fourth quartile (Q4, age ≥ 77 years, n = 638) and in the very elderly subgroup (age ≥ 85 years, n = 153), had higher NT-proBNP (p < .001 vs Q1). NT-proBNP was independently associated with primary and secondary outcome at 1- and 5-years follow-up in the whole population, as well as in Q4 and in the very elderly subgroup (all p < .05). Compared to the whole population, Q4 and very elderly had higher NT-proBNP cut-off for prediction of 1-year primary (4188 and 9729 ng/l, respectively vs 3710 ng/l) and secondary outcome (4296 and 7634 ng/l, respectively vs 3056 ng/l).. NT-proBNP predicts mortality in elderly and very elderly patients with chronic systolic HF, both at mid- and long-term follow-up. Higher NT-proBNP prognostic cut-off should be considered in the aged HF population.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies

Balloon pulmonary angioplasty (BPA) is an interventional treatment modality for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Therapy monitoring, based on non-invasive biomarkers, is a clinical challenge. This post-hoc study aimed to assess dynamics of high-sensitivity cardiac troponin T (hs-cTnT) as a marker for myocardial damage and its relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as a marker for cardiac wall stress.. This study included 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between 3/2014 and 3/2017. Biomarker measurement was performed consecutively prior to each BPA and at 6-MFU. In total, the 51 patients underwent an average of 5 BPA procedures. The 6-month survival rate was 96.1%. The baseline (BL) meanPAP (39.5±12.1mmHg) and PVR (515.8±219.2dyn×sec×cm-5) decreased significantly within the 6-MFU (meanPAP: 32.6±12.6mmHg, P<0.001; PVR: 396.9±182.6dyn×sec×cm-5, P<0.001). At BL, the median hs-cTnT level was 11 (IQR 6-16) ng/L and the median NT-proBNP level was 820 (IQR 153-1872) ng/L. The levels of both biomarkers decreased steadily after every BPA, showing the first significant difference after the first procedure. Within the 6-MFU, hs-cTnT levels (7 [IQR 5-12] ng/L; P<0.001) and NT-proBNP levels (159 [IQR 84-464] ng/l; P<0.001) continued to decrease. The hs-cTnT levels correlated with the PVR (rrs = 0.42; p = 0.005), the meanPAP (rrs = 0.32; p = 0.029) and the NT-proBNP (rrs = 0.51; p<0.001) levels at BL.. Non-invasive biomarker measurement provides valuable evidence for the decreasing impairment of myocardial function and structure during BPA therapy. Changes in hs-cTNT levels are suggestive for a reduction in ongoing myocardial damage.

Topics: Aged; Angioplasty, Balloon; Biomarkers; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Circulation; Pulmonary Embolism; Treatment Outcome; Troponin T

Background The Get With the Guidelines-Heart Failure ( GWTG - HF ) risk score was developed using American Heart Association GWTG - HF program data and predicts in-hospital mortality in patients with acute heart failure (HF). We aimed to clarify the prognostic impacts of the GWTG - HF risk score in patients with HF after discharge. Methods and Results We examined the GWTG - HF score in 1452 patients with HF, who were admitted to our hospital and discharged after treatment, by calculating 7 predetermined variables. We divided all subjects into 3 groups according to the GWTG - HF risk score (low, moderate, and high score groups). The plasma B-type natriuretic peptide level significantly increased with increasing GWTG - HF risk score severity (median values of B-type natriuretic peptide: 167.0 in low, 260.7 in moderate, and 418.2 pg/mL in high score groups). We followed up all subjects after discharge, and there were 347 (23.9%) all-cause deaths and 407 (28.0%) cardiac events in follow-up periods. A Kaplan-Meier survival curve demonstrated that event rates of all-cause death and cardiovascular events, including worsening HF and cardiac death, significantly increased with increasing GWTG - HF risk score severity in all subjects, and also in 749 patients with HF with preserved ejection fraction (ejection fraction ≥50%) and 703 patients with HF with reduced ejection fraction (ejection fraction <50%) patients. The multivariable Cox proportional hazard regression analysis demonstrated that the GWTG - HF risk score was one of the significant predictors of all-cause mortality and cardiac events (all-cause mortality: hazard ratio, 1.537, 95% confidence interval, 1.172-2.023; cardiac events: hazard ratio, 1.584, 95% confidence interval, 1.344-1.860, per 10-point increase of GWTG - HF score). Conclusions The GWTG - HF risk score is a useful multivariable score model for several years after hospitalization in patients with HF in a Japanese population.

Topics: Acute Disease; Adult; Age Factors; Aged; Blood Pressure; Blood Urea Nitrogen; Cause of Death; Chronic Disease; Comorbidity; Disease Progression; Ethnicity; Female; Heart Diseases; Heart Failure; Heart Rate; Hospital Mortality; Hospitalization; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Sodium

Background The Meta-Analysis Global Group in Chronic Heart Failure ( MAGGIC ) mortality risk score, derived from a large sample of patients with heart failure ( HF ) across the spectrum of ejection fraction ( EF ), has not yet been externally validated in a well-characterized HF with preserved EF cohort with adjudicated morbidity outcomes. Methods and Results We evaluated the MAGGIC risk score (composed of 13 clinical variables) in 407 patients with HF with preserved EF enrolled in a prospective registry and used Cox regression to evaluate its association with morbidity/mortality. We used receiver-operating characteristic analysis to compare the predictive ability of the MAGGIC risk score with the more complex Seattle Heart Failure Model, and we determined the value of adding B-type natriuretic peptide to the MAGGIC risk score for risk prediction. During a mean follow-up time of 3.6±1.8 years, 28% died, 32% were hospitalized for HF , and 55% had a cardiovascular hospitalization and/or death. The MAGGIC score, a mean± SD of 18±7, was significantly associated with mortality ( P<0.0001), HF hospitalizations ( P<0.0001), and the combined end point of cardiovascular-related hospitalizations or death (hazard ratio, 1.8 [95% confidence interval, 1.6-2.1], per 1- SD increase in the MAGGIC score; P<0.0001). Receiver-operating characteristic analyses showed that MAGGIC and Seattle Heart Failure Model performed similarly in predicting HF with preserved EF outcomes, but the MAGGIC score demonstrated better calibration for hospitalization outcomes. Further analyses showed that B-type natriuretic peptide was additive to the MAGGIC risk score for predicting outcomes ( P<0.01 by likelihood ratio test). Conclusions The MAGGIC risk score is a simple, yet powerful method of risk stratification for both morbidity and mortality in HF with preserved EF . Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01030991.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Prospective Studies; Risk Assessment; ROC Curve; Stroke Volume; United States

Soluble suppression of tumorigenesis-2 (sST2) is a biomarker related to inflammation and fibrosis.. This study assessed the independent prognostic value of sST2 in chronic heart failure (HF).. Individual patient data from studies that assessed sST2 for risk prediction in chronic HF, together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT), were retrieved.. A total of 4,268 patients were evaluated (median age 68 years, 75% males, 65% with ischemic HF, 87% with left ventricular ejection fraction [LVEF] <40%). NT-proBNP, hs-TnT, and sST2 were 1,360 ng/l (interquartile interval: 513 to 3,222 ng/l), 18 ng/l (interquartile interval: 9 to 33 ng/l), and 27 ng/l (interquartile interval: 20 to 39 ng/l), respectively. During a 2.4-year median follow-up, 1,319 patients (31%) experienced all-cause death (n = 932 [22%] for cardiovascular causes). Among the 4,118 patients (96%) with available data, 1,029 (24%) were hospitalized at least once for worsening HF over 2.2 years. The best sST2 cutoff for the prediction of all-cause and cardiovascular death and HF hospitalization was 28 ng/ml, with good performance at Kaplan-Meier analysis (log-rank: 117.6, 61.0, and 88.6, respectively; all p < 0.001). In a model that included age, sex, body mass index, ischemic etiology, LVEF, New York Heart Association functional class, glomerular filtration rate, HF medical therapy, NT-proBNP, and hs-TnT, the risk of all-cause death, cardiovascular death, and HF hospitalization increased by 26%, 25%, and 30%, respectively, per each doubling of sST2. sST2 retained its independent prognostic value across most population subgroups.. sST2 yielded strong, independent predictive value for all-cause and cardiovascular mortality, and HF hospitalization in chronic HF, and deserves consideration to be part of a multimarker panel together with NT-proBNP and hs-TnT.

Topics: Aged; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Treatment Outcome; Troponin T

In clinical practice, a risk prediction model is an effective solitary program to predict prognosis in particular patient groups. B-type natriuretic peptide (BNP)and N-terminal pro-b-type natriuretic peptide (NT-proBNP) are widely recognized outcome-predicting factors for patients with heart failure (HF).This study derived external validation of a risk score to predict 1-year mortality after discharge in hospitalized patients with HF using the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)program data. We also assessed the effect of adding BNP or NT-proBNP to this risk score model in a Korean HF registry population.. We included 5625 patients from the Korean acute heart failure registry (KorAHF) and excluded those who died in hospital. The MAGGIC constructed a risk score to predict mortality in patients with HF by using 13 routinely available patient characteristics (age, gender, diabetes, chronic obstructive pulmonary disorder (COPD), HF diagnosed within the last 18 months, current smoker, NYHA class, use of beta blocker, ACEI or ARB, body mass index, systolic blood pressure, creatinine, and EF). We added BNP or NT-proBNP, which are the most important biomarkers, to the MAGGIC risk scoring system in patients with HF. The outcome measure was 1-year mortality. In multivariable analysis, BNP or NT-proBNP independently predicted death. The risk score was significantly varied between alive and dead groups (30.61 ± 6.32 vs. 24.80 ± 6.81, p < 0.001). After the conjoint use of BNP or NT-proBNP and MAGGIC risk score in patients with HF, a significant difference in risk score was noted (31.23 ± 6.46 vs. 25.25 ± 6.96, p < 0.001).The discrimination abilities of the risk score model with and without biomarker showed minimal improvement (C index of 0.734 for MAGGIC risk score and 0.736 for MAGGIC risk score plus BNP or NT-proBNP, p = 0.0502) and the calibration was found good. However, we achieved a significant improvement in net reclassification and integrated discrimination for mortality (NRI of 33.4%,p < 0.0001 and IDI of 0.002, p < 0.0001).. In the KorAHF, the MAGGIC project HF risk score performed well in a large nationwide contemporary external validation cohort. Furthermore, the addition of BNP or NT-proBNPto the MAGGIC risk score was beneficial in predicting more death in hospitalized patients with HF.

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors

The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients.. Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test.. Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001).. The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Chronic Disease; Czech Republic; Female; Heart Failure; Humans; Lipocalin-2; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries

The prevalence of chronic heart failure (CHF) remains high. Echocardiography is a reliable method of diagnosing heart failure. Determination of brain natriuretic peptide allows to identify patients with the most probable diagnosis of heart failure, which requires further instrumental examination of patients. To study the level of the brain natriuretic peptide in patients with diastolic chronic heart failure with preserved left ventricular ejection fraction.. The study included 96 outpatients with diastolic chronic heart failure I-III functional class with a preserved left ventricular ejection fraction at the age of 65.06 ± 1.15 years and 50 practically healthy people aged 39.90 ± 1.64 years as a control group who underwent a preventive examination. The level of the N-terminal fragment of the medullary natriuretic peptide (NT-proBNP) in serum was determined using a test system (Vector-Best, Russia).. The concentration of NT-proBNP in patients with diastolic heart failure with a preserved left ventricular ejection fraction was 108.18 ± 21.64 in the range from 0.0 to 1212.3 pg/ml compared to the control of 7.6 ± 1.38 pg/ml, p<0.05. A positive correlation was found between the concentration of NT-proBNP and the area of the left atrium (r=0.35), left ventricular E/e '(r=0.6), and left ventricular end-systolic volume (r=0.48). The level of NT-proBNP had no correlation with the functional class of CHF (r=0,23), as well as with the stage of CHF (r=0,23).. Thus, patients with diastolic CHF with a preserved ejection fraction in 67% of cases had a level of NT-proBNP in the blood less than the diagnostic threshold. The concentration of NT-proBNP in the serum positively correlates with increased pressure in the cavity of the left ventricle, the end-systolic volume in it and the area of the left atrium.

Topics: Aged; Chronic Disease; Correlation of Data; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Stroke Volume; Ventricular Function, Left

This study sought to evaluate whether a panel of biomarkers improved prognostication in patients with heart failure (HF) and reduced ejection fraction of ischemic origin using a systematized approach according to suggested requirements for validation of new biomarkers.. Modeling combinations of multiple circulating markers could potentially identify patients with HF at particularly high risk and aid in the selection of individualized therapy.. From a panel of 20 inflammatory and extracellular matrix biomarkers, 2 different biomarker panels were created and added to the Seattle HF score and the prognostic model from the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study (n = 1,497), which included conventional clinical characteristics and C-reactive protein and N-terminal pro-B-type natriuretic peptide. Interactions with statin treatment were also assessed.. The two models-model 1 (endostatin, interleukin 8, soluble ST2, troponin T, galectin 3, and chemokine [C-C motif] ligand 21) and model 2 (troponin T, soluble ST2, galectin 3, pentraxin 3, and soluble tumor necrosis factor receptor 2)-significantly improved the CORONA and Seattle HF models but added only modestly to their Harrell's C statistic and net reclassification index. In addition, rosuvastatin had no effect on the levels of a wide range of inflammatory and extracellular matrix markers, but there was a tendency for patients with a lower level of biomarkers in the 2 panels to have a positive effect from statin treatment.. In the specific HF patient population studied, a multimarker approach using the particular panel of biomarkers measured was of limited clinical value for identifying future risk of adverse outcomes.

Topics: Biomarkers; Blood Proteins; C-Reactive Protein; Cardiovascular Diseases; Cause of Death; Chemokine CCL21; Chronic Disease; Endostatins; Galectin 3; Galectins; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-8; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Rosuvastatin Calcium; Serum Amyloid P-Component; Troponin T

Balloon pulmonary angioplasty (BPA) is a developing treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, to our knowledge there are no published data on BPA in CTEPH subjects aged 75 or over. The aim of the study was to analyze clinical and hemodynamic outcomes of sequential BPA in very elderly patients disqualified from pulmonary endarterectomy (PEA).. We enrolled 10 patients (4 male, 6 female, median age 81 [75-88]) with confirmed CTEPH, mPAP > 30 mmHg, and WHO class > II, disqualified from PEA. Overall, 10 patients underwent 39 BPA sessions (mean 3.9 sessions per patient, range 1-9), and 70 pulmonary arteries were dilated, (mean 6.5 vessels per patient, range 1-14).. Pulmonary angioplasty resulted in significant clinical and hemodynamic improvement in every patient: 6 MWT distance increased from a median of 221 m (80-320) to 345 (230-455) and plasma NT-proBNP levels decreased (P < 0.01). Sequential BPA resulted in normalization of mPAP (<25 mmHg) in 6 of 10 patients and mPAP decreased to 25-30 mmHg in three others. In the whole group mPAP decreased from 41 (31-53) mmHg to 23 (17-33) mmHg (P < 0.01). Overall, mean PAP and PVR decreased significantly in all cases, while CO and CI increased (P < 0.01). No severe complications occurred during BPA and over a median follow-up of 553 days (range 81-784), and all patients are still alive and in good general health.. This study demonstrated the safety and efficacy of refined BPA in CTEPH patients aged 75 or over, disqualified from PEA. Refined BPA may emerge as an alternative therapeutic strategy in very elderly CTEPH patients who are suitable for surgery, but this requires further validation in a large prospective study.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Chronic Disease; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prospective Studies; Pulmonary Artery; Pulmonary Embolism; Risk Adjustment; Treatment Outcome

BACKGROUND Chronic heart failure (CHF) is a leading cause of death worldwide. A long noncoding RNA (lncRNA) named urothelial carcinoma associated 1 (UCA1) is important in multiple diseases. However, the role of UCA1 in CHF is still unknown. Our study investigated whether UCA1 could be applied as an ideal marker to diagnose and evaluate prognosis in CHF. MATERIAL AND METHODS Total plasma RNA was extracted from 67 CHF patients and 67 controls. Quantitative real-time polymerase chain reaction was used to determine the plasma level of UCA1. Correlations between UCA1 and clinical parameters were analyzed by Pearson correlation. Receiver operating characteristic curves (ROC) were obtained to analyze the predictive power of UCA1 and BNP for CHF. Kaplan-Meier survival curves were used to evaluate prognosis of CHF within 1 year. RESULTS There was no significant difference in elementary data between CHF and controls. Plasma UCA1 was much higher in CHF patients compared with controls. Plasma UCA1 was positively and negatively correlated with brain natriuretic peptide (BNP) and left ventricle ejection fraction (LVEF), respectively. Plasma UCA1 diagnosed CHF with a diagnostic power of 0.89 and a sensitivity and specificity of 100% [95% CI (0.9464-1)] and 76.12% [95%CI (0.6414-0.8569)] (P<0.05), respectively. CHF patients with higher plasma UCA1 had a lower survival rate than those with a lower level, and survival rate predicted by UCA1 had a similar tendency with BNP. However, there was no significant difference between these 2 markers in predicting the prognosis of CHF (P>0.05). CONCLUSIONS Plasma UCA1 might be an excellent indicator to diagnose CHF and it might predict poor outcomes of CHF.

Topics: Aged; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Prognosis; RNA, Long Noncoding; ROC Curve; Stroke Volume; Survival Rate

Heart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM).. A total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA.. Levels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p<0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p<0.0001, GDF-15 p=0.0394, suPAR p=0.0029, H-FABP p<0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p<0.0001) and diabetes (sST2 p=0.0021, GDF-15 p=0.0055, suPAR p=0.0339, H-FABP p=0.0010) were significantly associated with a rise in cardiac biomarkers.. Novel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.

Topics: Aged; Biomarkers; Cardiomyopathies; Case-Control Studies; Chronic Disease; Fatty Acid Binding Protein 3; Female; Germany; Growth Differentiation Factor 15; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Receptors, Urokinase Plasminogen Activator; Retrospective Studies; Ventricular Dysfunction, Left

Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown.. Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group). We analyzed the change from baseline to 6-12 months of riociguat treatment for the 6-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), partial pressure of oxygen in arterial blood (PaO2), brain natriuretic peptide (BNP), World Health Organization (WHO) functional class, safety and adverse events. The mPAP, BNP and WHO functional class significantly improved in total. In the transitioned group, BNP significantly decreased by -116.5±188.6pg/ml (P=0.0156). The 6MWD, mPAP, PVR, CI, and PaO2 improved but not significantly. The baseline condition was significantly more severe in the transitioned than in the new or add-on group. No patients discontinued riociguat. Relatively rapid transitioning from PDE5i to riociguat was safe under careful observation.. Transitioning to riociguat may be safe and effective in CTEPH patients with inadequate clinical responses to PDE5i.

Topics: Aged; Arterial Pressure; Chronic Disease; Drug Substitution; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Partial Pressure; Phosphodiesterase 5 Inhibitors; Pulmonary Artery; Pulmonary Embolism; Pyrazoles; Pyrimidines; Time Factors; Vascular Resistance; Walk Test

Biologic variation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) may affect blood levels and risk stratification. The sources of NT-proBNP variation are unknown.. We performed NT-proBNP measurements and clinical and hemodynamic assessments in 50 patients with heart failure with reduced ejection fraction (HFrEF) who met criteria for clinical stability over 2 time intervals. Hemodynamic variables were measured with the use of inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with the use of external electrocardiographic event recorders throughout the study. Determinants of NT-proBNP-levels and both absolute (ΔNT-proBNP. In patients with stable HFrEF, changes in clinical and hemodynamic variables only marginally contribute to the variation of NT-proBNP.

Topics: Aged; Chronic Disease; Electrocardiography; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

The study of the diagnostic value of biochemical markers of myocardial stress and inflammation in chronic heart failure (CHF) with different values of the ejection fraction (EF) of the left ventricle (LV).. The cross-sectional study included 105 patients aged 24 to 84 years (mean 58+/-14 years) with stable chronic heart failure I-II NYHA functional class classification. The causes of CHF were ischemic heart disease (IHD) in 33% of patients and arterial hypertension (AH) - 67%. All patients received medical treatment: angiotensin-converting enzyme (ACE) - 76%, -blockers - 72%, diuretics - 100%, statins - 80%. The control group consisted of 35 healthy volunteers. All subjects identified blood natriuretic peptide (NT-proBNP, ANP), adiponectin, galectin-3, pentraxins-3 and growth differentiation factor-15 (GDF-15) by enzyme immunoassay (ELISA). All surveyed performed transthoracic echocardiography (Echo).. The blood NT-proBNP, ANP, galectin-3, pentraxins and GDF-3-15 in patients with chronic heart failure was significantly higher than in the control group (p<0.001 in all cases). In contrast, the level of adiponectin was significantly higher than in healthy individuals - 11.90 (11.39; 12.65) vs 7.73 (3.58; 8.86) ng/ml in patients with chronic heart failure (p<0.001). LVEF ranged from 30 to 55%, in 33% of patients it was >50%. Correlation analysis Spearman found strong correlations (p<0.001 for all markers) between LVEF and the content of all the biomarkers, while between the PV and the level of adiponectin is a positive correlation was found (r=0.862), and between the PV and the other biomarkers - reverse (r from -0.858 to -0.901). Multivariate linear regression analysis found the strongest correlation with the value of LVEF at pentraxin 3 and adiponectin. Subsequent ROC-analysis confirmed the diagnostic value of adiponectin in patients with heart failure and preserved ejection fraction. Thus, the level of adiponectin more than 8.3 ng/ml served as a prognostic factor for the presence of heart failure in patients with LVEF >50% with a sensitivity of 94.3% and a specificity of 92.9% (area under the curve 0.977; 95% confidence interval from 0.954 to 0.999; p<0.001).. Among the 6 studied biomarkers of myocardial stress and inflammation only adiponectin has diagnostic significance in patients with heart failure and preserved ejection fraction.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Proteins; Chronic Disease; Cross-Sectional Studies; Echocardiography; Female; Galectin 3; Galectins; Growth Differentiation Factor 15; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Stroke Volume; Ventricular Function, Left

to determine levels of galectin-3, markers of renal dysfunction, and plasma oxidative stress; to assess their correlation in patients with chronic heart failure (CHF) of various severity.. We included in this study 157 CHF patients (with documented prior myocardial infarction. Patients were divided into 3 groups according to their NYHA functional class (group 1 - class II n=60, group 2 - class III n=52, group 3 - class IV n=45). All patients underwent clinical examination, echocardiography. Laboratory parameters included measurement of plasma levels of galectin-3, NT-proBNP, as well as markers of oxidative stress (oxidized low density lipoprotein cholesterol [oxLDLC], SH-groups) and renal dysfunction (creatinine, uric acid, cystatin-C).. The level of galectin-3 (median) in groups 1, 2, and 3 was 10, 19 and 38 ng/ml respectively. There were significant differences between groups (p<0,001). In all groups levels of galectin-3 significantly (p<0.01) correlated with those of oxLDL (positively) and SH-groups (negatively): r1=0.52, r2=0.59, r3=0.63, p<0.01, and r1=-0.58, r2=-0.65, r3=-0.71, respectively. Correlation analysis also revealed close and moderate correlations between galectin-3 and cystatin-C, glomerular filtration rate, and uric acid.. In patients with CHF and prior myocardial infarction plasma concentration of galectin-3 was associated with severity of CHF and significantly correlated with markers of renal dysfunction and plasma oxidative stress.

Topics: Biomarkers; Blood Proteins; Chronic Disease; Echocardiography; Female; Galectin 3; Galectins; Glomerular Filtration Rate; Heart Failure; Humans; Lipoproteins, LDL; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments

This study sought to determine the relationship between growth differentiation factor (GDF)-15 and clinical outcomes in ambulatory patients with heart failure and reduced ejection fraction (HFrEF).. The prognostic utility of GDF-15, a member of the transforming growth factor-β cytokine family, among patients with HF is unclear.. We assessed GDF-15 levels in 910 patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial, a randomized clinical trial of exercise training in patients with HFrEF. Median follow-up was 30 months. Cox proportional hazard models assessed the relationships between GDF-15 and clinical outcomes.. The median GDF-15 concentration was 1,596 pg/ml. Patients in the highest tertile of GDF-15 were older and had measurements of more severe HF (higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentrations and lower peak oxygen uptake on cardiopulmonary exercise testing [CPX]). GDF-15 therapy was a significant predictor of all-cause death (unadjusted hazard ratio [HR]: 2.03 when GDF-15 was doubled; p < 0.0001). This association persisted after adjustment for demographic and clinical and biomarkers including high sensitivity troponin T (hs-TnT) and NT-proBNP (HR: 1.30 per doubling of GDF-15; p = 0.029). GDF-15 did not improve discrimination (as measured by changes in c-statistics and the integrated discrimination improvement) in addition to baseline variables, including hs-TnT and NT-proBNP or variables found in CPX testing.. In demographically diverse, well-managed patients with HFrEF, GDF-15 therapy provided independent prognostic information in addition to established predictors of outcomes. These data support a possible role for GDF-15 in the risk stratification of patients with chronic HFrEF. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437).

Topics: Adult; Aged; Chronic Disease; Exercise Therapy; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke Volume

Acute coronary syndrome remains a significant problem for cardiologists. Despite improved therapy, mortality remains extremely high once CHF becomes symptomatic. Multimarker approach in cardiovascular risk prediction was proved as the most effective tool. One of the promising biomarkers is a stress-induced marker growth differentiation factor 15 (GDF-15). Purpose of the study was to improve stratification methods of CHF progression risk as a complication of ACS by studying levels of GDF-15. In our study we showed association between high level of GDF-15, determined at the first 24 hours after ACS, and CHF progression after 12 months.

Topics: Acute Coronary Syndrome; Biomarkers; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Growth Differentiation Factor 15; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; ST Elevation Myocardial Infarction

To describe adherence to international guidelines for chronic heart failure (CHF) management concerning diagnostics, pharmacological treatment and self-care behaviour in primary health care.. A cross-sectional descriptive study of patients with CHF, using data obtained from medical records and a postal questionnaire.. Three primary health care centres in Sweden.. Patients with a CHF diagnosis registered in their medical record.. Adherence to recommended diagnostic tests and pharmacological treatment by the European Society of Cardiology guidelines and self-care behaviour, using the European Heart Failure Self-care Behaviour Scale (EHFScBS-9).. The 155 participating patients had a mean age of 79 (SD9) years and 89 (57%) were male. An ECG was performed in all participants, 135 (87%) had their NT-proBNP measured, and 127 (82%) had transthoracic echocardiography performed. An inhibitor of the renin angiotensin system (RAS) was prescribed in 120 (78%) patients, however only 45 (29%) in target dose. More men than women were prescribed RAS-inhibition. Beta blockers (BBs) were prescribed in 117 (76%) patients, with 28 (18%) at target dose. Mineralocorticoidreceptor antagonists were prescribed in 54 (35%) patients and daily diuretics in 96 (62%). The recommended combination of RAS-inhibitors and BBs was prescribed to 92 (59%), but only 14 (9%) at target dose. The mean score on the EHFScBS-9 was 29 (SD 6) with the lowest adherence to daily weighing and consulting behaviour.. Adherence to guidelines has improved since prior studies but is still suboptimal particularly with regards to medication dosage. There is also room for improvement in patient education and self-care behaviour.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiology; Cardiovascular Agents; Chronic Disease; Cross-Sectional Studies; Diuretics; Echocardiography; Female; Guideline Adherence; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Primary Health Care; Self Care; Surveys and Questionnaires; Sweden

The circulating concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) has been shown to be a diagnostic tool for the detection of heart failure. Several factors influence NT-proBNP levels including age, sex, and body mass index (BMI). Therefore, the diagnostic sensitivity of NT-proBNP level for heart failure is relatively higher, but its specificity is low. This study aims to improve the diagnostic accuracy rate of this test by including multiple variables in the diagnostic test.The suspected chronic heart failure outpatients were divided into heart failure with reduced ejection fraction, heart failure with mid-range ejection fraction, heart failure with preserved ejection fraction, and normal heart function groups. Area under the receiver-operating characteristic (ROC) curve, cut-off value, and logistic regression analysis were used to select the model variables, sensitivity and specificity.In all, 436 subjects enrolled into this study were divided in 2 groups: model establishment (n = 300) and model validation (n = 136). In the model establishment group, the area under the curve (AUC) and cut-off value of NT-proBNP was 0.926 and 257.4 pg/mL, respectively. When age, glomerular filtration rate, BMI, atrial fibrillation, and sex were entered into the diagnosis model, AUC, sensitivity, and specificity further increased to 0.955 (95% confidence interval [CI] 0.934, 0.976), 94.2% (from 93.0%), and 86.7% (from 74.2%). The ROC curve of corrected NT-proBNP diagnostic formula for heart failure was also significantly higher (P = .037).The corrected NT-proBNP diagnostic formula was found to improve the diagnostic accuracy of chronic heart failure.

Topics: Age Factors; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; China; Chronic Disease; Databases, Factual; Diagnostic Tests, Routine; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Risk Assessment; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Sex Factors

Since the approval of sacubitril-valsartan for the treatment of chronic heart failure with reduced ejection fraction, a commonly raised suspicion is that a wider clinical use of this new drug may diminish the clinical utility of B-type natriuretic peptide testing as sacubitril may interfere with B-type natriuretic peptide clearance. In this education paper we critically assess this hypothesis based on the pathophysiology of the natriuretic peptide system and the limited published data on the effects of neprilysin inhibition on natriuretic peptide plasma concentrations in humans. As the main clinical application of B-type natriuretic peptide testing in acute cardiac care is and will be the rapid rule-out of suspected acute heart failure there is no significant impairment to be expected for B-type natriuretic peptide testing in the acute setting. However, monitoring of chronic heart failure patients on sacubitril-valsartan treatment with B-type natriuretic peptide testing may be impaired. In contrast to N-terminal-proBNP, the current concept that the lower the B-type natriuretic peptide result in chronic heart failure patients, the better the prognosis during treatment monitoring, may no longer be true.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Chronic Disease; Drug Combinations; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptides; Neprilysin; Peptide Fragments; Predictive Value of Tests; Stroke Volume; Tetrazoles; Valsartan

Frequent hospital admissions and reduced quality of life are the main complications of heart failure (HF). Plasma B-type natriuretic peptide (BNP) levels have been considered as a cost-effective method of screening for left ventricular dys-function. Studies regarding BNP-guided therapy revealed reduction in death or hospital stay for HF.. As saliva has fewer limitations than blood in regard to sampling, the aim of the present study was to test if salivary BNP concentration might be a new biomarker in patients with chronic HF.. This pilot study involved 35 admitted patients with decompensated HF diagnosis and 35 HF patients who had come for a check-up at the Department of Cardiology. The control group consisted of 25 people with no history of cardiac events. Saliva and plasma samples of all the participants were collected.. Mean plasma NT-proBNP was found at higher levels in admitted HF patients compared to outpatient HF (9.37 vs. 6.62 pg/mL, p < 0.001) and control groups (9.37 vs. 4.69 pg/mL, p < 0.001). Also, mean salivary BNP levels were higher in admitted patients with HF (6.50 ng/L, p < 0.001); and outpatient HF group (5.87 ng/L, p = 0.02) compared to the control group (5.64 ng/L).. Our study demonstrated that BNP could be detected in saliva and that the level is higher in HF patients, especially symptomatic ones. This means that salivary BNP may be useful in the diagnosis and follow-up for patients with HF, especially in emergency settings.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Saliva; Sensitivity and Specificity

We investigated a correlation between electromechanical properties of the myocardium and response to CD34+ cell therapy in patients with chronic heart failure.. We enrolled 40 patients with ischemic cardiomyopathy (ICM) and 40 with nonischemic dilated cardiomyopathy (DCM). All patients were in New York Heart Association functional class III and had a left ventricular ejection fraction (LVEF) <40%. CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Electroanatomic mapping was performed to define areas of myocardial scar and hibernation, and CD34+ cells were injected transendocardially in the hibernating areas. Patient were followed for 6 months; responders were defined as patients with LVEF increase of >5%. At baseline, the groups did not differ in sex, LVEF, creatinine, N-terminal pro-B-type natriuretic peptide or electroanatomic parameters (scar area: 53 ± 18% in ICM vs 55 ± 23% in DCM [P = .83]; hibernating area: 23 ± 13% vs 22 ± 12% [P = .56]). At 6 months we found similar rates of responders in both groups (60% in ICM vs 65% in DCM [P = .95]). When compared with nonresponders, responders had less myocardial scar (47 ± 17% vs 58 ± 15% [P = .003]).. In patients with chronic heart failure due to ICM and DCM we observed similar electroanatomic properties of the myocardium. In both groups, lower myocardial scar burden was associated with better clinical response to CD34+ cell therapy.

Topics: Adult; Aged; Analysis of Variance; Antigens, CD34; Cardiomyopathy, Dilated; Cell- and Tissue-Based Therapy; Chronic Disease; Echocardiography; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Imaging, Three-Dimensional; Injections, Intralesional; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Stroke Volume; Survival Rate; Time Factors; Treatment Outcome; Ventricular Remodeling

Biomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.. The biological variability of established biomarkers [NT-proBNP and high-sensitivity troponin T (hsTnT)], novel biomarkers [galectin-3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF-15)], and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CV. Biological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT-proBNP and GDF-15 have substantial variation, with lower variation for ST2, hsTnT, and galectin-3. These data are instrumental in proper interpretation of biomarker levels in HF patients.

Topics: Adult; Aged; Aldosterone; Biomarkers; Case-Control Studies; Chronic Disease; Creatinine; Female; Galectin 3; Growth Differentiation Factor 15; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Parathyroid Hormone; Peptide Fragments; Phosphates; Renin; Stroke Volume; Troponin T

Drug-induced cardiomyopathy can be life-threatening in patients with cancer. Our objective was to explore early detection of drug-induced cardiomyopathy in children with cancer. We enrolled pediatric outpatients diagnosed with cancer between 2012 and 2013. In addition, we recruited pediatric outpatients in good general condition without cardiac disease or cancer, as controls. We measured the serum levels of biomarkers and performed chest radiography, electrocardiography, and ultrasound cardiography (UCG). We analyzed left ventricular (LV) torsion and torsion-related parameters using 2-dimensional (2D) speckle tracking on UCG. In total, 35 pediatric patients were enrolled. All patients showed negative findings for plasma troponin T, radiography, and electrocardiography. During 2D speckle tracking, 9 patients were excluded due to inappropriate dynamic echo images. We compared UCG findings between 26 patients and 16 controls. Although there was no difference in ejection fraction between patients and controls, peak LV torsion tended to be lower in patients than in controls, and the absolute basal rotation value at the timing of peak LV torsion was significantly lower in patients than in controls. In conclusion, a decrease of basal rotation in 2D speckle tracking might indicate the initial changes leading to myocardial disorder after chemotherapy.

Topics: Adolescent; Anthracyclines; Antineoplastic Agents; Biomarkers; Bone Marrow Transplantation; Cardiomyopathies; Child; Chronic Disease; Cyclophosphamide; Early Diagnosis; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Maintenance Chemotherapy; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Radiography, Thoracic; Rotation; Stroke Volume; Troponin T

Topics: Ambulatory Care; Biomarkers; Chronic Disease; Forecasting; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Risk Assessment; Survival Analysis

Topics: Blood Gas Analysis; Carbon Dioxide; Cardiac Catheterization; China; Chronic Disease; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Respiratory Function Tests; Severity of Illness Index; Thromboembolism

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Several registries have described patients hospitalized with heart failure (HF), but only few looked at outpatients in the ambulatory setting mostly without long-term follow-up. We sought to determine the clinical characteristics, management, and 1-year outcomes of patients with chronic HF in Saudi Arabia.. Part of a prospective multicenter nationwide registry; HEart function Assessment Registry Trial in Saudi Arabia (HEARTS) and included chronic HF patients referred to four HFCs between September 2009 and December 2011.. We enrolled 685 patients with mean age 55.66±15.97years, 70.1% were men and 96.1% were Saudis. The main etiologies of HF were CAD (38.8%), dilated cardiomyopathy (36.5%), and hypertension (10.5%). Severe left ventricular dysfunction was present in 70.6% and median NT-proBNP was 2934.37pg/ml. The prescription rates of evidence based therapies (EBTs) before admission to HFC, at discharge from 1st clinic visit, and at 1-year follow up were 90%, 91% and 94% for beta-blockers, 79%, 80%, and 86% for ACEi/ARBs and 44%, 45%, and 42% for aldosterone antagonists; respectively. ICD was inserted in 21.9% and CRT in 6.6% at enrollment and increased to 29.1% and 8.8% after one year respectively. The all-cause mortality rate at 1year was 9% and 93.7% of which was cardiac-related. The all-cause one-year hospitalization rate was 39% and the total emergency room visit rate was 50%.. Chronic HF patients in Saudi Arabia are younger, commonly have severe LV systolic dysfunction and have relatively high annual mortality and re-hospitalization rates.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Hypertension; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Natriuretic Peptide, Brain; Outcome and Process Assessment, Health Care; Peptide Fragments; Registries; Saudi Arabia; Severity of Illness Index; Symptom Assessment; Ventricular Dysfunction, Left

To examine the changes in serum chromogranin A (CgA) and urotensin II (U II) levels in children with chronic heart failure (CHF) and their clinical significance.. A total of 58 children with CHF, among whom 17 had endocardial fibroelastosis (EFE) and 41 had dilated cardiomyopathy (DCM), were selected as CHF group, and 20 healthy children were selected as control group. Serum levels of CgA and U II were measured using enzyme-linked immunosorbent assay, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined by bi-directional lateral flow immunoassay. Ventricular remodeling indices were measured using echocardiography. The correlation between serum CgA and U II levels and ventricular remodeling was evaluated by Pearson correlation or Spearman's rank correlation analysis.. There were no significant differences in serum CgA and NT-proBNP levels between children with grade II heart function and the control group (P>0.05). However, the serum CgA and NT-proBNP levels gradually increased as the heart function grade increased, and were significantly higher in grade III and IV children compared to those in the control group (P<0.05). U II levels were lower in children with grade II, III, or IV heart function than those in the control group (P<0.05), and significantly decreased with the aggravation of CHF (P<0.05). There were no significant differences in CgA and U II levels between patients with EFE and DCM (P>0.05). Serum CgA concentration was positively correlated with left ventricular mass index (LVMI), NT-proBNP, and cardiac function classification (r=0.279, 0.649, and 0.778 respectively; P<0.05), but was negatively correlated with left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and U II (r=-0.369, -0.322, and -0.718 respectively; P<0.05). Serum U II concentration was negatively correlated with NT-proBNP and cardiac function classification (r=-0.472 and -0.591 respectively; P<0.05), but was not correlated with LVMI, LVEF, and LVFS (P>0.05).. CgA may play a role in ventricular remodeling in children with CHF. Serum CgA and U II may serve as a reference for the diagnosis and functional classification of heart failure.

Topics: Cardiomyopathy, Dilated; Child; Child, Preschool; Chromogranin A; Chronic Disease; Endocardial Fibroelastosis; Female; Heart Failure; Humans; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Urotensins; Ventricular Function, Left

Objective To evaluate the criterion validity of Chronic Heart Failure (CHF) -Quality of Life (QOL) Scale of Integrative Medicine (abbreviated as Scale). Methods Clinical data of 249 CHF in- patients were collected. Using Pearson and Spearman correlation analyses, the indicators such as NT- proBNP, cardiac function classification (NYHA) , 6 Minutes Walk Test (6MWT) , left ventricular ejection fraction (LVEF) were taken as exterior contrasts of standard validity, the correlation between the Scale and physicochemical indices of modern medicine were analyzed. The standard validity of the Scale was evaluated. Results Compared with before treatment, the numerical value of the overall index score of the Scale, LVEF, LVEF≤40%, and 6MWT all increased (P <0. 05, P <0. 01) ; NT-proBNP level decreased (P <0. 01). The numerical value of the overall index score of the Scale was negatively correlated with NY- HA classification and NT-proBNP level, but positively correlated with LVEF and 6MWT, all with statistical difference (P <0. 01). NT-proBNP, 6MWT, and NYHA classification were all correlated with the scores of the Scale in each field (P <0. 05). LVEF was correlated with the scores of the Scale in each field (P < 0. 05) except social function. Conclusion The Scale had favorable criterion validity, which could be taken as an indicator for comprehensive curative effect evaluation system of CHF.

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Integrative Medicine; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Ventricular Function, Left

The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT).. The qualitative blood counts and the serum levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy controls were analysed prospectively in this observational study. The 2-year mortality was considered as primary endpoint and the 6-month reverse remodelling (≥15% decrease in the end-systolic volume) as secondary endpoint. Multivariable regression analyses were applied and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. The NL ratio was elevated in chronic heart failure patients when compared with the healthy controls [2.93 (2.12-4.05) vs. 2.21 (1.64-2.81), P < 0.0001]. The baseline NL ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n = 63, odds ratio = 0.38 (0.17-0.85), P = 0.01; NRI = 0.49 (0.14-0.83), P = 0.005; IDI = 0.04 (0.00-0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio = 2.44 (1.04-5.71), P = 0.03; NRI = 0.63 (0.24-1.01), P = 0.001; IDI = 0.04 (0.00-0.08), P = 0.02] independently of the NT-proBNP levels or other factors.. The NL ratio is elevated in chronic heart failure and predicts outcome after CRT. According to the reclassification analysis, 4% of the patients would have been better categorized in the prediction models by combining the NT-proBNP with the NL ratio. Thus, a single blood count measurement could facilitate the optimal patient selection for the CRT.

Topics: Aged; Biomarkers; Cardiac Resynchronization Therapy; Case-Control Studies; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Hungary; Logistic Models; Lymphocyte Count; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neutrophils; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies

Surviving pulmonary embolism (PE) brings a risk of thromboembolic disease chronicity. Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a result of one or multiple pulmonary embolic events. It is an incapacitating long-term complication of thromboembolic disease with a negative impact on the patient's quality of life and prognosis. Contemporary pharmacological and especially surgical treatment possibilities offer hope for the patient's full recovery, but an early diagnosis is crucial for success.. In a prospective study cohort of 97 consecutive patients with a proven diagnosis of PE as the first documented thromboembolic event we tried to estimate the incidence of CTEPH during a 2-year follow-up.. Four individuals from our study population developed CTEPH, which represents an incidence of 4.2%.. Chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors is a not uncommon complication deserving the attention of clinicians. Patients at risk of CTEPH can be identified for effective follow-up according to echocardiographic finding of elevated pulmonary artery systolic pressure and NT-proBNP levels at the time of hospital discharge.

Topics: Chronic Disease; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Thromboembolism

Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline.. Heart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23-0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23-1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28-36%; P<0.001), NT-proBNP (2771-1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11-0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16-0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients.. Left bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome.

Topics: Action Potentials; Aged; Biomarkers; Bundle-Branch Block; Cardiac Resynchronization Therapy; Chronic Disease; Disease-Free Survival; Echocardiography; Electrocardiography; Female; Heart Conduction System; Heart Failure; Heart Ventricles; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Recovery of Function; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Function, Right

Urinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF.. In a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([(131) I]hippuran clearance) and measured glomerular filtration rate (GFR; [(125) I]iothalamate)} and urinary tubular damage markers. The association between plasma KIM-1, plasma creatinine, and clinical outcome was further explored in a cohort of 2033 acute HF patients. Median plasma KIM-1 was 171.5 pg/mL (122.8-325.7) in chronic (n = 99) and 295.1 pg/mL (182.2-484.2) in acute HF (n = 1588). In chronic HF, plasma KIM-1 was associated with GFR (P < 0.001), creatinine, and cystatin C. Plasma KIM-1 was associated with urinary N-acetyl-β-d-glucosaminidase (NAG), but not with other urinary tubular damage markers. Log plasma KIM-1 predicted adverse clinical outcome after adjustment for age, gender, and GFR [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.07-3.53, P = 0.030]. Statistical significance was lost after correction for NT-proBNP (HR 1.61, 95% CI 0.81-3.20, P = 0.175). In acute HF, higher plasma KIM-1 levels were associated with higher creatinine, lower albumin, and presence of diabetes. Log plasma KIM-1 predicted 60-day HF rehospitalization (HR 1.27, 95% CI 1.03-1.55, P = 0.024), but not 180-day mortality or 60-day death or renal or cardiovascular rehospitalization.. Plasma KIM-1 is associated with glomerular filtration and urinary NAG, but not with other urinary tubular damage markers. Plasma KIM-1 does not predict outcome in chronic HF after correction for NT-proBNP. In acute HF, plasma KIM-1 predicts HF rehospitalization in multivariable analysis.

Topics: Acetylglucosaminidase; Acute Disease; Adult; Aged; Chronic Disease; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Kidney Tubules; Lipocalin-2; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Circulation; Serum Albumin

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Limit of Detection; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values

This study sought to observe the effects of allopurinol on the cardiac function of non-hyperuricaemic patients with chronic heart failure and determine the safety of allopurinol for clinical applications.. A group of 125 consecutive cases of non-hyperuricaemic patients with chronic heart failure who were treated at Chongqing Emergency Medical Centre between July 2011 and June 2012 were enrolled and were randomly divided into allopurinol (300 mg/day) group (n=62) and control group (n=63). During the six months treatment period, levels of cardiac function, brachial artery endothelial function, inflammatory cytokines, and biochemical markers were routinely examined.. After three months of allopurinol treatment, patients exhibited an increase in flow-mediated vasodilatation (FMD) of brachial artery, whereas, after six months of treatment, the cardiac function classification was improved; plasma levels of brain natriuretic peptide and tumour necrosis factor-a were decreased; left ventricular internal diameter was diminished; and the ejection fraction was increased (p<0.01 for all the parameters) in patients. Serum uric acid level was decreased during the treatment period for both groups, with no significant difference between the two groups. Liver and kidney dysfunction was not observed among the study participants, and no significant increase in creatine kinase level was detected for either treatment group.. For non-hyperuricaemic patients with chronic heart failure, the addition of six months of allopurinol therapy was safe and effective. Moreover, in these patients, allopurinol treatment not only can significantly ameliorate the left ventricular function and reduce the level of inflammatory factors but could also improve endothelial function.

Topics: Adult; Aged; Allopurinol; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Hyperuricemia; Male; Middle Aged; Natriuretic Peptide, Brain; Uric Acid; Vasodilation; Ventricular Function, Left

The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure.. A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient <20 mmHg) showed a worse outcome [hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.12-5.00, P = 0.02]. RV dysfunction [tricuspid annular plane systolic excursion (TAPSE) ≤14 mm] in the presence of a low TR gradient identified patients at higher risk of events (HR 2.97, 95% CI 1.19-7.41, P = 0.02). Multivariate analysis showed as best predictors of outcome low RV contraction pressure index (RVCPI), defined as TAPSE × TR gradient, and high estimated right atrial pressure (eRAP). Adding RVCPI (<400 mm*mmHg) and eRAP (≥20 mmHg) to conventional clinical (ADHERE risk tree and NT-proBNP) and echocardiographic risk evaluation resulted in an increase in net reclassification improvement of +19.1% and +20.1%, respectively (P = 0.01) and in c-statistic from 0.59 to 0.73 (P < 0.01).. In acute decompensation of advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI.

Topics: Aged; Cardiovascular Diseases; Chronic Disease; Echocardiography; Emergencies; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Ventricular Dysfunction, Right

Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH.. Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA.. 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH.. This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA.

Topics: Aged; Arterial Pressure; Biomarkers; Chronic Disease; Cohort Studies; Endarterectomy; Female; Glycated Hemoglobin; Hemodynamics; Humans; Hypertension, Pulmonary; Immunoassay; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Pulmonary Artery

Topics: Chronic Disease; Defibrillators, Implantable; Electric Impedance; Heart Failure; Humans; Natriuretic Peptide, Brain

We have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants.. The study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50-74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample.. Clinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare.. We will continue following this patients' cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities.. NCT02646943; Pre-results.

Topics: Aged; Biomarkers; Brazil; Chagas Cardiomyopathy; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Immunosuppressive Agents; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Nitroimidazoles; Peptide Fragments; Population Surveillance; Predictive Value of Tests; Prognosis; Prospective Studies; Quality of Life; Socioeconomic Factors

The aim of this study was to determine the prognostic value of plasma corin in patients with chronic heart failure (CHF).. In recent years, accumulating evidence has indicated that corin plays a critical role in regulating blood pressure and cardiac function.. We enrolled 1,148 consecutive CHF patients in a prospective cohort study and explored the association between plasma corin levels and clinical prognosis using multivariate Cox regression analysis.. Patients with low corin levels (<458 pg/ml) were more likely to be women and to be hypertensive. Low corin was found to be associated with an increase in New York Heart Association (NYHA) functional class and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and a decrease in left ventricular ejection fraction (LVEF) and the estimated glomerular filtration rate (eGFR). Multivariate Cox regression analysis suggested that log corin was an independent predictor of major adverse cardiac event(s) (MACE) (hazard ratio: 0.62; 95% confidence interval: 0.39 to 0.95), together with age, diabetes, NYHA functional class, LVEF, eGFR, and log NT-proBNP. In addition, log corin was also a significant predictor for cardiovascular death (p = 0.041) and heart failure rehospitalization (p = 0.015) after adjustment for clinical variables and established biomarkers of adverse prognosis. The Kaplan-Meier survival curves showed that low corin was a significant predictor of MACE in patients with NT-proBNP levels above and below the median.. Our study demonstrates that plasma corin is a valuable prognostic marker of MACE in patients with CHF, independent of established conventional risk factors.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Disease Progression; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Serine Endopeptidases; Stroke Volume

Soluble ST2 (sST2) is a novel biomarker implicated in myocardial remodeling and fibrosis. Recent studies in normal subjects have suggested that the biologic variability (BV) of sST2 is significantly lower than that of the B-type natriuretic peptides and N-terminal pro B-type natriuretic peptide (NTproBNP). It may, consequently, be a better biomarker for monitoring patients with chronic heart failure (CHF). To date, no published studies have examined the BV of sST2 in a heart failure population. Blood samples from 50 outpatients with pharmacologically optimized stable CHF and persistent left ventricular dysfunction (ejection fraction <40%) were collected at baseline, 1 hour, 1 month, 3 months, and 6 months. Using log-transformed data, mean intra-individual coefficients of variation (CVI) and subsequent reference change values were calculated for both NTproBNP and sST2. Results demonstrate significantly lower CVI and reference change values for sST2 compared with NTproBNP at 1 month (12.02 [36%] vs 36.75 [103%]), p <0.001, 3 months (12.23 [36%] vs 40.98 [114%]), p <0.001, and 6 months (16.41 [47%] vs 46.02 [128%]), p <0.001. In conclusion, the BV of sST2 is significantly lower than that of NTproBNP in patients with CHF. These results support previous indications that sST2 may be a better biomarker for monitoring such patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cohort Studies; Female; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Time Factors

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and -dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

Topics: Adrenergic beta-Agonists; Animals; Chronic Disease; Collagen Type I; Coronary Vessels; Heart; Heart Failure; Heart Ventricles; Isoproterenol; Kidney Cortex; Ligation; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Norepinephrine; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-1; Receptors, Adrenergic, beta-2; Renal Artery; Sodium; Sympathectomy

Natriuretic peptides play an important role in the diagnosis and risk stratification of patients with acute and chronic heart failure. Multiple studies have shown that these peptides are liable to the influence of individual factors. For N-terminal-pro-B-type natriuretic peptide (NT-proBNP) some of these confounding factors have been evaluated over the years such as age, gender, New York Heart Association (NYHA) class and body mass index (BMI). The aim of this study was to establish confounding factors of mid-regional pro-atrial natriuretic peptide (MR-proANP) assessment.. We studied 684 patients (94% male, age 61.2±11.2, left ventricular ejection fraction [LVEF]<35%-45%, NYHA class (I/II/III/IV: 8.4/45.8/39.5/6.3%), ischaemic aetiology 71%, body mass index [BMI] 26.5±4.3kg/m(2), mean MR-proANP 296.0±281.0pmol/L, mean NT-proBNP 2792.0±5328.6pg/mL, mean creatinine level 110.2±38.0μmol/L and mean haemoglobin 13.9±1.5g/dL) with clinically stable chronic heart failure. MR-proANP levels increased with increasing NYHA class (p<0.0001) and an increasing BMI category was associated with decreasing values of MR-proANP (p<0.0001). We found MR-proANP to be independently associated with BMI, creatinine, ischaemic aetiology, LVEF and NYHA class. Meanwhile, NT-proBNP was independently associated with BMI, creatinine, haemoglobin, LVEF and NYHA class.. MR-proANP is subject to the almost identical influencing factors like NT-proBNP. The effects of anaemia warrant further study.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cohort Studies; Confounding Factors, Epidemiologic; Female; Heart Failure; Humans; Internationality; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

BACKGROUND This retrospective study was performed to evaluate the value of baseline red blood cell distribution width (RDW) for predicting the severity of chronic heart failure (CHF) compared with N-terminal prohormone brain natriuretic peptide (NT-ProBNP) and other hematological and biochemical parameters. MATERIAL AND METHODS Hematological and biochemical parameters were obtained from 179 patients with New York Heart Association (NYHA) CHF class I (n=44), II (n=39), III (n=41), and IV (n=55). Receiver operator characteristic (ROC) curves were used for assessing predictive values. RESULTS RDW increased significantly in class III and IV compared with class I (14.3±2.3% and 14.3±1.7% vs. 12.9±0.8%, P<0.01). Areas under ROCs (AUCs) of RDW and NT-ProBNP for class IV HF were 0.817 and 0.840, respectively. RDW was markedly elevated in the mortality group compared with the survival group (13.7±1.7 vs. 15.8±1.8, P<0.01). The predictive value of RDW was lower than that of NT-ProBNP but was comparable to white blood cell (WBC), neutrophil (NEU), lymphocyte (L), and neutrophil/lymphocyte ratio (N/L) for mortality during hospitalization, with AUCs of 0.837, 0.939, 0.858, 0.891, 0.885, and 0.885, respectively. RDW and NT-proBNP showed low predictive values for repeated admission (≥3). RDW was an independent risk factor for mortality (OR=2.531, 95% CI: 1.371-4.671). CONCLUSIONS RDW increased significantly in class III and IV patients and in the mortality group. The predictive value of RDW is comparable to NT-proBNP for class IV and lower than that of NT-proBNP for mortality. Elevated RDW is an independent risk factor for mortality.

Topics: Adult; Aged; Chronic Disease; Erythrocyte Count; Erythrocyte Indices; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; ROC Curve

Galectin-3 demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcome in heart failure (HF) patients. The objective of this study was to analyze the value of a predischarged determination of plasma galectin-3 alone and with plasma brain natriuretic peptide (BNP) in predicting mid-term outcome in frequent-flyers (FF) HF (≥2 hospitalization for HF/year)/dead patients discharged after an acute decompensated HF (ADHF) episode.All FF chronic HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-minute walk test, and an echocardiogram within 48 hours upon hospital discharge. Death by any cause, cardiac transplantation, and worsening HF requiring readmission to hospital were considered cardiovascular events.Eighty-three patients (67 males, age 73.2 ± 8.6 years old) were analyzed (mean follow-up 11.6 ± 5.2 months; range 4-22 months). During the follow-up 38 events (45.7%) were scheduled: (13 cardiac deaths, 35 rehospitalizations for ADHF). According to medical history, in 33 patients (39.8%) a definition of FF HF patients was performed (range 2-4 hospitalization/year). HF patients who suffered an event (FF or death) demonstrated more impaired ventricular function (P = 0.037), higher plasma BNP (P = 0.005), and Gal-3 at predischarge evaluation (P = 0.027). Choosing adequate cut-off points (BNP ≥ 500 pg/mL and Gal-3 ≥ 17.6 ng/mL), the Kaplan-Meier curves depicted the powerful stratification using BNP + Gal-3 in predicting clinical course at mid-term follow-up (log rank 5.65; P = 0.017).Adding Gal-3 to BNP, a single predischarge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode.

Topics: Aged; Chronic Disease; Female; Galectin 3; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Patient Discharge; Predictive Value of Tests; Prognosis

Chronic heart failure (CHF) has been shown to be associated with an increased incidence of sleep-disordered breathing. Whether treatment with noninvasivepositive-pressure ventilation (NPPV), including continuous positive airway pressure, bi-level positive airway pressure and adaptive servo-ventilation, improves clinical outcomes of CHF patients is still debated. 2,832 CHF patients were enrolled in our analysis. NPPV was significantly associated with improvement in left ventricular ejection fraction (39.39% vs. 34.24%; WMD, 5.06; 95% CI, 3.30-6.81; P < 0.00001) and plasma brain natriuretic peptide level (268.23 pg/ml vs. 455.55 pg/ml; WMD, -105.66; 95% CI, [-169.19]-[-42.13]; P = 0.001). However, NPPV did not reduce all-cause mortality (0.26% vs. 0.24%; OR, 1.13; 95% CI, 0.93-1.37; P = 0.22) or re-hospitalization rate (57.86% vs. 59.38%; OR, 0.47; 95% CI, 0.19-1.19; P = 0.02) as compared with conventional therapy. Despite no benefits on hard endpoints, NPPV may improve cardiac function of CHF patients. These data highlight the important role of NPPV in the therapy of CHF.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Noninvasive Ventilation; Odds Ratio; Patient Readmission; Prognosis; Quality of Life; Sample Size; Sleep Apnea Syndromes; Treatment Outcome; Ventricular Function, Left

To assess whether B-type natriuretic peptide (BNP) can serve as a predictor of end-stage chronic heart failure (CHF) in patients with severe systolic dysfunction of the systemic right ventricle (SRV).. We performed a retrospective analysis in 28 patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) who were evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. The primary endpoints of the study (end-stage CHF) were progressive CHF, urgent HTx, and ventricular assist device (VAD) implantation. Plasma BNP levels were measured using a chemiluminescent immunoassay.. During median follow-up of 29 months (interquartile range, 9-50), 3 patients died of progressive CHF, 5 patients required an urgent HTx, and 6 patients underwent VAD implantation. BNP was a strong predictor of end-stage CHF (hazard ratio per 100 ng/L: 1.079, 95% confidence interval, 1.042-1.117, P<0.001). The following variables with corresponding areas under the curve (AUC) were identified as the most significant predictors of end-stage CHF: BNP (AUC 1.00), New York Heart Association functional class class III or IV (AUC 0.98), decompensated CHF in the last year (AUC 0.96), and systolic dysfunction of the subpulmonal ventricle (AUC 0.96).. BNP is a powerful predictor of end-stage CHF in individuals with systolic dysfunction of the SRV.

Topics: Adult; Aged; Chronic Disease; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Retrospective Studies; Severity of Illness Index; Ventricular Dysfunction, Right

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.

Topics: Acute Disease; Adolescent; Biomarkers; Cardiomyopathy, Dilated; Child; Child, Preschool; Chronic Disease; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate

Topics: Aged; Aged, 80 and over; Alleles; Biomarkers; Chronic Disease; Comorbidity; Enzyme-Linked Immunosorbent Assay; Female; Genetic Predisposition to Disease; Genotype; Heart Failure; HLA-G Antigens; Humans; INDEL Mutation; Male; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Risk Factors; ROC Curve; Up-Regulation; Ventricular Dysfunction, Left

Chronic total occlusion percutaneous coronary intervention (CTO-PCI) can improve angina and left ventricular ejection fraction (LVEF). These benefits were not assessed in populations with heart failure with reduced ejection fraction (HFrEF). We studied the effect of CTO-PCI on left ventricular function and clinical parameters in patients with HFrEF.. Using cardiovascular magnetic resonance (CMR), we studied 29 patients with HFrEF and evidence of viability and/or ischemia in the territory supplied by a CTO who were successfully treated with CTO-PCI. In patients with multi-vessel disease, non-CTO PCI was also performed. Imaging parameters, clinical status, and brain natriuretic peptide (BNP) levels were evaluated before and 6 months after CTO-PCI.. A decrease in left ventricular end-systolic volume (160 ± 54 ml vs. 143 ± 58 ml; p = 0.029) and an increase in LVEF (31.3 ± 7.4 % vs. 37.7 ± 8 %; p < 0.001) were observed. There were no differences in LVEF improvement between patients who underwent non-CTO PCI (n = 11) and those without this intervention (n = 18); (p = 0.73). The number of segments showing perfusion defects was significantly reduced (0.5 ± 1 vs. 0.2 ± 0.5; p = 0.043). Angina (p = 0.002) and NYHA functional class (p = 0.004) improved, and BNP levels decreased (p = 0.004) after CTO-PCI.. In this group of patients with HFrEF showing CMR evidence of viability and/or ischemia within the territory supplied by the CTO, an improvement in ejection fraction, left ventricular end-systolic volume and ischemia burden was observed after CTO-PCI. Clinical and laboratory parameters also improved.. ClinicalTrials.gov NCT02570087 . Registered 6 October 2015.

Topics: Aged; Biomarkers; Chronic Disease; Contrast Media; Coronary Angiography; Coronary Occlusion; Female; Health Status; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organometallic Compounds; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Recovery of Function; Stroke Volume; Time Factors; Tissue Survival; Treatment Outcome; Ventricular Function, Left

The purpose in the present study was to compare prognostic risk factors between older and younger chronic heart failure (CHF) patients.. We examined 598 consecutive CHF patients (476 men and 122 women, mean age 61.4 ± 14.3 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination. We divided the 598 patients into two groups: the elderly group (age ≥75 years, n = 123) and the young group (age <75, n = 475). We compared blood testing data, exercise capacity, cardiac function and prognosis between the two groups. Patients were followed up (median 782 days) to register cardiac deaths or rehospitalization as a result of worsening heart failure.. Patients in the elderly group were associated with higher frequencies of atrial fibrillation and diuretic use than those in the young group. Patients in the elderly group had lower hemoglobin concentration, more impaired renal function, higher plasma B-type natriuretic peptide (BNP) levels, smaller left ventricular volume, longer deceleration time of early mitral wave and lower exercise capacity than those in the young group. There were 199 cardiac events during follow-up periods. As expected, Kaplan-Meier analysis showed that patients in the elderly group had higher cardiac event rates than those in the young group. In the young group, multivariable Cox hazard analysis showed that hemoglobin concentration, log BNP and peak VO(2) were independent predictors related to cardiac events. In contrast, in the elderly group, estimated glomerular filtration rate, atrial fibrillation and peak VO(2) were independent factors to predict adverse clinical outcomes.. Prognostic factors were different between the elderly and young patients in CHF.

Topics: Age Factors; Aged; Chronic Disease; Echocardiography, Doppler; Exercise Test; Exercise Tolerance; Female; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Prognosis; Risk Factors; Stroke Volume; Survival Analysis

We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin [HbA(1c)] on neurohormonal activation and outcome in chronic heart failure (CHF).. Nine hundred and twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles.. Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.

Topics: Aged; Biomarkers; Chronic Disease; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renin; Ventricular Dysfunction, Left

Adaptive servo-ventilation (ASV) therapy using an innovative ventilator-originally developed to treat sleep-disordered breathing (SDB)-is a novel modality of noninvasive positive pressure ventilation and is gaining acceptance among Japanese cardiologists in expectation of its applicability to treat patients with chronic heart failure (CHF) based on its acute beneficial hemodynamic effects. We conducted a multicenter, retrospective, real-world observational study in 115 Japanese patients with CHF, who had undergone home ASV therapy for the first time from January through December 2009, to examine their profile and the effects on their symptoms and hemodynamics. Medical records were used to investigate New York Heart Association (NYHA) class, echocardiographic parameters including left ventricular ejection fraction (LVEF), cardiothoracic ratio (CTR), brain natriuretic peptide (BNP), and other variables. Most of the patients were categorized to NYHA classes II (44.4 %) and III (40.7 %). SDB severity was not determined in 44 patients, and SDB was not detected or was mild in 27 patients. In at least 71 patients (61.7 %), therefore, ASV therapy was not applied for the treatment of SDB. CHF was more severe, i.e., greater NYHA class, lower LVEF, and higher CTR, in 87 ASV-continued patients (75.7 %) than in 28 ASV-discontinued patients (24.3 %). However, SDB severity was not related to continuity of ASV. The combined proportion of NYHA classes III and IV (P = 0.012) and LVEF (P = 0.009) improved significantly after ASV therapy. CTR and BNP did not improve significantly after ASV therapy but showed significant beneficial changes in their time-course analysis (P < 0.05, respectively). Improvements in LVEF and NYHA class after ASV therapy were not influenced by SDB severity at onset. The present study suggests that ASV therapy would improve the symptoms and hemodynamics of CHF patients, regardless of SDB severity. A randomized clinical study to verify these effects is warranted.

Topics: Aged; Body Weight; Chronic Disease; Echocardiography; Female; Heart Failure; Hemodynamics; Humans; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Positive-Pressure Respiration; Retrospective Studies; Severity of Illness Index; Sleep Apnea Syndromes; Treatment Outcome; Ventilators, Mechanical; Ventricular Function, Left

Acutely decompensated chronic heart failure (ADHF) is considered a life-threatening event. Despite contemporary treatment strategies of ADHF, frequent recurrent hospitalizations due to other cardiovascular reasons after discharge of patients from hospital occur. The objective of the study was to examine the prognostic value of circulating endothelial-derived apoptotic microparticles (EMPs) to mononuclear progenitor cells (MPCs) ratio for post-discharge patients with clinical stabilization after ischemic ADHF.. We consecutively enrolled 136 patients (62 male) with coronary artery disease (CAD) admitted with a primary diagnosis of ADHF. All patients gave written informed consent for participation in the study. At baseline, all enrolled patients were hemodynamically stable and they had New York Heart Association (NYHA) III/IV classes of ischemic chronic heart failure (CHF). Observation period started at discharge from the hospital and was up to 3 years. Flow cytometry analysis for quantifying the number of EMPs and angiogenic MPCs was used.. Calculated EMP to MPC ratios in survivor and dead patient cohort were 8.4 (95% CI=7.6-9.2) and 78.9 (95% CI=53.0-116.6), respectively (p=0.001). MPCs, EMPs, NYHA class, N-terminal pro-brain natriuretic peptide (NT-proBNP) and increased NT-proBNP>30% within 24-84h of admission period remained statistically significant for all-cause mortality, CHF-related death, and CHF-related rehospitalization, whereas left ventricular ejection fraction and high-sensitivity C-reactive protein for all variables did not. We found that the addition of EPMs to MPCs ratio to the ABC model (NT-pro-BNP, increased NT-pro-BNP>30%) improved the relative integrated discrimination indices by 19.6% for all-cause mortality, by 21.7% for CHF-related death, and by 19.5% for CHF-related rehospitalization.. We demonstrated that EMP to MPC ratio is considered an important indicator of an imbalance between angiogenic and apoptotic responses with possible relation to cardiovascular outcomes in post-discharge patients with clinical stabilization after ischemic ADHF.

Topics: Aged; Apoptosis; Biomarkers; Cell-Derived Microparticles; Chronic Disease; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Models, Cardiovascular; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Severity of Illness Index; Stem Cells

To determine the prevalence, clinical correlates and the effects on outcome of vitamin B12 and folic acid levels in patients with chronic heart failure (HF).. We studied an international pooled cohort comprising 610 patients with chronic HF. The main outcome measure was all-cause mortality.. Mean age of the patients was 68±12 years and median serum N-terminal prohormone brain natriuretic peptide level was 1801 pg/mL (IQR 705-4335). Thirteen per cent of the patients had an LVEF >45%. Vitamin B12 deficiency (serum level <200 pg/mL), folate deficiency (serum level <4.0 ng/mL) and iron deficiency (serum ferritin level <100 µg/L, or 100-299 µg/L with a transferrin saturation <20%) were present in 5%, 4% and 58% of the patients, respectively. No significant correlation between mean corpuscular volume and vitamin B12, folic acid or ferritin levels was observed. Lower folate levels were associated with an impaired health-related quality of life (p=0.029). During a median follow-up of 2.10 years (1.31-3.60 years), 254 subjects died. In multivariable proportional hazard models, vitamin B12 and folic acid levels were not associated with prognosis.. Vitamin B12 and folate deficiency are relatively rare in patients with chronic HF. Since no significant association was observed between mean corpuscular volume and neither vitamin B12 nor folic acid levels, this cellular index should be used with caution in the differential diagnosis of anaemia in patients with chronic HF. In contrast to iron deficiency, vitamin B12 and folic acid levels were not related to prognosis.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Chronic Disease; Erythrocyte Indices; Europe; Female; Ferritins; Folic Acid Deficiency; Heart Failure; Humans; Iron; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Proportional Hazards Models; Quality of Life; Risk Factors; Stroke Volume; Time Factors; Transferrin; Treatment Outcome; Ventricular Function, Left; Vitamin B 12; Vitamin B 12 Deficiency

Compared to patients without a collateral supply, long-term cardiac mortality is reduced in patients with well-developed coronary collateral circulation (CCC). Cardiovascular risk markers, such as N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP) and high-sensitive cardiac troponin T (hs-cTnT) are independent predictors for cardiovascular mortality.. The main goal of this study was to examine the relationship between CCC and cardiovascular risk markers.. We prospectively enrolled 427 stable coronary artery disease patients with chronic total occlusion (mean age: 57.5±11.1 years). The patients were divided into two groups, according to their Rentrop scores: (a) poorly developed CCC group (Rentrop 0 and 1) and (b) well-developed CCC group (Rentrop 2 and 3). NT-proBNP, hs-CRP, hs-cTnT, uric acid and other biochemical markers were also measured. The SYNTAX score was calculated for all patients.. The patients in the poorly developed CCC group had higher frequencies of diabetes and hypertension (p<0.05 for both). Compared to the well-developed CCC group, the SYNTAX score, Hs-cTnT, hs-CRP, NT-proBNP, uric acid, neutrophil count and mean platelet volume (MPV) values were higher in patients with poorly developed CCC (p<0.05 for all). On multivariate logistic regression analysis, hs-cTnT (β=0.658, 95% CI=0.589-0.735, p<0.001) and NT-proBNP (β=0.991, 95% CI=0.987-0.995, p<0.001) as well as hs-CRP and diabetes were independent predictors of CCC.. Cardiac risk markers, such as NT-proBNP, hs-cTnT and hs-CRP are independently associated with CCC in stable coronary artery disease with chronic total occlusion.

Topics: Aged; Biomarkers; C-Reactive Protein; Chronic Disease; Coronary Artery Disease; Coronary Circulation; Coronary Occlusion; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Troponin T

Cardiac troponin (cTn) levels offer prognostic information for patients with heart failure. Highly sensitive assays detect levels of cTn much lower than the 99th percentile of standard cTn assays. We hypothesize that cardiac troponin levels measured by a high-sensitivity assay provide better prognostic value compared with cTn levels measured by a standard assay in patients with chronic heart failure.. We measured high-sensitivity cTnT (hs-cTnT) and standard cardiac troponin I (cTnI) levels, as well as amino-terminal pro B-type natriuretic peptide (NT-proBNP) in 504 sequential stable patients with a history of heart failure who underwent elective coronary angiography, without acute coronary syndrome, and with 5-year follow-up of all-cause mortality.. The median hs-cTnT level was 21.2 (interquartile range 12.3-40.9) ng/L and 170 subjects died over 5 years. In a head-to-head overall comparison, hs-cTnT provided increased prognostic utility compared with cTnI (area under the curve [AUC] 66.1% and AUC 69.4%, respectively, P = .03; 9.0% integrated discrimination improvement, P < .001; and 13.6% event-specific reclassification, P < .001), and was independent of NT-proBNP and renal function. Even within the subset of patients where cTn levels by both assays were above the limit of quantification, higher hs-cTnT is associated with a 2-fold increase in 5-year mortality risk after adjusting for traditional risk factors (tertile 1 vs 3: hazard ratio [95% confidence interval] 2.0 [1.3-3.2]; P = .0002).. Cardiac troponin can be detected by the high-sensitivity assay in more patients with chronic heart failure than the standard assay, and may yield independent and better prognostic accuracy for mortality prediction than standard assay.

Topics: Aged; Area Under Curve; Chronic Disease; Confidence Intervals; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Ohio; Patient Acuity; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Sensitivity and Specificity; Troponin

The purpose of this study was to determine the prognostic significance and associated clinical profile of early post-discharge N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory among patients hospitalized for worsening chronic heart failure (HHF).. This post-hoc analysis of the Aliskiren Trial in Acute Heart Failure Outcomes (ASTRONAUT) included 1351 HHF patients with ejection fraction (EF) ≤40%, elevated B-type natriuretic peptide ≥400 pg/mL or NT-proBNP ≥1600 pg/mL at admission, and available NT-proBNP measurements (from a central core laboratory) at baseline (median 5 days after admission) and 1-month follow-up. The co-primary endpoints were all-cause mortality and cardiovascular mortality or HHF within 12 months. Median follow-up was 11.3 months. Patients with decreasing post-discharge NT-proBNP trajectory tended to be younger and have non-ischaemic HF aetiology. The presence of baseline atrial fibrillation was associated with high NT-proBNP at 1 month (i.e. above the median), regardless of the baseline value. After adjustment for patient characteristics and 1-month NT-proBNP level, every twofold increase in continuous NT-proBNP change from baseline to 1 month was predictive of increased cardiovascular mortality or HHF (hazard ratio 1.14; 95% confidence interval 1.02-1.26), but not all-cause mortality (hazard ratio 0.95; 95% confidence interval 0.81-1.11).. In this cohort of HHF patients with reduced EF, early post-discharge NT-proBNP trajectory was associated with a distinct clinical profile and carried independent prognostic value after adjustment for patient characteristics and absolute NT-proBNP level. Future prospective study of serial NT-proBNP measurement during the hospital and early post-discharge periods is warranted to validate these findings and evaluate post-discharge NT-proBNP trajectory as a therapeutic target.

Topics: Aged; Amides; Chronic Disease; Cohort Studies; Disease Progression; Female; Fumarates; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renin

This study was conducted to research the prognostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP), compare the utility of the Seattle Heart Failure Score (SHFS) with NT-proBNP, develop a risk-evaluation model based on NT-proBNP, assess the associations of NT-proBNP with patient characteristics, and screen for decisive factors of NT-proBNP in Chinese elderly with chronic heart failure (CHF).. There were 306 patients (≥60 years) with CHF chosen as study subjects. Each one received an assessment of NT-proBNP on serum. The end point was all-cause mortality during a mean follow-up period of 471 days.. Subjects had a median age of 85 (60-100) years, a median NT-proBNP of 1,743.4 pg/mL, and a median SHFS of 1.87. During the follow-up period, 104 deaths occurred. NT-proBNP was significantly related to mortality (odds ratio 1.603, 95% confidence interval 1.407-1.826; P<0.001) and the significance persisted after full adjustment (odds ratio 1.282, 95% confidence interval 1.103-1.489; P=0.001). Age, New York Heart Association class IV CHF, plasma albumin, and neutrophils/lymphocytes were also independent predictors for mortality (P<0.05 for all). NT-proBNP and the SHFS showed similar predictive capacities (0.736 versus 0.796, P=0.105). The addition of NT-proBNP to the SHFS (0.818 versus 0.796, P=0.168) generated marginal growth in the c-statistic. The model based on NT-proBNP consisting of all selected predictors in this study, including age, New York Heart Association class IV CHF, plasma albumin, neutrophils/lymphocytes, and NT-proBNP, had a moderately higher c-statistic compared with the SHFS (0.846 versus 0.796, P=0.066). NT-proBNP was bound with the SHFS (r=0.500, P<0.001). Characteristics regarding general condition, inflammation, and cardiac and renal function were the decisive factors of NT-proBNP (P<0.05 for all).. As a comprehensive representation of the patient characteristics described earlier, NT-proBNP values provided significant prognostic power similar to the SHFS in Chinese elderly with CHF. A novel model based on NT-proBNP could offer help for risk stratification.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; China; Chronic Disease; Comorbidity; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Severity of Illness Index

Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity.

Topics: Aged; Aged, 80 and over; Chronic Disease; Endothelium, Vascular; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Steam Bath; Stroke Volume; Vasodilation

International guidelines do not provide strong recommendations on the duration and intensity of follow-up after acute pulmonary embolism (PE), nor on screening-programs for chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to address this gab by performing an external validation of the easy "CTEPH rule-out-criteria" based on a normal NT-proBNP level and the absence of 3 ECG characteristics.. 134 patients underwent clinical follow-up 6months after PE. Predefined transthoracic echocardiographic (TTE) criteria were used to categorize patients as "PH unlikely" or "PH possible/likely". The latter patients underwent further (invasive) diagnostic procedures to confirm and classify the diagnosis of pulmonary hypertension. NT-proBNP and ECGs, both assessed at the day of echocardiography, were evaluated post-hoc.. Sixty-three patients (47%) scored none of the "CTEPH rule-out criteria" positive, of whom 61 had normal TTE (97%). Twenty-five patients (19%) were categorized by TTE as "PH possible/likely"; of those, 6 were diagnosed with CTEPH. The sensitivity of rule-out criteria for CTEPH was 100% (95%CI 56-100%; 6/6 patients identified), and for "PH possible/likely" on TTE 92% (95%CI 74-99%; 23/25 patients identified): 2 asymptomatic patients with estimated systolic pulmonary arterial pressure of 36mmHg and 38mmHg, respectively, who remained stable during further 2-year follow-up, were not identified. Inter-observer agreement for the adjudication of the ECG characteristics was excellent (kappa-statistic 0.97).. In this external validation cohort, we confirmed the diagnostic accuracy and reproducibility of the "CTEPH rule-out criteria". These results provide a solid ground for future outcome trials applying this algorithm.

Topics: Adult; Aged; Algorithms; Chronic Disease; Cohort Studies; Decision Support Systems, Clinical; Diagnosis, Computer-Assisted; Echocardiography; Female; Humans; Hypertension, Pulmonary; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Reproducibility of Results; Sensitivity and Specificity; Thromboembolism; Troponin T

Highly sensitive troponin (hsTn) assays may predict cardiovascular (CV) events and left ventricular (LV) remodeling in patients with heart failure (HF). In this study, 99 subjects with LV systolic dysfunction (LVSD) were followed 10 ± 3 months with serial measurement of hsTnI by a novel method. hsTnI was detectable in all subjects and was above the 99th percentile of a normal population in 56.7 %. Supramedian baseline hsTnI concentration was associated with higher-risk clinical features and shorter time-to-first event (p = 0.008). Across serial measurements, more time spent ≤ 10.9 pg/mL was associated with a lower CV event rate after adjustment (odds ratio (OR) = 0.81; p = 0.008); rising hsTnI also predicted progressive LV remodeling. In conclusion, hsTnI detected significant myocardial necrosis in a majority of patients with chronic HF due to LVSD and when measured serially, provided independent risk information for poor CV outcomes and deleterious LV remodeling.

Topics: Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Chronic Disease; Disease Progression; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardium; Natriuretic Peptide, Brain; Necrosis; Odds Ratio; Peptide Fragments; Phenotype; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Systole; Time Factors; Troponin I; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Data on the clinical outcomes and role of brain natriuretic peptide (BNP) levels in patients with chronic cor pulmonale are limited. A total of 69 patients with chronic cor pulmonale, admitted for dyspnea (January 2007 to September 2011) to three university hospitals, were retrospectively reviewed. All of the patients had right ventricular (RV) dysfunction on echocardiography. The median age was 70.0 yr, and chronic obstructive pulmonary disease (40.6%) and tuberculosis-destroyed lung (TDL, 27.5%) were the leading causes of chronic cor pulmonale. At the 1-yr follow-up, the mortality rate was 15.9%, and the readmission rate was 53.7%; patients with TDL had higher mortality (31.6% vs. 10.0%; P=0.059) and readmission rates (78.9% vs. 43.8%; P=0.009) than those with non-TDL diseases. The area under the receiver operating characteristic curve for admission BNP levels to predict readmission was 0.788 (95% confidence interval [CI], 0.673-0.904), and the sensitivity and specificity of the cut-off value were 80.6% and 77.4%, respectively. In multivariate analysis, high admission BNP levels were a significant risk factor for subsequent readmission (hazard ratio, 1.049; 95% CI, 1.005-1.094). Additionally, admission BNP levels were well correlated with cardiac troponin I (r=0.558), and delta BNP also correlated with delta RV systolic pressure (n=25; r=0.562). In conclusion, among hospitalized patients with chronic cor pulmonale, admission high BNP levels are a significant risk factor for subsequent readmission. Therefore, more intensive monitoring and treatment are needed in patients with higher BNP levels.

Topics: Aged; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Retrospective Studies; ROC Curve; Tuberculosis, Pulmonary

We explored the association between plasma growth differentiation factor 15 (GDF-15) levels and chronic heart failure (CHF) in coronary heart disease patients. We measured plasma GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in 269 untreated coronary heart disease patients (98 with CHF, 84 without CHF, and 87 control patients) using an enzyme-linked immunosorbent assay. All subjects were examined by echocardiography and left ventricular ejection fraction. We found that plasma GDF-15 levels in coronary atherosclerosis patients with CHF [median 1622.48 (25-75th percentile: 887.53-1994.93) ng/L] were higher than those in coronary atherosclerosis patients without CHF [944.99 (856.12-999.78) ng/L] and control patients (P < 0.05). NT-proBNP showed the same trend as GDF-15. We also used the New York Heart Association functional classification to subgroup CHF patients and found that the GDF-15 level was higher in all subgroup patients with CHF. After adjusting for covariates, plasma GDF-15 levels were found to be positively related to NT-proBNP (r = 0.861, P < 0.001) and negatively related to left ventricular ejection fraction (r = -0.936, P < 0.001). Furthermore, receiver operating characteristic curves of GDF-15 and NT-proBNP were constructed and the area under the curve for the untransformed GDF-15 and NT-proBNP was 0.804 and 0.795, respectively. Plasma GDF-15 levels and NT-proBNP are associated with CHF in coronary atherosclerosis patients and can be used as biomarkers.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Coronary Artery Disease; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ventricular Dysfunction, Left

Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86 ± 9.73, vs. 45.60 ± 5.51%; P=0.025) and left ventricular fractional shortening (25.31 ± 6.30, vs. 15.42 ± 8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07 ± 2.63, vs. 19.95 ± 5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11 ± 0.50, vs. 1.54 ± 0.57 cm(3); P=0.032) and left ventricular end systolic volume (0.50 ± 0.28, vs. 0.87 ± 0.36 cm(3); P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP.

Topics: Animals; Blood Pressure; Chronic Disease; Disease Models, Animal; Excitation Contraction Coupling; Heart Failure; Heart Rate; Heart Ventricles; Hemodynamics; Immunoenzyme Techniques; Male; Natriuretic Peptide, Brain; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Vagus Nerve Stimulation; Ventricular Function, Left; Ventricular Remodeling

In this study, we evaluated the prognostic value of plasma galectin-3 levels in patients with coronary heart disease (CHD) and chronic heart failure (HF) and selected 261 CHD patients who were consecutively admitted to our hospital. The enrolled chronic HF patients included HF patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Patients without HF served as the control group. Galectin-3 and B-type natriuretic peptide (BNP) levels were determined and the primary endpoint was the composite of all-cause mortality and rehospitalization with 12-month follow-up. Plasma galectin-3 levels were higher in HF patients compared with non-HF patients (P < 0.001). Receiver operating characteristic (ROC) analyses for diagnosis of HF showed that galectin-3 had the greatest area under the curve (AUC) of 0.756 (P < 0.001), with an optimal cutoff of 10.8 ng/mL, yielding a sensitivity of 81.7% and a specificity of 61.7%. Follow-up ROC analyses of galectin-3 for outcome prediction showed an optimal cutoff of 17.8 ng/ mL, yielding a sensitivity of 97.3% and a specificity of 77.6%. Galectin-3 yielded an AUC of 0.899 (P < 0.001), whereas the AUC of BNP was 0.633 (P = 0.022). Galectin-3 led to an AUC of 0.931 (P < 0.001) for HFpEF and an AUC of 0.882 (P < 0.001) for HFrEF. Cox proportional hazards regression analysis revealed that galectin-3 was an independent prognostic predictor for chronic HF, especially for HFpEF patients (RR: 1.231, 95% CI: 1.066-1.442). In summary, plasma galectin-3 levels were increased in CHD HF patients and were an independent predictor of all-cause mortality and rehospitalization. In HFpEF patients galectin-3 levels correlated stronger with outcomes than in HFrEF patients.

Topics: Aged; Area Under Curve; Biomarkers; Chronic Disease; Coronary Disease; Female; Follow-Up Studies; Forecasting; Galectin 3; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Proportional Hazards Models; ROC Curve; Stroke Volume

Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically.. Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441-2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14-0.20) cm) than in patients with HF (0.23 (0.17-0.33) cm; p<0.001) but similar during Valsalva (1.03 (0.90-1.16) cm vs 1.08 (0.90-1.25) cm; p=0.28). Consequently, JVD ratio was greater in controls (6.3 (4.9-7.6)) than in patients (4.5 (2.9-6.1); p<0.001). During a median follow-up of 516 (IQR 335-622) days, 48 patients (15%) with HF died or were hospitalised for HF. In multivariable models, among clinical, echocardiographic or biochemical variables, only increasing NT-proBNP and ultrasound assessment of internal jugular vein were independently associated with prognosis. Comparing top and bottom tertiles of JVD ratio (2.3 (IQR 1.7-2.9) versus 6.8 (6.1-7.7)), the tertile with lower values had a 10-fold greater risk of an adverse event (HR 10.05, 95% CI 3.07 to 32.93).. Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome.. NCT01872299.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Chi-Square Distribution; Chronic Disease; Elasticity; Female; Heart Failure; Hospitalization; Humans; Jugular Veins; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; Stroke Volume; Time Factors; Ultrasonography; Valsalva Maneuver; Ventricular Function, Left

To study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES).. Totally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared.. Compared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group.. Good curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.

Topics: Angiotensin II; Animals; C-Reactive Protein; Chronic Disease; Drugs, Chinese Herbal; Edema; Heart; Heart Failure; Heart Ventricles; Medicine, Chinese Traditional; Natriuretic Peptide, Brain; Qi; Rats; Rats, Sprague-Dawley; Syndrome; Thyrotropin; Ventricular Function, Left

To assess peak oxygen consumption (peak VO₂) derived from cardiopulmonary exercise testing (CPET), concentrations of NT-proBNP and echocardiographic changes in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF, <40%).. Seventy patients were included and divided into two groups according to the New York Heart Association (NYHA) classification: NYHA II group (17 cases) and NYHA III-IV group (53 cases). The basic clinical information, plasma concentration of NT-proBNP at rest, echocardiographic parameters and peak VO₂from CPET were compared between two groups. Correlation among peak VO₂, NT-proBNP and echocardiographic parameters in this patient cohort was assessed and their abilities to discriminate the NYHA III-IV grade were analyzed through c-Statistic.. Left atrial diameter ((51.3 ± 7.2) mm vs. (44.0±7.4) mm, P<0.001) was larger, plasma concentration of NT-proBNP (1 379-4 399 pmol/L vs. 1 109-2 356 pmol/L, P<0.01) was higher and peak VO₂((13.4 ± 3.5) ml·kg⁻¹·min⁻¹ vs. (18.2 ± 3.7) ml·kg⁻¹·min⁻¹, P<0.001) were significantly lower in NYHA III-IV group than those in NYHA II group. However, left ventricular end-diastolic diameter (LVEDD) and LVEF were similar between two groups. Peak VO₂correlated significantly with NT-proBNP (r=-0.311, P<0.01), but neither peak VO₂nor NT-proBNP correlated with echocardiographic parameters (LA, LVEDD and LVEF). ROC analysis showed that peak VO₂had the strongest discriminatory power for detecting NYHA III-IV grade patients (AUC=0.835, P<0.001), followed by the NT-proBNP (AUC=0.723, P<0.01).. Peak VO₂is a more sensitive parameter to detect the disease aggravation (NYHA III-IV grade) of the CHF patients with reduced LVEF compared to plasma NT-proBNP and echocardiographic parameters (LA, LVEDD, LVEF).

Topics: Chronic Disease; Echocardiography; Exercise Test; Heart; Heart Failure; Humans; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; ROC Curve; Ventricular Function, Left

Perceived quality of life (QoL) and psychological well-being represents an important target of secondary prevention practice in post-stroke patients. We aimed to identify the major covariates of impaired QoL in stable post-stroke patients and whether impaired QoL itself represents independent mortality predictor.The study consisted of a cross-sectional and a prospective part. Three hundred forty-one patients [mean age 69.0 (SD 9.1)] were interviewed at least 6 months after discharge from hospital for their first-ever ischemic stroke. QoL was objectivized using 36-Item Short-Form Health Survey (SF-36) scoring. Standard health-related questionnaires, including Hospital Anxiety and Depression Scale (HADS), risk factors, and biochemical markers, were assessed. To estimate the 5-year all-cause and cardiovascular mortality, we ascertained the vital status and declared cause of death.Anxiety, depression (HADS score ≥11), brain natriuretic peptide levels ≥100 ng/mL, residual motor impairment at interview, Rankin Scale ≥4 at discharge from hospitalization, and raised blood pressure were identified as main determinants of impaired QoL in the cross-sectional part. The 5-year all-cause and cardiovascular mortality rates were 25.8 and 19.9 %, respectively. After adjustment for potential covariates, patients with an SF-36 score ≤40 at baseline had more than a twofold higher risk of all-cause and cardiovascular mortality (with HRRs 2.01 (95 % CI 1.21-3.32), p < 0.007 and 2.32 (95 % CI 1.32-4.09), p < 0.003, respectively) during the 5 years of follow-up.In conclusion, anxiety, depression, and raised brain natriuretic peptide levels were the most important covariates of impaired QoL in post-stroke patients. Moreover, a decreased SF-36 score (≤40) represents an independent surrogate of increased additive mortality risk.

Topics: Aged; Anxiety; Chronic Disease; Cross-Sectional Studies; Depression; Female; Health Surveys; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Risk Factors; Stroke

Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH).. 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated.. MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %.. Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Chronic Disease; Endothelin-1; Exercise Tolerance; Female; Germany; Glycopeptides; Heart Atria; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Pulmonary Embolism; Pulmonary Wedge Pressure; Vascular Resistance

To investigate the effects of total flavonoids of propolis (TFP) on apoptosis of myocardial cells of chronic heart failure and its possible mechanism in rats.. Six male SD rats were randomly selected as normal control group, the remaining rats were made as chronic heart failure (CHF) model by intraperitoneal injection of adriamycin. The rats in the successful model were randomly divided into five groups (n = 6): CHF group, total flavonoids of propolis low dose group (LD group), total flavonoids of propolis middle dose group (MD group), total flavonoids of propolis high dose group (HD group), digoxin group (DIG group). After six week treatment, cardiac function indexes of rats were recorded by signal acquisition system; brain natriuretic peptide (BNP), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) content in plasma were detected; Myocardial morphological changes and collagen fiber hyperplasia by HE and Masson staining were observed; Myocardial apoptosis was detected with TUNEL method and protein connexin 43(P-Cx43) expression was detected by Western blot method.. Compared with NC group, left ventricular systolic pressure(LVSP) and maximal rise/fall velocity of left ventriculad pressure (± dP/dt(max)) absolute value in CHF group were significantly lowered (P < 0.01) while left ventricular end diastolic pressure (LVEDP) was increased significantly (P < 0.01); Contents of plasma BNP, cTnI, TNF-α and IL-6 in the CHF group were significantly improved (P < 0.01). Compared with CHF group, LVSP, ± dP/dt(max) absolute value in MD and HD groups were increased (P < 0.05), and LVEDP was significantly lowered (P < 0.01); LVEDP in LD group was significantly lowered (P < 0.01), changes in LVSP and ± dp/dt(max) absolue value were not obvious (P > 0.05). BNP, cTnI, TNF-α and IL-6 contents in MD and HD groups were significantly reduced (P < 0.01), but those plasma indicator changes were not obvious in LD group (P > 0.05). Western blot showed that P-Cx43 expression in CHF group was significantly higher than that in NC group (P < 0.01) and that in all TFP treatment groups it was decreased compared with CHF group (P < 0.05, P < 0.01), among which pairwise comparisons also showed differences (P < 0.05), myocardial apoptosis index (%)(22.62 ± 3.39) in CHF group was higher than that in NC group( 1.12 ± 0.24) (P < 0.01); compared with CHF group, the apoptosis index of myocardial cells (%) in LD,MD and HD groups, (15.79 + 2.8), (9.28 + 2.1) and (4.73 + 1.14) respectively, were significantly lower than those in the CHF group( P < 0.01). The expression level of P-Cx43 positively correlated with the apoptotic index (r = 0. 861, P < 0.01).. Total flavonaids of propolis have inhibitory effect on apoptosis of myocardial cells of chronic heart failure induced by adriamycin in rats, and the mechanism may be closely related to the regulation of Cx43 expression, especially the regulatory phosphorylation status.

Topics: Animals; Apoptosis; Chronic Disease; Connexin 43; Disease Models, Animal; Doxorubicin; Flavonoids; Heart Failure; Interleukin-6; Male; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phosphorylation; Propolis; Rats; Rats, Sprague-Dawley; Troponin I; Tumor Necrosis Factor-alpha

Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.. In chronic HF patients (n = 81, 76 ± 9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n = 17, 75 ± 11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r = 0.363, P < 0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

Topics: Aged; Aged, 80 and over; Albumins; Biomarkers; C-Reactive Protein; Ceruloplasmin; Chronic Disease; Cross-Sectional Studies; Female; Halogenation; Heart Failure; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Peroxidase

Osteonectin (OSN) plays a pivotal role in cardiac remodeling, but predictive value for OSN in ischemic chronic heart failure (CHF) has not been defined. The aim of the study was to evaluate the prognostic value of OSN for cumulative survival and hospitalization among patients with ischemic-induced CHF.. A total of 154 patients with ischemic symptomatic moderate-to-severe CHF were enrolled in the study at discharge from the hospital. Observation period was up to 3 years (156 weeks). Blood samples for biomarkers measurements were collected at baseline prior to study entry. ELISA methods for measurements of circulating level of OSN were used.. During a median follow-up of 2.18 years, 21 participants died and 106 subjects were re-admitted. Medians of circulating levels of OSN in survival and died patient cohorts were 670.96 ng/mL (95% confidence interval [CI] = 636.53-705.35 ng/mL) and 907.84 ng/mL (95% CI = 878.02-937.60 ng/mL). Receiver operation characteristic curve analysis has shown that cut off point of OSN concentration for cumulative survival function was 845.15 ng/mL. It has been found a significant divergence of Kaplan-Meier survival curves in patients with high (>845.15 ng/mL) and low (<845.15 ng/mL) concentrations of OSN. Circulating OSN independently predicted all-cause mortality (odds ratio [OR] = 1.23; 95% CI = 1.10-1.36; p < 0.001), CHF-related death (OR = 1.46; 95% CI = 1.22-1.80; p < 0.001), and also CHF-related re-admission (OR = 1.92; 95% CI = 1.77-2.45; p < 0.001) within 3 years of observation period.. Increased circulating secreted protein acidic and rich in cysteine family member OSN associates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Osteonectin; Peptide Fragments; Prospective Studies

Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR).. A group of patients with IDC underwent extensive non-invasive and invasive evaluation during a hospitalization period. The patients were further divided into two groups with AF (n = 19) and SR (n = 68).. Left atrial diameter was greater (P<0·001), left ventricular end-diastolic diameter smaller (P<0·05), left ventricular end-diastolic and end-systolic volumes smaller (P<0·01 for all), mean pulmonary artery pressure and pulmonary capillary wedge pressure higher (P<0·05 for both), cardiac output and maximal oxygen consumption lower (P<0·01 and P<0·05, respectively), and the levels of N-terminal pro-brain natriuretic peptide and interleukin-6 higher (P<0·05 for both) in AF group compared with SR group. Left ventricular ejection fraction and left ventricular end-diastolic pressure were similar in both groups.. In spite of otherwise more unfavourable prognostic factor profile, left ventricular size was observed to be smaller in chronic AF compared with SR in well-characterized patients with IDC. The confirmation and possible explainers of this paradoxical phenomenon need further studies in larger patient cohorts.

Topics: Adolescent; Adult; Aged; Arterial Pressure; Atrial Fibrillation; Biomarkers; Cardiomyopathy, Dilated; Chronic Disease; Female; Heart Atria; Heart Ventricles; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Pulmonary Wedge Pressure; Stroke Volume; Tomography, Emission-Computed, Single-Photon; Ultrasonography; Ventricular Function, Left; Young Adult

ST2 is a member of the interleukin-1 receptor family that is markedly upregulated in cultured cardiomyocytes subjected to mechanical strain. Serum soluble ST2 (sST2) levels can be detected in patients with acute myocardial infarction and severe chronic heart failure. This study sought to assess for the first time the activation of the ST2 pathway in patients with severe chronic degenerative mitral regurgitation.. Serum sST2 levels were measured in 20 patients scheduled for mitral valve (MV) repair at baseline, at the end of the intervention, on postoperative day 1, at hospital discharge, and after 6 months. Patients also underwent measurement of N-terminal pro-brain natriuretic peptide and echocardiographic evaluation at each time point.. At baseline, sST2 was detected in 10 (50%) patients (mean value, 60 ± 74 pg/mL; range, 0-234 pg/mL; median, 8 pg/mL). MV repair was performed successfully in all patients. Cardiac surgery with cardiopulmonary bypass was associated with a rapid and transient increase in sST2 levels. Patients with baseline higher versus lower sST2 levels (≥ 8 vs. < 8 pg/mL) had significantly higher levels of sST2 on postoperative day 1 (1,050 ± 593 vs. 440 ± 312 pg/mL; p = 0.009). At follow-up, patients with preoperative sST2 ≥ 8 pg/mL had significantly higher ejection fraction (EF) (64.7 ± 5.8 vs. 57.6 ± 5.9; p = 0.03) and lower left ventricular end-diastolic diameter (LVEDD) (50.6 ± 5.8 vs. 56 ± 4.2; p = 0.03) compared with patients with preoperative sST2 < 8 pg/mL.. Preoperative ST2 activation, evidenced by the presence of serum sST2 levels, is present in half of the patients with chronic degenerative mitral regurgitation and is associated with higher levels of EF and lower levels of LVEDD after MV repair.

Topics: Aged; Biomarkers; Cardiac Surgical Procedures; Chronic Disease; Echocardiography, Doppler, Color; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Cell Surface; Severity of Illness Index; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Experimental data imply that in decompensated heart failure (HF), the anti-angiogenic factor endostatin is increased. This study aimed to investigate whether the angiogenesis inhibitor endostatin is related to the risk of all-cause mortality in a prospective cohort study of chronic HF patients.. In this prospective observational cohort study, endostatin serum concentrations were determined in patients with chronic HF. Mortality data were recorded during a median follow-up of 31 months.. One fifty one patients were included. The overall mortality rate was 20%. Baseline endostatin concentrations > 245 ng/mL were associated with higher risk of all-cause mortality [HR 8·7 (95% CI 2·5-30·0); P = 0·001] in the multivariate analysis as compared to endostatin concentrations ≤ 245 ng/mL. When both endostatin and NT-proBNP were above the calculated cut-off of 245 ng/mL and 2386 pg/mL, respectively, the prognostic utility of both biomarkers increased [HR 40·8 (95% CI 4·7-354·6); P = 0·001] compared with values lower than the cut-offs.. Serum endostatin concentrations are independently associated with all-cause mortality. Furthermore, combination of endostatin and NT-proBNP discriminates patients at high risk.

Topics: Adult; Biomarkers; Chronic Disease; Endostatins; Epidemiologic Methods; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Young Adult

Although enhanced external counterpulsation (EECP) provides symptom reduction in many patients with severe angina pectoris, one-quarter of patients fail to respond. Earlier reports have not clearly established whether and how EECP responders may be identified pre-hoc. We hypothesized that clinical and biochemical data may be used to predict EECP response.. We explored a database of n=53 patients who had undergone clinically indicated EECP during 35 1-h sessions in our unit (65±7 years; 49 male), and sought to clarify which factors are predictive of response. Efficiency of counterpulsation was measured as the diastolic augmentation (DA) ratio, and was recorded both at beginning and end of the EECP treatment course. An increase in 6-min walk (6MW) distance of 5% was indicative of clinical response.. Response occurred in 28 patients (53%; nonresponse in n=25, 47%). Responders had shorter baseline 6MW distance (377±81 vs. 445±62 m; P<0.01), lower left ventricular ejection fraction (48±9 vs. 54±8%; P<0.05), frequently had an increase in DA ratio during the EECP treatment course (23/28 vs. 5/28 with unchanged or decreased DA ratio; P<0.05), and higher levels of N-terminal pro-brain natriuretic peptide [NT-proBNP; 256 (123-547) vs. 62 (26-444) ng/l, P<0.01]. In multivariate logistic regression, response was independently predicted by baseline 6MW distance and baseline NT-proBNP levels (P<0.05 for both; model sensitivity: 82%, specificity: 72%, accuracy: 79%).. There is larger clinical benefit of EECP in patients with greater functional impairment and higher levels of NT-proBNP.

Topics: Aged; Angina Pectoris; Biomarkers; Chi-Square Distribution; Chronic Disease; Counterpulsation; Diastole; Exercise Test; Exercise Tolerance; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Walking

The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting.. We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90).. Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance.

Topics: Acute-Phase Proteins; Adult; Aged; Biomarkers; Chronic Disease; Cohort Studies; Exercise Test; Female; Hospitalization; Humans; Hypertension, Pulmonary; Ireland; Lipocalin-2; Lipocalins; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Outpatients; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins; Risk Assessment; ROC Curve; Troponin T; Ventricular Dysfunction, Right

The clinical history of heart failure (HF) is usually characterized by frequent hospitalizations for decompensation. Therefore, several markers of subclinical hemodynamic congestion are under investigation for predicting early rehospitalization. In this field, the potential of ultrasound inferior vena cava (IVC) assessment has been recently investigated in HF but not yet assessed in the different aetiological categories.. Forty-eight patients admitted for decompensated HF (n = 25 with ischaemic heart disease [IHD] and n = 23 non-IHD) underwent biochemical examination (including NT-proBNP), echocardiography and IVC assessment by hand-carried ultrasound (HCU). During 60-day follow-up after discharge, the re-hospitalization rate for HF was recorded to investigate the predictive power of NT-proBNP and IVC assessment among the two study groups.. IHD and non-IHD patients with HF were similar except for gender distribution. During follow-up, 16·7% of patients were rehospitalized for decompensated HF, with higher prevalence in IHD group (28% vs. 4·3% P = 0·031). IVC assessment at discharge significantly predicted re-admission in the overall population and in IHD group, whereas NT-proBNP failed to predict rehospitalization in IHD group. In adjusted hazard ratio, only IVC min and the changes of IVC from admission significantly predicted re-admission. ROC analysis confirmed the change in IVC min as the best predictor of rehospitalization in patients with IHD.. This pilot study showed a higher early re-admission rate in patients with HF due to IHD. In addition, the change in IVC min diameter from admission to discharge was the best predictor of re-admission in patients with IHD.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Pilot Projects; Ultrasonography; Vena Cava, Inferior

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue receptor and is closely associated with chronic heart failure (CHF). We undertook this study to investigate the relevance of ghrelin in CHF prognosis.. A total of 145 in-patients with CHF in NYHA class II, III or IV despite optimized therapy were prospectively included in the study, grouped according to NYHA class and compared with 55 healthy control subjects. Ghrelin and N-terminal pro-B-type natriuretic peptide (Nt pro-BNP) were measured in plasma by ELISA. Echocardiographic information was also measured, including left atrial dimension, left ventricular end-diastolic diameter, LV volume and left ventricular ejection fraction (LVEF). Patients were followed for 2 years or until major adverse cardiac events.. Plasma ghrelin levels were significantly lower in patients with CHF than in control subjects (p = 0.014). In addition, plasma ghrelin levels differed significantly with the severity of CHF. Notably, survival analysis showed that high ghrelin levels were an indicator of a favorable prognosis for CHF. Our results also showed that ghrelin correlated inversely with plasma Nt pro-BNP levels (r = -0.562, p <0.001) and positively with LVEF (r = 0.620, p <0.001) in patients with CHF. Furthermore, multivariate analysis showed that ghrelin levels were independently associated with adverse cardiac events (hazard ratio: 0.72; 95% CI: 0.64-0.81, p = 0.03).. Ghrelin is a new biomarker of CHF severity as well as a new prognostic predictor for patients with CHF. Future experimental and clinical studies are warranted to evaluate ghrelin as a novel prognostic tool and for its therapeutic potential in patients with CHF.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chronic Disease; Female; Ghrelin; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Survival Analysis; Ultrasonography; Ventricular Function, Left

A paradoxical inspiratory rise in right atrial pressure (in contrast to the normal fall during inspiration), Kussmaul sign, has been described in congestive heart failure (CHF). However, the clinical and hemodynamic characteristics and clinical outcomes of patients with CHF and Kussmaul physiology have not been studied.. This is a single-center study of consecutive ambulant patients with CHF (New York Heart Association class III/IV) referred for assessment for heart transplantation between November 2011 and April 2013. Kussmaul physiology was defined as inspiratory rise in right atrial pressure during right heart catheterization. Clinical, biochemical, echocardiographic, and hemodynamic correlates were studied and outcomes assessed in patients with or without Kussmaul physiology after a mean follow-up of 379±227 days. Ninety ambulant patients (age, 53±12 years; 86% men) with CHF were studied. Kussmaul physiology was demonstrated in 39 (43%) patients, and it was associated with higher pulmonary pressures and lower cardiac index and pulmonary capacitance (all P<0.05). Patients with Kussmaul physiology were more likely to be treated with higher doses of diuretics, while higher filling pressures, N-terminal pro-B natriuretic peptide levels, and hyponatremia reflected greater neurohormonal activation. Echocardiography revealed greater left and right ventricular dimensions/volumes, restrictive transmitral filling pattern, and lower left ventricular ejection fraction and lower tricuspid annular plane systolic excursion. Peak oxygen uptake was low and comparable in both groups, but ventilation slope was higher in patients with Kussmaul physiology who also had a higher incidence of post-transplant right ventricular failure and overall mortality (P<0.05).. Kussmaul physiology is common in patients with CHF referred for heart transplantation and is associated with adverse cardiopulmonary hemodynamics. As a result of the latter, Kussmaul physiology is associated with poorer clinical outcomes. Kussmaul physiology may be useful during assessment of right heart function and pulmonary pressures before transplantation.

Topics: Adult; Aged; Cardiac Catheterization; Chronic Disease; Female; Heart Atria; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Inhalation; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Prospective Studies; Retrospective Studies; Risk Factors

Heart failure (HF) is a common, debilitating disorder in which the heart is unable to pump an adequate blood supply to the tissues. Although it has been shown that inflammation occurs in HF, inflammatory markers have yet to be defined. Inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), cytokines and serum sialic acid (SA) have been suggested as cardiovascular risk biomarkers. This study aims to assess the serum levels of inflammatory markers such as sialic acid and hs-CRP in chronic heart failure (CHF). Forty-eight patients with CHF and 30 healthy controls were recruited. Total sialic acid (TSA) and lipid-associated sialic acid (LASA), and the inflammatory marker hs-CRP, were assayed in all study subjects. N-terminal pro-brain natriuretic peptide (NT-proBNP) was assayed in the patient group only. Serum mean TSA and LASA were significantly higher in CHF patients when compared to healthy controls (P < 0.01). Mean hs-CRP levels in CHF patients showed a significant elevation compared with healthy controls (P < 0.01). There was a significant positive correlation between TSA and hs-CRP. Thus, TSA and hs-CRP would appear to be stable markers of systemic inflammation in chronic heart failure.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; N-Acetylneuraminic Acid; Natriuretic Peptide, Brain; Peptide Fragments

Pulmonary endarterectomy (PEA) is established for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary arteries. A shift in clinical practice of interventional therapies occurred in 2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of patients with CTEPH.. This study retrospectively included 136 patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and the other 107 underwent interventional therapies (Interventions-group) (39 underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis, 5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline hemodynamic parameters were significantly more severe in the Interventions-group, the outcome after the diagnosis was much better in the Interventions-group than in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic improvement in the PEA-group was a 46% decrease in mean pulmonary arterial pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up period; 74.7 ± 32.3 months), while those in the PTPA-group were a 40% decrease in mean PAP and a 49% decrease in TPR (follow-up period; 17.4 ± 9.3 months). The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival rate, occurrence of right heart failure, and re-vascularization rate in the PEA-group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%, and 2.9%, respectively.. The patients who underwent interventional therapies had better results than those treated only with drugs. The availability of both of these operative and catheter-based interventional therapies leads us to expect the dawn of a new era of therapeutic strategies for CTEPH.

Topics: Angioplasty; Chronic Disease; Endarterectomy; Endpoint Determination; Exercise; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Treatment Outcome

To assess the prognostic implications of the 6-minute walk test (6-MWT) distance measured twice, one year apart, in a large sample of patients with chronic heart failure (CHF) followed for an extended period (>8 years from baseline).. Patients undertook a 6-MWT at baseline and at one year, and were followed up for 8 years from baseline.. Six hundred patients (median [inter-quartile range, IQR]) (age 78 [72-84] years; 75% males; body mass index 27 [25-31] kg·m(-2); left ventricular ejection fraction 34 [26-38] %) were included. At baseline, median 6-MWT distance was 232 (60-386) m. There was no significant change in 6-MWT distance at one year (change -12m; P=0.533). During a median follow-up of 8.0 years in survivors, 396 patients had died (66%). Four variables were independent predictors of all-cause mortality in a multivariable Cox model (adjusted for body mass index, age, QRS duration, left ventricular ejection fraction); increasing NT pro-BNP, decreasing 6-MWT distance at 1 year, decreasing haemoglobin, and increasing urea.. Distance walked during the 6-MWT is an independent predictor of all-cause mortality in patients with CHF. In survivors, the 6-MWT distance is stable at 1 year. The 6-MWT distance at 1 year carries similar prognostic information.

Topics: Aged; Aged, 80 and over; Chronic Disease; Exercise Test; Female; Follow-Up Studies; Heart Failure; Hemoglobins; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Survival Rate; Urea; Walking

The prognosis in patients with chronic heart failure (CHF) is poor. ST2 protein is a promising prognostic biomarker for CHF. ST2 belongs to the cardioprotective signalling pathway involving interleukin-33 and its concentration in the serum depends on the biomechanical stress of cardiomyocytes (biomechanical strain).. To determine the prognostic value of ST2 in short term follow-up after hospitalisation among patients with CHF.. The study included 167 patients (mean age 62 years, 83% men) in stable NYHA class I-III with left ventricular ejection fraction (LVEF) of ≤ 45% (average 29.65%, ranges 13-45%). We analysed 58 variables including: demographics, co-morbidities, resting ECG, echocardiographic and coronary arteriography data, basic laboratory tests including N-terminal prohormone B-type natriuretic peptide (NT-proBNP), serum concentration of soluble form of ST2 (sST2) using quantitative ELISA test ST2 Kit (Medical and Biological Laboratories; Japan) and adverse cardiovascular events during a one year observation. In the study, the primary endpoint (death) and the composite endpoint (hospitalisation for HF worsening, worsening in NYHA functional class, the need to increase the dose of diuretics, and/or death in a one year observation) were determined.. Patients who died (n = 24; 14.55%) were in more advanced NYHA class, had prolonged QRS duration, higher levels of sST2, NT-proBNP, and lower estimated glomerular filtration rate. From multivariate analysis, the independent variable for the primary endpoint was NT-proBNP (OR = 1.00012; 95% CI 1.00002-1.00022; p = 0.018). 93 (56%) patients reached the composite endpoint. Multivariate analysis revealed that fasting glucose (OR = 1.343; 95% CI 1.041-1.732; p = 0.023) and sST2 (OR = 3.593; 95% CI 1.427-9.05; p = 0.007) independently enhanced the risk of composite endpoint occurrence in a one year observation.. In patients with CHF with LVEF ≤ 45%, the prognostic value of sST2 protein in a short-term observation of one year was confirmed. sST2 protein was an independent variable for the composite endpoint, which consisted of worsening NYHA functional class, hospitalisation for worsening of HF, the need to increase the dose of diuretics, and/or death.

Topics: Aged; Biomarkers; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Function, Left

Vascular diseases are the most prevalent diseases worldwide. This study intended to analyze peripheral blood miRNA levels and their correlation with NT-pro-BNP and cTN-I in patients with atherosclerosis or pre-atherosclerotic conditions to build a dynamic correlation between vascular diseases and their biomarkers. Serum NT-pro-BNP and cTN-I levels were measured by their respective ELISA kits. The miRNA levels were assayed by quantitative PCR. Unique miRNA signatures were identified for both atherosclerosis and pre-atherosclerosis. The levels of miR-92a, 126, 130a, 222, and 370 levels were decreased in the peripheral blood of pre-atherosclerotic subjects. In atherosclerosis, miR-21, 122, 130a, and 211 were significantly increased whereas miR-92a, 126, and 222 were markedly decreased. Serum levels of NT-pro-BNP and cTN-I correlated with each other and increased with the progression of atherosclerosis. Moreover, the levels of cTN-I and NT-pro-BNP were positively correlated with miR-21 and negatively correlated with miR-126. Integrating specific pattern of miRNA levels with NT-pro-BNP and/or cardiac troponin may improve the diagnosis of cardiovascular diseases.

Topics: Atherosclerosis; Biomarkers; Case-Control Studies; Chronic Disease; Diabetes Mellitus; Disease Progression; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Real-Time Polymerase Chain Reaction; ROC Curve; Troponin T

To verify whether a combined assessment of left-ventricular filling pattern at Doppler echocardiography, plasma levels of brain natriuretic peptide (BNP) and high-sensitive troponin I (hsTnI) improves prognostic stratification in patients with chronic systolic heart failure.. Three predictors of prognosis were evaluated in 200 consecutive outpatients with heart failure and left-ventricular ejection fraction 35% or less: left-ventricular filling pattern at Doppler echocardiography, BNP plasma levels and hsTnI plasma levels.. During a median follow-up period of 44 months, 15 deaths, two urgent cardiac transplantations, two episodes of ventricular fibrillation and 50 heart failure hospitalizations were observed. The end point of survival analysis was the composite of hard events and hospitalization for acute heart failure. At univariable analysis, the E-wave deceleration time at Doppler echocardiography and BNP plasma level on a continuous log-scale were significantly associated with event-free survival, whereas hsTnI plasma level was not statistically significant. A hierarchical multivariable analysis was performed including a restrictive left-ventricular filling pattern at Doppler as the first prognostic indicator; the subsequent addition of BNP plasma levels above 138  pg/ml (median value) and hsTnI above 0.018  ng/ml (median value) did not further improve prognostic stratification.. A restrictive left-ventricular filling pattern at Doppler echocardiography is the most important prognostic indicator in chronic heart failure patients. Plasma levels of BNP and hsTnI do not provide additional relevant information to identify patients at higher risk of cardiovascular outcomes.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Troponin I; Ventricular Function, Left

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Topics: Aldosterone; Animals; Cardiotonic Agents; Chronic Disease; Collagen; Cytochrome P-450 CYP11B2; Disease Models, Animal; Echocardiography; Fibrosis; Heart Failure; Hemodynamics; Humans; Isoproterenol; Long-Term Care; Male; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Transcription, Genetic; Ventricular Remodeling

sST2 protein is a new biomarker. Its prognostic value in chronic heart failure (CHF) is still unclear.. The aim of the study was to evaluate the value of sST2 protein in patients with CHF during 1-year follow-up after hospitalization for prediction of adverse events: cardiovascular death, rehospitalization, an increase in diuretic doses, and/or worsening of the New York Heart Association functional class, defined as the composite endpoint.. The study involved 145 consecutive patients (mean age, 62.16 ±11.25 y; men, 82.76%) with left ventricular (LV) ejection fraction of 30% or less and symptomatic CHF. We analyzed clinical and biochemical data along with the serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and sST2. The optimal cut-off points for significant predictors of the composite endpoint were determined using receiver operating characteristi c curves.. Patients with elevated levels of sST2 and NT-proBNP had more than a 4-fold higher risk of composite endpoint (odds ratio [OR], 4.033; 95%CI, 1.540-10.559) compared with patients in whom both biomarkers were below the cut-off points. The C-statistic for predicting the composite endpoint was improved when both biomarkers were incorporated into the model (C-statistic, 0.692; P = 0.0001) compared with an individual analysis for NT-proBNP (C-statistic, 0.606; P = 0.009) and sST2 (C-statistic, 0.613; P = 0.003). Moreover, after the addition of sST2 to NT-proBNP, the continuous net reclassification improvement index (OR, 0.256; 95% CI, 0.090-0.401; P = 0.007) and the integrated discrimination improvement index (OR, 0.104; 95% CI 0.011-0.221; P = 0.007) significantly improved.. A single measurement of sST2 levels on admission in patients with poor LV systolic function and stable CHF is useful in short-term risk stratification and, in combination with NT-proBNP, it could be more useful in identifying patients with unfavorable c ourse of CHF.

Topics: Aged; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peptides, Cyclic; Predictive Value of Tests; Prognosis; Prospective Studies; Receptors, Somatostatin

Topics: Adult; Biomarkers; Blood Pressure; Chronic Disease; Female; Humans; Hypertension, Pregnancy-Induced; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Pregnancy; Protein Precursors

The optimum timing of surgery in asymptomatic patients with chronic severe primary degenerative mitral regurgitation (MR) remains controversial, and further markers are needed to improve decision-making. There are limited data that wall stress is increased in MR and may result in ventricular fibrosis. We investigated the hypothesis that chronic volume overload in MR is a stimulus for myocardial fibrosis using T1-mapping cardiac MRI.. A cross-sectional study of 35 patients (age 60 ± 14 years) with asymptomatic moderate and severe primary degenerative MR (mean effective regurgitant orifice area, 0.45 ± 0.25 cm)(2) with no class I indication for surgery were compared with age and sex controls. Subjects were studied with cardiopulmonary exercise testing, echocardiography, and cardiac MRI. Longitudinal and circumferential myocardial deformation was reduced with MR when left ventricular ejection fraction (67% ± 10%) and N-terminal pro B Natriuretic peptide (126 [76-428] ng/L) were within the normal range. Myocardial extracellular volume was increased (0.32 ± 0.07 versus 0.25 ± 0.02, P<0.01) and was associated with increased left ventricular end-systolic volume index (r=0.62, P<0.01), left atrial volume index (r=0.41, P<0.05) but lower left ventricular ejection fraction (r=-0.60, P<0.01), longitudinal function (mitral annular plane systolic excursion, r=-0.46, P<0.01), and peak VO2 max (r=-0.51, P<0.05). In a multivariable regression model, left ventricular end-systolic volume index and left atrial volume index were independent predictors of extracellular volume (r(2)=0.42, P<0.01).. Patients with asymptomatic MR demonstrate a spectrum of myocardial fibrosis associated with reduced myocardial deformation and reduced exercise capacity. Future work is warranted to investigate whether left ventricle fibrosis affects clinical outcomes.

Topics: Aged; Asymptomatic Diseases; Biomarkers; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Echocardiography, Doppler; Echocardiography, Transesophageal; Exercise Test; Exercise Tolerance; Female; Fibrosis; Heart Ventricles; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

To explore the predict value of plasma soluble ST2 (sST2) on one-year mortality for hospitalized patients with chronic heart failure (HF).. A total of 1 244 consecutive hospitalized patients admitted to Heart Failure Center Fuwai Hospital between March 2009 and July 2012 and with HF as their primary diagnosis were included. Plasma sST2 was measured in all patients and patients were followed up for 1 year, and the primary endpoint was defined as all-cause death.. There were 193 deaths during follow up. sST2 concentrations at admission were positively correlated with NT-proBNP, NYHA functional class and heart rate, and negatively correlated with left ventricular ejection fraction, blood sodium, total cholesterol and glomerular filtration rate at admission. sST2 concentrations were significantly higher in non-survivors compared with survivors (P < 0.001). Multivariable Cox regression analyses showed that sST2 independently predicted 1-year mortality (per 1 log unit, hazard ratio 1.87, 95% confidence interval: 1.56 to 2.25, P < 0.001). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.776 which was similar to that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (AUC = 0.775). The prognostic value was improved when combining these two biomarkers together (AUC = 0.813).. sST2 concentration at admission is correlated with clinical and biochemical indexes and associated with 1-year mortality for hospitalized patients with HF.

Topics: Biomarkers; Cause of Death; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; ROC Curve; Ventricular Function, Left

To elucidate predictors of unfavorable cardiac events in patients with non-ischemic cardiomyopathy (CMP) complicated by congestive heart failure (CHF) with preserved myocardial coronary reserve (MCR).. We followed 114 patients with non-ischemic MCP and NYHA class III-IV CHF. MCR was estimated by dobutamine stress-echocardiography (SEchoCG). Prior to SEchoCG we measured blood von Willebrand factor (vWF) activity, content of endothelin-1 (ET), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1) and nitric oxide stable metabolites. At peak of dobutamine test blood was collected for measurement of ET, vWF, and NT-proBNP concentrations. Left ventricular ejection fraction (LVEF)sechoCG, ETsechoCG, vWFsechoCG and NT-proBNPsechoCG were calculated as percentage changes of these parameters from baseline at peak dobutamine load.. Groups with low and preserved MCR were not different by relative number of patients with unfavorable course of the disease (41.2 and 34.8%, p = 0.529, respectively). The following parameters were predictors of development of unfavorable cardiac events in patients with preserved MCR (LVEFsechoCG > 10%) during 24 months: initial hsCRP > 5.2 mg/ml, LVEFsechoCG < 19.7% and ETsechoCG > 11.8%. Logistic regression model combined with binary values of LVEFsechoCG and ETsechoCG demonstrated best prognostic efficacy (sensitivity--86.7%, specificity--83.3%, prognostic accuracy--84.6%).

Topics: Adult; C-Reactive Protein; Chronic Disease; Disease Progression; Echocardiography, Stress; Endothelin-1; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Vascular Cell Adhesion Molecule-1; Ventricular Function, Left; von Willebrand Factor

Chronic heart failure (CHF) is one of the most important public health concerns in the industrialized world having increasing incidence and prevalence. Although there are several studies describing the prevalence of heart failure with reduced ejection fraction (HFREF) and heart failure with normal ejection fraction (HFNEF) in selected populations, there are few data regarding the prevalence and the determinants of symptomatic heart failure in the general population.. Cross-sectional data of a population-based German sample (1,779 subjects aged 45-83 years) were analyzed to determine the prevalence and determinants of chronic SHF and HFNEF defined according to the European Society of Cardiology using symptoms, echocardiography and serum NT-proBNP. Prevalence was age-standardized to the German population as of December 31st, 2005.. The overall age-standardized prevalence of symptomatic CHF was 7.7% (95%CI 6.0-9.8) for men and 9.0% (95%CI 7.0-11.5) for women. The prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be shown in 48% (n = 78), symptomatic HFNEF in 52% (n = 85) of subjects with CHF. The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8) for women and 4.6 % (95%CI 3.6-6.3) for men. The age-standardized prevalence of HFNEF for women and men was 5.1 % (95%CI 3.8-7.0) and 3.0 % (95%CI 2.1-4.5), respectively. Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3) or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5).. The prevalence of symptomatic CHF appears high in this population compared with other studies. While more women were affected by HFNEF than men, more male subjects suffered from HFREF. The high prevalence of symptomatic CHF seems likely to be mainly due to the high prevalence of cardiovascular risk factors in this population.

Topics: Age Factors; Aged; Aged, 80 and over; Chronic Disease; Female; Germany; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Risk Factors; Stroke Volume; Ultrasonography

Knowledge of the role of the receptor for advanced glycation end products (RAGE), particularly its soluble form (sRAGE), and of its advanced glycation end product (AGE) ligand, N-(carboxymethyl)lysine adducts (CML), is limited in chronic heart failure (CHF) and in chronic obstructive pulmonary disease (COPD). We evaluated whether the AGE/RAGE system is activated in stable CHF and COPD, and whether plasma sRAGE and CML levels are affected by clinical and functional parameters.. We measured plasma levels of sRAGE and CML using a sandwich enzyme-linked immunosorbent assay (ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study.. Plasma levels of sRAGE and CML were higher in CHF patients than in controls [sRAGE: 0.48 (0.37-0.83) vs. 0.42 (0.29-0.52) ng/mL, P = 0.01; CML: 1.95 (1.58-2.38) vs. 1.68 (1.43-2.00) ng/mL, P = 0.01]. By contrast, sRAGE and CML were not different between both COPD and CHF+COPD patients and controls (P > 0.05). N-terminal pro-brain natriuretic peptide (Nt-pro BNP) correlated with sRAGE, but not with CML, in the patient groups: CHF (r = 0.43, P < 0.001), COPD (r = 0.77, P < 0.0001) and CHF/COPD (r = 0.43, P = 0.003).. Plasma levels of sRAGE and CML are increased in CHF, but not in COPD patients. The robust association between NT-pro BNP, a diagnostic and prognostic marker in CHF, and sRAGE concentrations might suggest a possible BNP pathway of amplification of inflammation via the AGE/RAGE system.

Topics: Aged; Biomarkers; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Glycation End Products, Advanced; Heart Failure; Humans; Lysine; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive

There is no agreement in current publications regarding the reliability of serum concentrations of natriuretic peptides (NPs) to detect dogs with subclinical myxomatous mitral valve disease (MMVD) and to differentiate between asymptomatic stages.. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-proBNP) and pro-atrial natriuretic peptide 31-67 (proANP) concentrations between various stages of canine MMVD and to investigate the influence of age, weight, and sex.. In this prospective study, dogs were classified in different disease stages using the modified Canine Heart failure International Expert Forum (CHIEF) system. Serum NP concentrations were compared between groups.. A total of 559 samples from 116 healthy dogs and 236 dogs with MMVD were analyzed. Using cut-off values (1207 pmol/L for NT-proBNP, 1578 fmol/mL for proANP), dogs with MMVD with and without congestive heart failure (CHF) could be differentiated with a sensitivity of 83% for both and specificities of 85% and 86%, respectively. Dogs staged in CHIEF B1 and B2 could not be distinguished based on NP concentrations due to wide variation within the groups. Intact females (means 598 pmol/L and 1036 fmol/mL, respectively) had significantly higher values of both NPs than intact males (315 pmol/L and 836 fmol/mL).. NPs in canine MMVD are useful to discriminate between asymptomatic dogs and dogs with CHF. Due to a large overlap of NP-concentrations between the groups, NPs do not seem to be useful to differentiate between dogs in stages B1 and B2. Interpretation of NT-proBNP and proANP values should include consideration of sex-specific differences.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Chronic Disease; Dog Diseases; Dogs; Female; Heart Failure; Heart Valve Diseases; Male; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Sex Factors

An accurate prognosis prediction represents a key element in chronic heart failure (CHF) management. Seattle Heart Failure Model (SHFM) prognostic power, a validated risk score for predicting mortality in CHF, is improved by adding B-type natriuretic peptide (BNP). We evaluated in a prospective study the incremental value of several biomarkers, linked to different biological domains, on death risk prediction of BNP-added SHFM.. Troponin I (cTnI), norepinephrine, plasma renin activity, aldosterone, high sensitivity-C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 2 soluble receptor, leptin, prealbumin, free malondialdehyde, and 15-F2t-isoprostane were measured in plasma from 142 consecutive ambulatory, non-diabetic stable CHF (mean NYHA-class 2.6) patients (mean age 75±8years). Calibration, discrimination, and risk reclassification of BNP-added SHFM were evaluated after individual biomarker addition.. Individual addition of biomarkers to BNP-added SHFM did not improve death prediction, except for prealbumin (HR 0.49 CI: (0.31-0.76) p=0.002) and cTnI (HR 2.03 CI: (1.20-3.45) p=0.009). In fact, with respect to BNP-added SHFM (Harrell's C-statistic 0.702), prealbumin emerged as a stronger predictor of death showing the highest improvement in model discrimination (+0.021, p=0.033) and only a trend was observed for cTn I (+0.023, p=0.063). These biomarkers showed also the best reclassification statistic (Integrated Discrimination Improvement-IDI) at 1-year (IDI: cTnI, p=0.002; prealbumin, p=0.020), 2-years (IDI: cTnI, p=0.018; prealbumin: p=0.006) and 3-years of follow-up (IDI: cTnI p=0.024; prealbumin: p=0.012).. Individual addition of prealbumin allows a more accurate prediction of mortality of BNP enriched SHFM in ambulatory elderly CHF suggesting its potential use in identifying those at high-risk that need nutritional surveillance.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cohort Studies; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Pilot Projects; Prealbumin; Predictive Value of Tests; Prospective Studies; Risk Factors; Washington

Hypothalamic axis deregulation is associated with clinical severity and depression in chronic heart failure (CHF). We investigated the relationship of serum prolactin, an indicator of hypothalamic axis function, to neurohomonal/immune activation and depressive symptoms in CHF as well as its prognostic value.. Serum prolactin was determined in 180 patients with advanced CHF (aged 65 ± 12 years, mean LVEF 27 ± 7%) along with natriuretic peptides (BNP), inflammatory cytokines, endothelial adhesion molecules, 6 min walk test (6MWT), and the Zung self-rating depression scale (SDS). Patients were followed for all-cause death or hospitalization for cardiovascular reasons for up to 8 months. Prolactin levels were significantly correlated with NYHA class (r = 0.394, P < 0.001), LVEF (r = -0.314, P < 0.001), 6MWT (r = -0.353, P < 0.001), BNP (r = 0.374, P < 0.001), Zung SDS (r = 0.544, P < 0.001), interleukin-6 (IL-6) (r = 0.451, P < 0.001), IL-10 (r = -0.426, P < 0.001), tumour necrosis factor (TNF)-α (r = 0.310, P = 0.001), soluble Fas (r = 0.333, P < 0.001), soluble Fas-ligand (r = 0.517, P < 0.001), soluble intercellular adhesion molecule-1 (ICAM-1) (r = 0.409, P < 0.001), and soluble vascular cell adhesion molecule-1 (VCAM-1) (r = 0.480, P < 0.001). During follow-up, 119 patients (66%) died or were hospitalized for cardiovascular events after a median time of 72 days (range 5-220 days); these patients had higher baseline prolactin levels (10.2 ± 5.7 vs. 6.7 ± 4.3 ng/mL, P < 0.001), and a prolactin value ≥4.5 ng/mL was associated with a higher rate of death or hospitalization (116 ± 7 vs. 181 ± 11 days, P = 0.0001). In multivariate analysis, prolactin levels remained an independent predictor of death or hospitalization (<4.5 vs. ≥4.5 ng/mL; odds ratio, 0.368; 95% confidence interval 0.148-0.913; P = 0.031), along with BNP (P < 0.001) and 6MWT (P = 0.020).. Serum prolactin is associated with neurohormonal/immune activation and depressive symptoms and is an independent predictor of prognosis in advanced CHF.

Topics: Aged; Chronic Disease; Cytokines; Depression; Exercise Test; Fas Ligand Protein; Female; Heart Failure; Humans; Hypothalamo-Hypophyseal System; Interleukin-10; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Pituitary-Adrenal System; Prognosis; Prolactin; Proportional Hazards Models; Severity of Illness Index; Stroke Volume; Tumor Necrosis Factor-alpha

Recent studies have suggested that carbohydrate antigen 125 (CA 125) serum levels are remarkably elevated in patients with heart failure. We hypothesized that there was a relationship between serum levels of tumor markers and the four stages of chronic heart failure (CHF) in patients aged 85 years and older with CHF.. The retrospective study enrolled 2115 patients aged 85 years and older suffering from CHF between January 2004 and January 2011. The levels of various tumor markers, N-terminal proB-type natriuretic peptide (NT-proBNP) in the different stages of CHF, and clinical risk factors were analyzed. All patients were followed for 180 days, and major cardiovascular events were recorded.. Only the CA 125 level increased as the stage of CHF increased (p<0.05) among the tumor markers. Significantly higher CA 125 serum levels were found in patients with pleural fluids or peripheral edema, compared with patients without pericardial effusion or peripheral edema (p<0.01). During 180 days of follow-up, CA 125 values were significantly higher in patients who died or were rehospitalized, compared with those who remained alive or did not undergo rehospitalization. Linear regression analysis between CA 125 and NT-proBNP serum levels showed a statistically significant relation (r=0.5103, p<0.05).. Among the tumor markers evaluated, only CA 125 appeared to be related to the severity of CHF and NT-proBNP, along with the presence of pleural fluid or peripheral edema in patients aged 85 years and older with CHF.

Topics: Age Factors; Aged, 80 and over; Biomarkers, Tumor; CA-125 Antigen; Chronic Disease; Edema; Female; Heart Failure; Humans; Linear Models; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Effusion; Retrospective Studies; Severity of Illness Index

To study the predictive value of plasma galectin-3 in patients with chronic heart failure (CHF).. Patients with CHF (New York Heart Association functional class II-IV) caused by coronary heart disease were recruited. The levels of plasma galectin-3 and NT-proBNP were measured by enzyme-linked immuno sorbent assay. Echocardiography was performed to determine the diastolic left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF). Receiver-operating characteristic (ROC) curve was used to analyze the prognostic value of galectin-3 or NT-proBNP for CHF.. The level of galectin-3 was significantly higher in NYHA functional class III and IV compared with that in control (p < 0.05 and p < 0.01, respectively). The level of plasma galectin-3 was positively correlated with LAD (r = 0.271, p < 0.05) and LVEDD (r = 0.480, p < 0.01), but negatively correlated with LVEF (r = -0.683, p < 0.01). The level of plasma NT-proBNP was positively correlated with LAD (r = 0.481, p < 0.01) and LVEDD (r = 0.270, p < 0.05), but negatively correlated with LVEF (r = -0.516, p < 0.01). AUC was 0.798 when the level of plasma galectin-3 was more than 7.52 ng/ml. The sensitivity to predict CHF was 62.9%, and the specificity was 90%. AUC was 0.901 when the level of plasma NT-proBNP was more than 1143 pg/ml. The sensitivity to predict CHF was 92.8% and the specificity was 85%.. The level of plasma galectin-3 is related to the changes of left ventricular structure and function, indicating that galectin-3 may have been involved in the process of left ventricular remodeling in CHF. The specificity of galectin-3 to predict CHF is higher than NT-proBNP, but not the sensitivity.

Topics: Aged; Chronic Disease; Female; Galectin 3; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; ROC Curve; Ventricular Function, Left

Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF.. A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 ± 3 months. The amount of time spent with a galectin-3 level ≤ 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P = 0.03; 21.7 vs. 16.5 ng/mL, P = 0.03; 23.2 vs. 16.0 ng/mL, P = 0.007). Galectin-3 concentration changed in 35.2% of subjects during study procedures; time spent at ≤ 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) = 0.90; P = 0.05], and predicted increase in LV ejection fraction (OR = 1.20; P = 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P = 0.02). There were no significant effects of medications on galectin-3 levels.. In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Proteins; Chronic Disease; Disease Progression; Diuretics; Echocardiography; Female; Galectin 3; Galectins; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prognosis; Treatment Outcome; Ventricular Remodeling

Chronic Chagas disease afflicts millions of patients in Latin America of which 70% remain asymptomatic but 30% develop fatal heart injury. To evaluate the impact of laboratory medicine for diagnosis and guiding of patients with Chagas' heart disease, we measured N-terminal B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT).. NT-proBNP and cTnT using the highly sensitive assay (hs-cTnT) were measured in 48 asymptomatic Chagas' patients (control group; (-) CM), and in symptomatic patients who suffered from mild/moderate (group (+/++) CM, n=62) or severe cardiomyopathy (group (+++) CM, n=27).. Both markers were higher in (+/++) CM and (+++) CM vs. (-) CM and increased in the cardiomyopathy severity. Values of 3 ng/L cTnT and 160 ng/L NT-proBNP were calculated as optimal cut-offs to distinguish (-) CM vs. CM. The NT-proBNP cut-off of 125ng/L, as recommended by international guidelines, was additionally incorporated in the analysis. Cardiomyopathy was most successfully predicted by dual positivity of both markers (positive predictive value=1.0). Negativity of both markers effectively excluded cardiomyopathy (negative predictive value of 0.85). Positivity for at least one of the markers is the best for overall correct classification.. Combined measurement of hs-cTnT and NT-proBNP can be used for diagnosis and monitoring of cardiomyopathy in chronic Chagas' patients. In this way, laboratory medicine increases the pre-test probability of the cardiologic diagnostics, which would reduce its time, cost, and logistical problems.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Chagas Cardiomyopathy; Chronic Disease; Disease Progression; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Troponin T

Development of atrial fibrillation (AF) is complexly associated with electrical and structural remodeling and other factors every stage of AF development. We hypothesized that P wave electrocardiography with an elevated brain natriuretic peptide (BNP) level would be associated with the progression to persistence from paroxysmal AF.. P wave electrocardiography such as a maximum P wave duration (MPWD) and dispersion by 12-leads ECG, heart/mediastinum (H/M) ratio by delayed iodine-123 metaiodobenzylguanidine scintigraphic imaging, left ventricular ejection fraction (LVEF), and left atrial dimension (LAD) by echocardiography, and plasma BNP level were measured to evaluate the electrical and structural properties and sympathetic activity in 71 patients (mean ± standard deviation, age: 67 ± 13 years, 63.4 % males) with idiopathic paroxysmal AF.. Over a 12.9-year follow-up period, AF developed into persistent AF in 30 patients. A wider MPWD (>129 ms) (p = 0.001), wider P wave dispersion (>60 ms) (p = 0.001), LAD enlargement (>40 mm) (p = 0.001), higher BNP level (>72 pg/mL) (p = 0.002), lower H/M ratio (≤2.7) (p = 0.025), and lower LVEF (≤60 %) (p = 0.035) were associated with the progression to persistent AF, and the wide MPWD was an independently powerful predictor of the progression to persistent AF with a hazard ratio (HR) of 5.49 [95 % confidence interval (CI) 2.38-12.7, p < 0.0001] after adjusting for potential confounding variables, such as age and sex. The combination of wide MPWD and elevated BNP level was additive and incremental prognostic power with 13.3 [2.16-13, p < 0.0001].. The wide MPWD with elevated BNP level was associated with the progression to persistent AF.

Topics: Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Disease Progression; Disease-Free Survival; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Humans; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Prevalence; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity; Stroke Volume

The practical application of elevated carbohydrate antigen 125 (CA125) to predict clinical outcome in chronic heart failure (CHF) is under debate. The mechanism for this CA125 elevation remains unknown. We hypothesize that mechanical stress on mesothelial cells initiates CA125 synthesis.. A total of 191 patients suffering from edema and/or dyspnea were enrolled. 109 patients were diagnosed as CHF, and 82 patients without CHF were assigned as control group. Echocardiography, CA125, N-terminal pro-brain natriuretic peptide (NT-proBNP), and other biochemical parameters were measured. All enrolled patients underwent heart function classification.. Patients with serous cavity effusion (SCE) demonstrated higher serum CA125 than patients without SCE (82.91 (61.90-103.92) vs. 44.98 (29.66-60.30) U/mL, P<0.001). In the absence of SCE, CA125 levels in CHF patients were slightly higher than non-CHF patients (52.37 (34.85-69.90) vs. 35.15 (23.81-46.49) U/mL, P=0.017). Additionally, compared with non-CHF patients, CHF patients had higher levels of high-sensitivity C-reactive protein (hsCRP) and lower superoxide dismutase (SOD). In all enrolled patients, CA125 levels were negatively correlated with SOD concentrations (r=-0.567, P<0.001), and positively correlated with hsCRP levels (r=0.608, P<0.001). Receiver operating characteristic curve analysis showed that CA125 was better in predicting SCE than NT-proBNP, while NT-proBNP was more suitable for predicting CHF than CA125. The in vitro study demonstrated that MUC16, the CA125 coding gene, was up-regulated by mechanical stretch on human mesothelial cell line (MeT-5A).. CA125 elevation in CHF was associated with SCE. Mechanical extension of mesothelial cells from SCE plays an important role in CA125 increase.

Topics: Aged; C-Reactive Protein; CA-125 Antigen; Chronic Disease; Electrophoresis, Agar Gel; Epithelium; Female; Heart Failure; Humans; Logistic Models; Male; Membrane Proteins; Natriuretic Peptide, Brain; Peptide Fragments; Pericardial Effusion; ROC Curve; Stress, Mechanical; Ultrasonography; Up-Regulation

The aim of this study was to define the performance of lung ultrasound (LUS) compared with clinical assessment, natriuretic peptides, and echocardiography, to evaluate decompensation in patients with systolic heart failure (HF) in an outpatient clinic.. Evaluation of pulmonary congestion in chronic HF is challenging. LUS has been recently proposed as a reliable tool for the semiquantification of extravascular lung water through assessment of B-lines.. This was a cohort study of patients with moderate to severe systolic HF. Receiver-operating characteristic (ROC) analyses were performed to compare LUS with a previously validated clinical congestion score (CCS), amino-terminal portion of B-type natriuretic peptide (NT-proBNP), E/e' ratio, chest x-ray, and 6-min walk test.. Ninety-seven patients were enrolled. Decompensation was present in 57.7% of patients when estimated by CCS, 68% by LUS, 53.6% by NT-proBNP, and 65.3% by E/e' ≥15. The number of B-lines was correlated to NT-proBNP (r = 0.72; p < 0.0001), E/e' (r = 0.68; p < 0.0001), and CCS (r = 0.43; p < 0.0001). In ROC analyses, considering as reference for decompensation a combined method (E/e' ≥ 15 and/or NT-proBNP >1,000 pg/ml), LUS yielded a C-statistic of 0.89 (95% confidence interval: 0.82 to 0.96), providing the best accuracy with a cutoff ≥ 15 B-lines (sensitivity 85%, specificity 83%). A systematic approach using CCS, E/e', NT-proBNP, chest x-ray, and 6-min walk test in different combinations as reference for decompensation also corroborated this cutoff and found a similar accuracy for LUS.. In an HF outpatient clinic, B-lines were significantly correlated with more established parameters of decompensation. A B-line ≥15 cutoff could be considered for a quick and reliable assessment of decompensation in outpatients with HF.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Cohort Studies; Echocardiography, Doppler; Exercise Test; Female; Heart Failure, Systolic; Humans; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Edema; ROC Curve

To evaluate the application value of cardiopulmonary exercise testing in patients with chronic thromboembolic pulmonary hypertension (CTEPH).. A total of 116 consecutive patients admitted into the Cardiology Department of Fuwai Hospital.They were divided into 3 groups of CTEPH (n = 44), CPE (without pulmonary hypertension in chronic pulmonary embolism) (n = 24) and control (without pulmonary embolism or pulmonary hypertension) (n = 48) respectively. Their levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Incremental cardiopulmonary exercise testing was performed to compare its differential results among 3 groups and evaluate the correlation between NT-proBNP and its parameters.. The body mass index (BMI) in the CTEPH group was lower than those in the CPE and control groups ((23.8 ± 3.9) vs (26.1 ± 3.6) and (26.7 ± 3.2) kg/m(2) ), both P < 0.05); the medical history in the CTEPH group was longer than those in the CPE and control groups ((58 ± 48) vs (12 ± 10) and (29 ± 25) months, both P < 0.05). The plasma concentrations of NT-proBNP in the CTEPH group were higher than those in the CPE and control groups ((1678 ± 1255) vs (577 ± 167) and (608 ± 247) pmol/L, both P < 0.05). All of them completed the test and there were no severe complications such as syncope or exacerbation of disease. Maximum oxygen consumption (VO2max), percentage of predicted maximum oxygen consumption (VO2 %), oxygen consumption in relation to body weight (VO2/kg), anaerobic threshold and O2 pulse in the CTEPH group were significantly lower than those in the CPE and control groups (P < 0.05). The ratios of dead space volume (VD) to tidal volume (VT) in the CTEPH and CPE groups were higher than those in the control group (P < 0.05). The plasma concentrations of NT-proBNP were inversely correlated with right ventricular internal diameter (r = -0.690, P = 0.000) and VO2/kg (r = -0.496, P = 0.000). The right ventricular internal diameter (β = 0.583, P = 0.000) and VO2/kg (β = 0.233, P = 0.032) were strong independent determinants of NT-proBNP.. As a reliable pathophysiological indictor of CTEPH, cardiopulmonary exercise testing may be used objectively and safely to evaluate the cardiopulmonary function of CTEPH patients.

Topics: Adult; Aged; Case-Control Studies; Chronic Disease; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Embolism

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥ 50 years and with ≥ 10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Interleukin-1beta; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Receptors, Interleukin-1 Type II; Serum Amyloid P-Component; Smoking; Spirometry; Ultrasonography; Ventricular Dysfunction, Left

The present study assessed the usefulness of brain natriuretic peptide in evaluating the cardiovascular status in children and grown-ups with congenital or acquired disease affected by chronic cardiac failure. Brain natriuretic peptide should be included in the risk stratification of children with dilated cardiomyopathy. In patients with congenital heart defects, it is useful to tailor the optimal medical strategy to individual patients.

Topics: Biomarkers; Chronic Disease; Echocardiography; Female; Heart Defects, Congenital; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Risk Assessment

Galectin-3 (Gal-3) is a recently discovered marker for myocardial fibrosis and elevated levels are associated with an impaired outcome after short-term follow-up in heart failure (HF) patients. However, whether Gal-3 is related to cardiac remodeling and outcome after long-term follow-up is unknown. Therefore, we determined the utility of Gal-3 as a novel biomarker for left ventricular remodeling and long-term outcome in patients with severe chronic HF.. A total of 240 HF patients with New York Heart Association (NYHA) Class III and IV were included. Patients were followed for 8.7 ± 1 years, had a mean age of 71 ± 0.6 years and 73 % of the study population was male. Circulating levels of NT-proBNP and Gal-3 were measured. Serial echocardiography was performed at baseline and at 3 months. At baseline median left ventricular end-diastolic volume (LVEDV) was 267 mL [interquartile range 232-322]. Patients were divided into three groups according to the change in LVEDV. Patients in whom the LVEDV decreased over time had significant lower levels of Gal-3 at entry compared to patients in whom the LVEDV was stable or increased (14.7 vs. 17.9 vs. 19.0 ng/mL; p = 0.004 for trend), whereas no significant differences were seen in levels of NT-proBNP (p = 0.33). Multivariate linear regression analyses revealed that Gal-3 levels were positively correlated to change in LVEDV (p = 0.007). In addition, Gal-3 was a significant predictor of mortality after long-term follow-up (p = 0.001).. Gal-3 is associated with left ventricular remodeling determined by serial echocardiography and predicts long-term mortality in patients with severe chronic HF.

Topics: Aged; Biomarkers; Chronic Disease; Female; Galectin 3; Heart Failure; Humans; Kaplan-Meier Estimate; Linear Models; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Time Factors; Ultrasonography; Ventricular Function, Left; Ventricular Remodeling

Neopterin, a marker of inflammation and monocyte activation, is found increased in patients with heart failure (HF). This study investigates whether neopterin levels correlate with left ventricular (LV) remodeling and brain natriuretic peptide (BNP), a marker of cardiac stress, in chronic HF (CHF) patients with different severity of disease.. The relationship between neopterin and LV dimensions, NT-proBNP, and pro-inflammatory cytokines were studied in 98 CHF patients, while nineteen healthy subjects were enrolled as controls. Nineteen (19%) patients were in NYHA class I, 38 (39%) in NYHA class II, 27 (28%) in NYHA class III, and 14 (14%) in NYHA class IV.. Neopterin levels were higher in CHF patients than in age- and gender-matched healthy controls, and related with indexed LV end-diastolic volume (LVEDVi). Prospectively CHF patients were separated into tertiles of low, medium and high neopterin levels. Among patients, male gender, LVEDVi, diuretic treatment, NYHA class I, NT-proBNP and IL-8 levels were significant determinants of urine neopterin levels by bivariate analysis. Neopterin levels were associated only to LV remodeling, as assessed by LVEDVi, and IL-8 levels, a crucial monocyte chemoattractant, by multivariate ordinal regression analysis.. The relationship between elevated neopterin levels and LV enlargement in CHF patients suggests a crucial role of monocyte activation in the development of cardiac dysfunction in CHF patients. Assessment of neopterin levels is a potential biomarker to evaluate the progression of LV remodeling in CHF patients.

Topics: Adult; Biomarkers; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Multivariate Analysis; Natriuretic Peptide, Brain; Neopterin; Ventricular Remodeling

Sleep-disordered breathing (SDB) deteriorates the prognosis of patients with chronic heart failure (CHF). Adaptive servo ventilation (ASV) is a new therapeutic modality to treat SDB including Cheyne-Stokes respiration associated with central sleep apnea. Renal function plays critical roles in the progression of CHF and is a strong predictor of clinical outcomes. Cystatin C is a marker of renal function, and more sensitive than serum creatinine. The purpose of the present study was to examine whether ASV is effective for cardiac overload and renal dysfunction in CHF patients with SDB. Fifty patients with CHF and SDB (mean left ventricular ejection fraction 34.0 %, estimated glomerular filtration rate (eGFR) 62.8 ml/min/1.73 cm(2)) were examined. We performed polysomnography for two consecutive days (baseline and on ASV), and measured levels of serum N terminal-pro B-type natriuretic peptide (NT-pro BNP), cystatin C, and estimated glomerular filtration rate based on cystatin C (eGFR Cyst C). ASV significantly improved the apnea hypopnea index, central apnea index, obstructive apnea index, arousal index, mean SPO2, and lowest SPO2 compared to baseline. ASV decreased NT-pro BNP (1,109.0 (2,173.2) to 912.8 (1,576.7) pg/ml, p < 0.05), cystatin C (1.391 ± 0.550-1.348 ± 0.489 mg/l, p < 0.05), and increased eGFR Cyst C (61.9 ± 30.8-65.7 ± 33.8 ml/min/1.73 cm(2), p < 0.01). ASV improved SDB, reduced cardiac overload, and ameliorated renal function in CHF patients with SDB. ASV has short-term beneficial effects on not only SDB but also cardio-renal function. ASV might be a promising useful tool for CHF as an important non-pharmacotherapy with cardio-renal protection.

Topics: Aged; Biomarkers; Cheyne-Stokes Respiration; Chronic Disease; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Respiration, Artificial; Sleep Apnea Syndromes; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1β, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF).. We studied 27 patients (15 M/12 F) with CHF, III-IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically.. CRT induced significant improvement in the NYHA class (baseline 3.2±0.5 vs. 1.0 at 12 months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12 months and the correlation with LVESV reduction was 0.41 (P=0.001).. Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.

Topics: Aged; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Case-Control Studies; Chronic Disease; Echocardiography; Extracellular Matrix; Female; Heart Failure; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Tissue Inhibitor of Metalloproteinase-2; Treatment Outcome; Ventricular Remodeling

B-type natriuretic peptide (BNP) is a useful biomarker of cardiac function in patients with mitral regurgitation (MR). However, the change in BNP in association with rhythm status after corrective surgery has not been studied.. A total of 101 patients with chronic severe MR undergoing surgery were prospectively enrolled. BNP assays and echocardiographic studies were conducted before and 6 months after surgery. Patients were divided into 3 groups according to pre- and postoperative rhythm (sinus to sinus [SS], n = 61; atrial fibrillation [AF] to sinus [AS], n = 28; AF to AF [AA], n = 12).. BNP decreased only in the AS group 6 months after mitral surgery (from 218.0 ± 136.5 to 94.7 ± 85.1 pg/mL; P < 0.001) but not in the SS or AA groups (P for interaction = 0.001). However, changes of echocardiographic parameters after surgery were not different among the 3 groups. In the AA group, postoperative left ventricular (LV) end-diastolic dimension and left atrial volume were higher than the other groups. Significant determinants of BNP were the presence of AF and the higher pulmonary artery systolic pressure preoperatively (β = 0.767 and P = 0.001 for AF; β = 0.022 and P = 0.019 for pulmonary artery systolic pressure), and the lower LV ejection fraction postoperatively (β = -0.030; P = 0.011).. After surgical correction of chronic organic severe MR, BNP decreased only in patients with preoperative AF which was converted to sinus rhythm postoperatively. A reduction in BNP was not observed when rhythm status did not change. BNP activation was associated with the presence of AF and LV systolic dysfunction, suggesting its prognostic value.

Topics: Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Rate; Heart Valve Prosthesis; Heart Ventricles; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Postoperative Period; Prognosis; Prospective Studies; Severity of Illness Index; Ventricular Function, Left

Several biomarkers are associated with mortality in hemodialysis patients. In particular, elevated cardiac troponin T and B-type natriuretic peptide (BNP) are strong predictors of mortality; however, less is known about cardiac troponin I (cTnI). Elevated troponin I is detected in many hemodialysis patients, but the association of moderate elevations with mortality is unclear.. The relation between mortality and cTnI, using a high-sensitivity cTnI assay, as well as BNP and C-reactive protein (CRP) was evaluated in 206 chronic hemodialysis patients.. Median follow-up was 28 months with a total mortality of 35%. Mortality was significantly associated with elevated cTnI, BNP and CRP. Even patients with only moderate elevation of cTnI (0.01-0.10 μg/L) showed 2.5-fold increased mortality. Interestingly, hazard ratios for mortality for single (random) measurements were comparable to those for mean/median measurements. Subsequently, subgroup analysis based on combined markers was performed. Patients with both cTnI <0.01 μg/L and BNP in the first quartile had 100% survival. Patients with either cTnI <0.01 μg/L or BNP in the lowest quartile had significantly lower mortality (12% and 13%, respectively) than patients with BNP levels in the second quartile or higher and cTnI of 0.01-0.05 μg/L and patients with cTnI ≥0.05 μg/L (mortality 46 and 58%, respectively).. A combination of moderate elevation of cTnI and BNP provided additional prognostic value. A single measurement of these biomarkers performed comparably to the mean/median of multiple measurements.

Topics: Aged; C-Reactive Protein; Chronic Disease; Female; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Renal Dialysis; Troponin I

Previous observations suggest that cardiac resynchronization therapy (CRT) may exert an anti-inflammatory effect. The objective of this study was to evaluate the effect of temporary interruption of long-term CRT on plasma concentrations of proinflammatory cytokines and brain natriuretic peptide (BNP). The study group consisted of 54 patients (32 male and 22 female, mean age 64 years) with chronic heart failure (HF) treated with CRT. BNP, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and neopterin were measured three times: after 26-28 weeks of continuous CRT (CRT-on), 48 h after its cessation (CRT-off), and 48 h after switching the CRT-on again. CRT interruption resulted in a significant worsening of left ventricular systolic function: reduction of cardiac output (CO), dP/dt, and left ventricular ejection fraction (LVEF), as well as deterioration of mitral regurgitation in the CRT responder group. A significant increase in serum concentrations of hs-CRP, neopterin, IL-6, and BNP was noted in this subpopulation. In CRT nonresponders, no significant changes were observed. In responders the changes in serum concentrations of hs-CRP, IL-6, neopterin, and BNP, following CRT interruption, significantly correlated with the respective changes in thoracic fluid content (TFC) and inversely correlated with LVEF changes. Even short (48 h) interruption of long-term CRT led to a significant increase of proinflammatory cytokines and BNP concentrations in responders. The changes in hs-CRP, IL-6, neopterin, and BNP concentrations correlated with the change in TFC-marker of pulmonary congestion and inversely correlated with the change in LVEF.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiac Resynchronization Therapy; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Neopterin; Stroke Volume; Time Factors; Treatment Outcome; Up-Regulation; Ventricular Function, Left

Baseline values, serial measurements, or both of multiple biomarkers (copeptin, a peptide co-secreted with arginine vasopressin; hyponatremia; B-type natriuretic peptide [BNP]; and cardiac troponin T [cTnT]) may improve risk stratification in outpatients with chronic heart failure. A cohort of 157 patients with class III or IV heart failure was prospectively evaluated every 3 months over 2 years with regard to biomarker levels and risk for death or cardiac transplantation. Copeptin ≥40 pmol/L (cohort fourth quartile value), hyponatremia (≤135 mEq/L), BNP >3 times the upper range limitation of normal adjusted for age and gender, and cTnT ≥0.01 ng/ml were pre hoc determined cut points. After multivariate time-dependent regression analysis, copeptin (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.2 to 4.3, p = 0.014) and BNP (HR 1.89, 95% CI 1.0 to 3.5, p = 0.047), but not hyponatremia, were associated with the primary end point of death or cardiac transplantation. In contrast to univariate prediction of mortality and transplantation, hyponatremia (HR 1.74, 95% CI 0.9 to 3.4, p = 0.099) and cTnT ≥0.01 ng/ml (HR 1.89, 95% CI 1.0 to 3.7, p = 0.064) were not predictive in multivariate models. Interaction models of copeptin with hyponatremia, adjusted for BNP and cTnT, improved the predictive capacity of serial measurements (HR 4.20, 95% CI 1.6 to 8.9, p = 0.004). In conclusion, marked elevations of copeptin, particularly in serial measurements, are independent predictors of poor outcomes. The combination of elevated copeptin with hyponatremia, when adjusted for BNP and cTnT, is an even stronger predictor. These markers appear to reflect activation of the arginine vasopressin system present even in the absence of overt clinical changes. A strategy of serial monitoring of copeptin in combination with hyponatremia may be valuable in identifying higher risk patients with heart failure.

Topics: Aged; Biomarkers; Chi-Square Distribution; Chronic Disease; Female; Glycopeptides; Heart Failure; Heart Transplantation; Humans; Hyponatremia; Male; Natriuretic Peptide, Brain; Proportional Hazards Models; Prospective Studies; Risk Factors; Survival Rate; Troponin T

The aim of this study was to assess the relation between inferior vena cava (IVC) diameter, clinical variables, and outcome in patients with chronic heart failure (HF).. The IVC distends as right atrial pressure rises. Therefore it might represent an index of HF severity independent of left ventricular ejection fraction (LVEF). The relation between IVC diameter and other clinical variables and its prognostic significance in patients with HF has not been explored.. Outpatients attending a community HF service between 2008 and 2010 were enrolled. Heart failure was defined as the presence of relevant symptoms and signs and objective evidence of cardiac dysfunction: either LVEF <45% or the combination of both left atrial dilation (≥4 cm) and raised amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml. Patients were followed for a median of 567 (interquartile range: 413 to 736) days. The primary composite endpoint was cardiovascular death and HF hospitalization.. Among the 693 patients enrolled, median age was 73 years, 33% were women, and 568 had HF. Patients with HF in the highest tertile of IVC diameter were older; had lower body mass index; were more likely to have atrial fibrillation and to be treated with diuretics; and had larger left atrial volumes, higher pulmonary pressures, and less negative values for global longitudinal strain. The LVEF and systolic blood pressure were similar across tertiles of IVC diameter. The IVC diameter and log [NT-proBNP] were correlated (r = 0.55, p < 0.001). During follow-up, 158 patients reached a primary endpoint. In a multivariable Cox regression model, including NT-proBNP, only increasing IVC diameter, urea, and the trans-tricuspid systolic gradient independently predicted a poor outcome. Neither global longitudinal strain nor LVEF were adverse predictors.. In patients with chronic HF with or without a reduced LVEF, increasing IVC diameter identifies patients with an adverse outcome.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Chi-Square Distribution; Chronic Disease; Community Health Services; Female; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ultrasonography; Vena Cava, Inferior; Ventricular Function, Left

Tricuspid regurgitation (TR) is common in patients with chronic heart failure (CHF) but its prognostic impact is unclear.. A total of 576 consecutive patients with CHF were prospectively included. The impact of moderate and severe (significant) TR on the combined endpoint death/heart transplantation/left ventricular-assist device implantation was assessed. Patients were followed for 5.8 ± 4.2 (maximum 14.4) years. Kaplan-Meier analysis showed a worse outcome of patients with significant TR (P < 0.0001). By multivariable analysis, amino terminal pro B-type natriuretic peptide (NT-proBNP) (P = 0.0028), systolic left ventricular function (LVF) (P = 0.0014), serum sodium, NYHA functional class, systolic blood pressure, right atrial size (all P = 0.0001), but not TR were significantly related with the outcome. However, as soon as the strong interaction between TR and LVF was included in the model, significant TR determined outcome as well (P = 0.0059). Therefore, in a second analysis patients were stratified for LVF. In patients with mildly or moderately impaired LVF, TR was significantly related with the outcome (HR: 1.368, CI: 1.070-1.748, P = 0.0125), whereas in patients with severely depressed LVF it was not (P = 0.1401). As a proof of concept, we additionally stratified patients according to serum NT-proBNP concentrations. In patients with NT-proBNP concentrations below the median (≤ 280 fmol/mL), TR was related with the outcome (HR: 2.512, CI: 1.127-5.597, P = 0.0242) but it was not in patients with NT-proBNP concentrations above the median (P = 0.3935).. The prognostic impact of TR depends on the severity of CHF. While TR was significantly related with excess mortality in mild to moderate CHF, it provided no additive value in advanced disease when compared with established risk factors.

Topics: Chronic Disease; Electrocardiography; Female; Heart Failure, Systolic; Heart Transplantation; Heart-Assist Devices; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Tricuspid Valve Insufficiency

In patients with chronic heart failure, physical evaluation and clinical judgment may be inadequate for prognostic stratification.. Information obtained with simple bedside tests would be helpful in patient management.. We report on 142 outpatients with systolic heart failure seen at our heart failure unit from 2007 to 2010 (ages 69.4 ± 8.9 years; ejection fraction [EF] 30.6 ± 6.1%; 43% with implanted defibrillators and/or resynchronization devices). At their first visit, we assessed levels of brain natriuretic peptide (BNP) (pg/mL), evaluated transthoracic conductance (TFC) (1/kΩ) by transthoracic bioimpedance, and performed echocardiography.. Four-year mortality was 21.2%. At multivariate analysis, surviving and deceased subjects did not differ regarding New York Heart Association, age, gender, heart failure etiology, or EF at index visit. Patients who died had higher BNP and TFC (BNP = 884 ± 119 pg/mL vs 334 ± 110 pg/mL; TFC = 50 ± 8/kΩ vs 37 ± 7/kΩ, both P < 0.001]. Patients with BNP < 450 pg/mL and TFC < 40/kΩ had a 2.1% 4-year mortality, compared to 46.5% mortality of patients having BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ. BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ showed high sensitivity (91%) and specificity (88%)in identifying patients who died at follow-up.. The combined use of BNP and impedance cardiography during the first assessment of a patient in a heart failure unit identified those carrying a worse medium-term prognosis. This approach could help the subsequent management of patients, allowing better clinical and therapeutic strategies.

Topics: Aged; Ambulatory Care; Biomarkers; Cardiography, Impedance; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Factors; Stroke Volume; Time Factors; Ventricular Function, Left

The article discusses the results of detection of activity of matrix metalloproteinase-9, tissue inhibitors of metalloproteinases-4, endotoxin, tumor necrosis factor-alpha, C-reactive protein, sE-selectine in blood of patients with chronic cardiac failure depending on severity of disease. It is demonstrated that progressing of chronic cardiac failure is associated with the increase of level of endotoxemia, activation of systemic inflammation and misbalance in the system of matrix metalloproteinase and tissue inhibitors of metalloproteinase.

Topics: C-Reactive Protein; Chronic Disease; Endotoxins; Female; Heart Failure; Humans; Inflammation; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factor-alpha

Altered myocardial extracellular matrix turnover has been proposed as a major determinant of myocardial remodelling. Carboxy-terminal telopeptide of collagen type-I (CITP) represents a collagen type-I degradation-derived serum peptide. In this study we examined the independent and additive prognostic value of serum concentrations of CITP compared with well-known mortality predictors such as the N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients.. We studied 196 consecutive patients (126 male, mean age 69 ± 10 years), who were admitted for acute decompensation of the CHF syndrome. The study entry point was determined at the discharge of the patients after achieving a stable compensated status. The primary endpoint was cardiac mortality during a 12-month follow-up.. In the multivariate Cox proportional hazard model the levels of CITP remained a predictor of survival (hazards ratio 0.4 95% confidence interval 0.21-0.76, P = 0.005), independent of NT-proBNP levels. The stratified log-rank test (P < 0.001) showed that CHF patients characterized by low levels of both biomarkers had better survival (hazards ratio 0.12 95% confidence interval 0.04-0.35, P < 0.001) compared with patients characterized by high levels of both biomarkers. The negative predictive value of the combined measure for long-term adverse events was 94%.. Serum levels of CITP were shown to be an independent and strong prognostic marker regarding survival in CHF patients. Furthermore, CITP levels had an additive prognostic value compared with NT-proBNP levels. These findings underline the detrimental role of myocardial fibrosis in the progression of heart failure and suggest a novel multi-marker approach for risk stratification in the CHF syndrome.

Topics: Aged; Biomarkers; Chi-Square Distribution; Chronic Disease; Collagen Type I; Disease Progression; Disease-Free Survival; Female; Fibrosis; Greece; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Sensitivity and Specificity; Time Factors

We investigated whether dobutamine-induced changes of the left atrial (LA) two-dimensional speckle tracking parameters are related to clinical and neurohumoral improvement after levosimendan treatment in patients with acutely decompensate chronic heart failure (ADCHF).. Forty-six patients with ADCHF and LV ejection fraction <35%, were studied using dobutamine stress echocardiography before a 24-hour infusion of levosimendan. In a multivariable model, we included: dobutamine-induced LV contractile reserve, change (%) of LA volume, LV longitudinal strain rate and LA speckle tracking parameters to assess the improvement of NYHA class, 6-min walk distance and brain natriuretic peptide (BNP).. The change (%) of LA-contractile strain and LV longitudinal stain rate were independent determinants of improvement of NYHA class, and BNP and increase in the 6-min walk test distance (b=-0.59, b=-0.65, b=0.41, and b=-0.44, b=-0.40, b=0.60, respectively, p<0.05). The addition of LA-contractile strain change in the multivariable analysis including LV longitudinal stain rate change increased the value of the model from r(2)=0.46 to 0.58 for NYHA improvement and from r(2)=0.44 to 0.70, for the BNP reduction and from r(2)=0.49 to 0.60, for increase in the 6-min walk test distance (p<0.05). The change (%) of LA-reservoir strain was univariate determinant for increase in the 6-min walk test distance (b=-0.37, p=0.02) and increased the value of the multivariate model from r(2)=0.46 to 0.58, p=0.02.. In patients with ADCHF, left atrial two-dimensional speckle tracking parameters in addition to LV longitudinal strain rate may detect those patients who are prone to improve after levosimendan treatment.

Topics: Aged; Atrial Function, Left; Biomarkers; Chronic Disease; Dobutamine; Echocardiography; Echocardiography, Stress; Female; Forecasting; Heart Failure; Humans; Hydrazones; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Pyridazines; Simendan; Treatment Outcome

Plasma BNP and NT-proBNP are often used as interchangeable parameters in heart failure care in clinical practice. In our previous study we have shown that inflammation was able to induce increased NT pro BNP in a hospital cohort with chronic heart failure in the elderly, indicating that NT-proBNP/BNP ratio should be evaluated concomitantly with inflammatory status to avoid overestimation of heart failure severity. The present study was aimed to evaluate the clinical significance of NT-proBNP/BNP ratio in comparison with NTpro BNP or BNP alone as a prognostic indicator in a 2-year follow up of elderly heart failure population.. One hundred and eight-nine elderly heart failure patients (72 ± 11 years, male 52%, LVEF 46 ± 14%) were enrolled consecutively during 2006 and 2007 and followed up during 2 years. NTpro BNP and BNP were measured routinely.. We have found that NTpro BNP/BNP ratio provides no additional prognostic information during follow up as compared to NTpro BNP or BNP alone in an elderly population with chronic heart failure. By the use of ROC curves, for total mortality predictive accuracy during 2 years, the cut-off values are NTproBNP ≥ 800 pg/ml, BNP > 60 pg/ml and NTpro BNP/BNP ratio>6.4 respectively. In terms of NTpro BNP, as long as its serum level is above 2000 pg/ml it indicates poor prognosis. However there is an overlap between serum concentration range 2000-8000 pg/ml and >8000 pg/ml in terms of prognostic indicator. Similarly for BNP, as long as its serum level is above 100 pg/ml, it indicates poor prognosis. However there is an overlap between serum concentration range 100-800 pg/ml and >800 pg/ml in terms of prognostic indicator. There was significant correlation between survival and NTpro BNP, BNP and Cystatin-C but not with NTpro BNP/BNP ratio. Such correlation exists irrespective of subgroups regardless of less than or older than 70 years old.. Our results demonstrated that in elderly heart failure population NTpro BNP/BNP ratio may provide diagnostic help in the presence of acute infection but no additional prognostic information in the long run as compared with NTpro BNP or BNP alone. Furthermore, both NTpro BNP and BNP are useful prognostic biomarkers indeed but they need to be interpreted with caution when it is used as a single biomarker and in the meantime concomitant diseases exist because patients may die due to non-cardiac causes.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

B-type natriuretic peptide level is increased in patients with atrial fibrillation. The aim of the present study was to present the distribution of steady-state B-type natriuretic peptide levels of various clinical backgrounds and to elucidate the usefulness of measuring them in patients with atrial fibrillation. B-type natriuretic peptide was measured in stable conditions in patients with atrial fibrillation (74 ± 10 y/o, n = 473). The average B-type natriuretic peptide level was 161 ± 202 (median 101) pg/ml. Multiple regression analysis showed that age, left ventricular ejection fraction, left atrial diameter, structural heart disease, chronic atrial fibrillation, and heart failure symptoms were independently associated with elevated B-type natriuretic peptide levels. However, in chronic atrial fibrillation patients without structural heart disease, B-type natriuretic peptide levels did not differ between those with and without heart failure symptoms. Notably, B-type natriuretic peptide levels were high (≥ 150 pg/ml) in 41% of asymptomatic chronic atrial fibrillation without structural heart disease. Steady-state B-type natriuretic peptide levels of various clinical backgrounds were presented. Contributions of BNP elevation by clinical variables were somewhat different in different population. B-type natriuretic peptide was elevated in substantial percentage of asymptomatic chronic atrial fibrillation even without structural heart disease.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Chi-Square Distribution; Chronic Disease; Female; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Regression Analysis; Retrospective Studies; ROC Curve; Up-Regulation; Young Adult

Kidney donors are a chronic kidney disease (CKD) cohort virtually guaranteed to have a low risk of CKD progression, as they are screened for CKD risk factors beforehand. However, there has been no evidence of cardiovascular disease (CVD), which is an outcome of CKD, for these donors. In this study, the conditions of CKD in kidney donors were investigated and the risk of CVD was estimated using nephrectomy patients, who are thought to have a crude risk of CKD progression, as a model. In 86 kidney donors, estimated glomerular filtration rates (eGFR) were measured, and they were classified according to the CKD stage. Plasma brain natriuretic peptide (BNP) concentrations and urinary albumin (mg/g Cre) levels were also measured as markers for cardiovascular evaluation. A total of 200 nephrectomy patients were similarly classified according to the CKD stage. A multivariate regression analysis was carried out to evaluate the risk factors of CVD. Among the kidney donors, 4.9% were CKD stage 1, 24.6% stage 2 and 70.5% stage 3. Among the nephrectomy patients, 20.5% were CKD stage 2, 66.6% stage 3, 9.5% stage 4 and 3.4% stage 5. Plasma BNP concentrations of the donors were significantly higher compared to those of healthy volunteers (24.5±24.9 vs. 8.6±7.6 pg/ml, p<0.0001). In addition, approximately 16% of the donors had microalbuminuria and 4% had overt proteinuria. The prevalence of new-onset CVD was 2.3% for the donors and 10% for the nephrectomy patients (p=0.0281). By logistic regression analysis of the nephrectomy patients, proteinuria, age and hypertension were significantly independent risk factors for new-onset CVD. Our findings suggest that the risks of CVD may be increased in kidney donors. In our analysis of new-onset CVD in nephrectomy patients, proteinuria, age and hypertension were significantly related factors. This suggests that in the follow-up of kidney donors, those who present these conditions from before or during follow-up should be carefully monitored.

Topics: Adult; Age Factors; Albuminuria; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nephrectomy; Odds Ratio; Prevalence; Proteinuria; Risk Factors; Serum Albumin; Tissue Donors

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment.. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment.. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Death, Sudden, Cardiac; Deoxyguanosine; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Propanolamines; Prospective Studies; Risk Factors; Treatment Outcome

Exercise intolerance predicts mortality in patients with chronic heart failure (CHF). Recently, increased red cell distribution width (RDW) has emerged as an additional powerful predictor of poor outcome. We investigated the relationship between RDW and exercise capacity in patients with CHF. In addition, the association between training-induced improved maximal aerobic capacity (VO(2)peak) and RDW was studied.. Stable and optimally treated CHF patients (n = 118) with a left ventricular ejection fraction (LVEF) <40% were included. RDW and cardiopulmonary exercise testing were obtained at baseline and after 6 months of exercise training (n = 71) or a sedentary lifestyle (n = 47). At baseline, log[RDW] was inversely related to VO(2)peak (P = 0.003), independently of disease severity [LVEF, New York Heart Association class, N-terminal pro brain natriuretic peptide (NT-proBNP)] and haemoglobin. Exercise training was associated with a decrease in RDW compared with controls (P < 0.0001 for interaction), independent of baseline VO(2)peak, haemoglobin, and NT-proBNP levels. The change in RDW after 6 months was significantly related to the change in VO(2)peak (r= -0.248, P = 0.009).. Higher RDW is independently related to impaired exercise capacity in CHF patients. Increased VO(2)peak following exercise training relates to the observed changes in RDW. Whether increased RDW is a marker of impaired exercise tolerance, or plays a pathophysiological role in impaired oxygen transport, deserves further investigation.

Topics: Aged; Chronic Disease; Erythrocyte Indices; Exercise Movement Techniques; Exercise Tolerance; Female; Heart Failure; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Physical Fitness; Predictive Value of Tests; Severity of Illness Index; Stroke Volume

The left ventricular (LV) scar size detected by cardiac magnetic resonance (CMR) imaging in ischemic cardiomyopathy (IC) has been correlated with mortality. However, the associations among myocardial fibrosis, ventricular geometry, and physiologic measures of myocardial performance remain to be defined. A retrospective analysis of patients with stable chronic IC (LV ejection fraction ≤50%) who underwent CMR imaging from 2004 to 2010 and had plasma B-type natriuretic peptide (BNP) measured within 14 days of the CMR study was undertaken. A total of 38 patients met the criteria (mean age 66 ± 10 years; 31 men [82%]). The duration of IC was 67 ± 69 months. The CMR characteristics included LV dilation (LV end-diastolic dimension 62 ± 8 mm) and severe systolic dysfunction (LV ejection fraction 28 ± 11%). The average quantitated myocardial fibrosis was 20 ± 12% of the LV mass. When stratified by fibrotic mass, increased myocardial scar size was associated with increased LV cavity size (p = 0.007), lower LV ejection fraction (p = 0.04), and higher BNP (p = 0.013). In comparison, when stratified by median BNP (475 pg/ml), an elevated BNP level was associated, not only with LV size, function, and degree of fibrosis, but also with increased meridional wall stress (p = 0.002) and worse New York Heart Association functional class (p = 0.006). In conclusion, in chronic IC, quantitated myocardial fibrosis is associated with CMR structural and functional LV abnormalities. Elevated BNP levels are related to high-risk structural and functional CMR abnormalities and wall stress and functional status. Myocardial fibrosis appears to be related to plasma BNP through the processes of ventricular remodeling.

Topics: Aged; Cardiomyopathies; Chronic Disease; Diagnosis, Differential; Disease Progression; Female; Fibrosis; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Severity of Illness Index; Ventricular Remodeling

Diagnosis and risk stratification of patients with heart failure remain a challenge. The small non-coding RNAs known as microRNAs regulate gene expression and seem to play an important role in the pathogenesis of heart failure. In the current study, we aim to characterize the levels of microRNAs in the sera of chronic systolic heart failure patients vs. controls and assess the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in heart failure patients.. The levels of 186 microRNAs were measured in the sera of 30 stable chronic systolic heart failure patients and 30 controls using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The differences in microRNA levels between the two groups were characterized, and a score, based on the levels of four specific microRNAs with the most significant increase in the heart failure group (miR-423-5p, miR-320a, miR-22, and miR-92b), was defined. The score was used to discriminate heart failure patients from controls with a sensitivity and specificity of 90%. Moreover, in the heart failure group, there was a significant association between the score and important clinical prognostic parameters such as elevated serum natriuretic peptide levels, a wide QRS, and dilatation of the left ventricle and left atrium (r = 0.63, P = 3e-4; P = 0.009; P = 0.03; and P = 0.01, respectively).. Elevated serum levels of specific microRNAs: miR-423-5p, miR-320a, miR-22, and miR-92b, identify systolic heart failure patients and correlate with important clinical prognostic parameters.

Topics: Aged; Chronic Disease; Female; Heart Failure, Systolic; Humans; Male; MicroRNAs; Middle Aged; Natriuretic Peptide, Brain; Prognosis

Heart Failure (HF) is characterized by activation inflammatory mediators that contributes to the disease progression. Brain natriuretic peptide (BNP) plasma levels increase in HF with a prognostic significance. The aim of this study was to evaluate the expression and activity of inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cell (PBMC) extracted from patients and a possible linear correlation between iNOS and plasma levels of BNP in decompensated chronic HF (DCHF) patients. To establish the DCHF, thirty-five male patients were evaluated. All patients were venesected within 24 h of admission to exclude an inflammatory state through evaluation of c-reactive protein. Only twenty subjects showed symptoms of DCHF were included in the study. Other patients were included in the control group. In DCHF, left ventricular ejection fraction (LVEF) percent was reduced and systolic pulmonary artery pressure (PAPs) was increased. Furthermore, iNOS expression and BNP plasma levels were significantly higher in patients with DCHF as compared to controls group. These findings indicate that in DCHF patients, iNOS activity exhibits a significant linear correlation with plasmatic BNP level.

Topics: Aged; Chronic Disease; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type II

Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT).. Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables.. Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT.. Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials.

Topics: Adult; Biomarkers; C-Reactive Protein; Chronic Disease; Female; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prognosis; Proportional Hazards Models; Registries; Risk Assessment; Risk Factors; Severity of Illness Index; Survival Rate; Time Factors; Waiting Lists

The presence of heart failure (HF) with preserved ejection fraction (HFPEF) is increasingly recognized. However, prognostic factors for HFPEF remain unclear.. The data were derived from Shinken Database 2004-2010, a prospective cohort study (n=15,227). We examined 301 consecutive HFPEF patients (New York Heart Association Class II or greater) and tracked them for an average 3.5 years. Cardiopulmonary exercise testing (CPX), blood exams, and ultrasound cardiogram (UCG) were performed at the first medical examination. Acute decompensated HF (ADHF) admission was observed in 19 patients (6.3%). CPX showed that the anaerobic threshold was lower (7.3±4.8mL/min/kg vs. 9.7±4.3mL/min/kg, p=0.02) and slope of the increase in ventilation to the increase in CO(2) output (VE-VCO(2) slope) was higher (40.6±8.5 vs. 34.6±7.9, p<0.01) in patients with ADHF admission than those without. Serum brain natriuretic peptide (BNP) tended to be higher and left atrial (LA) dimension was significantly greater (47.0±15.8mm vs. 41.0±9.9mm, p=0.01) in patients with ADHF admission than those without. Multivariate analysis showed that higher VE-VCO(2) slope and greater LA dimension were independent determinants of ADHF admission.. An aggravated CPX parameter and LA dilatation were associated with ADHF admission in patients with symptomatic HFPEF, suggesting the prognostic role of cardiopulmonary dysfunction during exercise and LA remodeling in the pathogenesis of decompensated HF development in HFPEF.

Topics: Acute Disease; Aged; Aged, 80 and over; Anaerobic Threshold; Biomarkers; Chronic Disease; Cohort Studies; Exercise Test; Female; Heart Atria; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Stroke Volume

To investigate the feasibility of applying (1)H-NMR-based pattern recognition in the studies of serum metabonomics in chronic heart failure (HF).. (1)H-NMR technique was applied for examination of the serum samples from 9 patients with chronic heart failure and 6 healthy individuals. The data were analyzed for pattern recognition through principal component analysis (PCA) and Orthogonal Partial Least Square (OPLS) to determine the differences in serum metabolites between the two groups. The recognition ability of the two analysis methods were compared.. The serum (1)H-NMR spectra of heart failure patients and healthy individuals were significantly different. The PCA method failed to distinguish the patterns between the two groups, but OPLS clearly differentiated the two groups.. (1)H-NMR technique is effective in the study of serum metabolomics in chronic heart failure. The serum metabonomics of patients with chronic heart failure and the healthy individuals are significantly different. OPLS pattern recognition method is superior to PCA method in that the former can remove the influence of non-experimental factors and provide an improved characterization.

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Least-Squares Analysis; Magnetic Resonance Spectroscopy; Male; Metabolome; Metabolomics; Middle Aged; Natriuretic Peptide, Brain; Pattern Recognition, Automated; Principal Component Analysis; Uric Acid

B-type natriuretic peptide (BNP) levels provide diagnostic and prognostic information in heart failure. This study determined the frequency of BNP assessment and analyzed demographic characteristics, clinical variables and the utilization of guideline-recommended heart failure therapies by BNP level in outpatients with reduced left ventricular ejection fraction (LVEF).. The IMPROVE HF registry (The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting) is a prospective cohort study of patients at least 18 years of age with a LVEF 35% or less and chronic heart failure or previous myocardial infarction (MI) presenting to cardiology and multispecialty practices. The medical records of 15,381 patients were reviewed. BNP was measured in 4213 (27.4%) patients and the median plasma BNP level was 384 pg/ml (interquartile range 158-877 pg/ml). Patients were stratified by plasma BNP measurements into the following tertiles: 219 pg/ml or less, more than 219 to 649 pg/ml, and more than 649 pg/ml. Jugular venous distension, pedal edema, rales and systolic murmur on physical examination and elevated renal function parameters were associated with higher BNP levels. BNP assessment and elevated BNP levels were not associated with greater use of any of the quality of care measures. However, patients with a BNP in the top tertile were less likely to be treated with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or aldosterone antagonists compared with patients with a BNP in the bottom tertile.. Among practices participating in IMPROVE HF, BNP was not measured in most outpatients with reduced LVEF and chronic heart failure or previous MI. BNP assessment or the BNP level in patients with recorded measurements, with few exceptions, did not impact the utilization of guideline-recommended therapies.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Chronic Disease; Cohort Studies; Female; Guideline Adherence; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Prognosis; Prospective Studies; Registries; Stroke Volume; Ventricular Function, Left

Topics: Biomarkers; Chronic Disease; Heart Failure; Natriuretic Peptide, Brain; Peptide Fragments

Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95% confidence interval 0.9 to 2.4, p = 0.16) for quartile 2, 1.7 (0.9 to 2.5, p = 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4 and 1.7 (1.2 to 2.5, p = 0.003) for abnormal versus normal level of hs-cTnT. In patients without CAD, quartile 4 of hs-cTnT was associated with an adjusted hazard ratio of 6.8. In conclusion, hs-cTnT is increased in most outpatients with chronic systolic HF and carries prognostic information beyond clinical parameters and amino-terminal pro-B-type natriuretic peptide. Increased hs-cTnT indicated a particularly deleterious prognosis in patients without CAD.

Topics: Aged; Aged, 80 and over; Chronic Disease; Cohort Studies; Coronary Artery Disease; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke Volume; Survival Rate; Troponin T; Ventricular Dysfunction, Left

Heart failure still maintains a high mortality. Biomarkers reflecting different pathophysiological pathways are under evaluation to better stratify the mortality risk. The objective was to assess high-sensitivity cardiac troponin T (hs-cTnT) in combination with N-terminal pro-B type natriuretic peptide (NT-proBNP) for risk stratification in a real-life cohort of ambulatory heart failure patients.. We analyzed 876 consecutive patients (median age 70.3 years, median left ventricular ejection fraction 34%) treated at a heart failure unit. A combination of biomarkers reflecting myocyte injury (hs-cTnT) and myocardial stretch (NT-proBNP) was used in addition to an assessment based on established mortality risk factors (age, sex, left ventricular ejection fraction, New York Heart Association functional class, diabetes, estimated glomerular filtration rate, ischemic etiology, sodium, hemoglobin, β-blocker treatment, and angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment).. During a median follow-up of 41.4 months, 311 patients died. In the multivariable Cox proportional hazards model, hs-cTnT and NT-proBNP were independent prognosticators (P = .003 each). The combined elevation of both biomarkers above cut-off values significantly increased the risk of death (HR 7.42 [95% CI, 5.23-10.54], P < .001). When hs-cTnT and NT-proBNP were individually included in a model with established mortality risk factors, measurements of performance significantly improved. Results obtained for hs-cTnT compared with NT-proBNP were superior according to comprehensive discrimination, calibration, and reclassification analysis (net reclassification indices of 7.7% and 1.5%, respectively).. hs-cTnT provides significant prognostic information in a real-life cohort of patients with chronic heart failure. Simultaneous addition of hs-cTnT and NT-proBNP into a model that includes established risk factors improves mortality risk stratification.

Topics: Age Factors; Aged; Biomarkers; Chronic Disease; Cohort Studies; Confidence Intervals; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Sex Factors; Survival Analysis; Troponin T

Anemia is common in patients with chronic heart failure (CHF) and is associated with a worse prognosis. This study aims to identify the biological mechanisms which reflect evolutionary changes in the hemoglobin concentrations in heart failure patients who are still not anaemic.. Fifty-nine patients (54 ± 14 years, 83% males) with CHF (LVEF 28 ± 10%), who did not have anemia, and had not received any previous transfusions, were included. The parameters studied were: iron metabolism (ferritin, iron, transferrin, soluble transferrin receptor (sTfR), hepcidin); inflammation (C-reactive protein, soluble TNFα receptor I (sTNFRI), interleukin 6); and myocardial stress (NT-proBNP, high sensitivity TnT, growth differentiation factor 15). All parameters were measured on inclusion and 1 year after inclusion.. Baseline hemoglobin (g/dL) was 14.7 ± 1.5 and at 1 year of follow-up it showed a significant decrease of -0.4 (RIC: -0.7 to -0.06) (p=0.02). At baseline, only the sTNFRI was a predictor of a decrease in hemoglobin 1 year later (p=0.007). During follow-up, the increase in sTNFRI (p=0.002, r=-0.39) and hepcidin (p=0.006, r=-0.35) were both associated with a decrease in hemoglobin. Similarly, the patients who became anemic (13%) had higher levels of hepcidin (p=0.001) and sTNFRI (p=0.008). The remaining parameters did not show any relationship with the evolution in the hemoglobin.. In CHF patients without anemia, the increase in the inflammatory state (sTNFRI) and the following deterioration in the iron metabolism (hepcidin) were the main determinants of a decrease in hemoglobin and the appearance of anemia in the long term follow-up period.

Topics: Adult; Aged; Anemia; Antimicrobial Cationic Peptides; Chronic Disease; Female; Follow-Up Studies; Growth Differentiation Factor 15; Heart Failure; Hemoglobins; Hepcidins; Humans; Iron Deficiencies; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Receptors, Tumor Necrosis Factor, Type I; Stroke Volume; Troponin T

It has been suggested that troponins and natriuretic peptides can be falsely elevated in subjects with impaired kidney function because of decreased renal clearance. The value of these biomarkers in subjects with impaired kidney function has therefore been debated. We tested in a population-based cohort study, first, whether high-sensitive troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels are cross-sectionally associated with the estimated glomerular filtration rate (eGFR) and albuminuria, and secondly, whether these markers are associated with cardiovascular outcome, independent of eGFR, albuminuria and conventional cardiovascular risk factors.. We included 8121 subjects from the PREVEND study with both values of hsTnT and NT-pro-BNP available. High-sensitive troponin T >0.01 µg/L and NT-pro-BNP >125 ng/L were defined as elevated. We first performed linear regression analyses with hsTnT and NT-pro-BNP as dependent variables. Next, we performed Cox-regression analyses, studying the associations of hsTnT and NT-pro-BNP with incident cardiovascular events. Of our cohort, 6.7% had an elevated hsTnT and 12.2% an elevated NT-pro-BNP. Also, the estimated glomerular filtration rate, albuminuria, and ECG-assessed ischaemia and left ventricular hypertrophy were all significantly associated with hsTnT and NT-pro-BNP in the linear regression analyses. Both hsTnT and NT-pro-BNP appeared associated with cardiovascular events, and these associations remained significant after adjustment for eGFR, albuminuria, age, gender and conventional cardiovascular risk factors (P= 0.03 and P< 0.001, respectively). Only a few subjects with markedly reduced renal function were included. The results presented are therefore mainly valid for a population with mildly impaired renal function.. These data indicate that a finding of an increased hsTnT or NT-pro-BNP in subjects with chronic kidney disease stages 1/3 should be taken seriously as a prognostic marker for a worse cardiovascular outcome and not be discarded as merely a reflection of decreased renal clearance.

Topics: Adult; Aged; Albuminuria; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin T

The objective of this paper was to investigate the diagnostic and prognostic value of plasma B type natriuretic peptide (BNP) and serum triiodothyronine (T3) in chronic congestive heart failure (CHF).. 156 cases of CHF patients and 75 cases of cardiac function I patients hospitalized over the same period were utilized in this study. On admission, the patient's BNP and T3 plasma concentrations were measured. The correlation analysis of plasma BNP and T3 in CHF patients with cardiac function classification was conducted.. According to the NYHA grading systems, the plasma BNP levels in patients with II, III, and IV grade CHF were significantly higher than those with cardiac function I (P < 0.05); BNP levels and NYHA grading of cardiac function correlated positively. The BNP concentrations increased with CHF progression (P < 0.01). The T3 level and NYHA grading of cardiac function correlated negatively.TheT3 level decreased as the degree of heart failure increased. Using CHF in combination with BNP to predict the occurrence of CHF had a sensitivity value of 90.8% with 95.5% specificity, 86.3% accuracy, and a negative predictive value of 87.7%.. Plasma BNP was more sensitive than T3 in the diagnosis of CHF. The T3 was more meaningful than the BNP in the prognosis of CHF. The BNP and T3 combination detection was more valuable in determining the severity of CHF and prognosis.

Topics: Aged; Analysis of Variance; Chi-Square Distribution; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Triiodothyronine

Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect, and cystatin C (CysC) is promoted as a better marker of glomerular filtration rate. This study compares the prognostic use of CysC and derived glomerular filtration rate estimates with other measures of renal function in patients with chronic heart failure.. We measured serum CysC levels in 823 patients with heart failure undergoing coronary angiography with follow-up of major adverse cardiovascular events (death, myocardial infarction, stroke). CysC levels strongly correlated with creatinine (r=0.73), blood urea nitrogen (r=0.70), and estimated glomerular filtration rate by the 4-variable modification of diet in renal disease equation (r=-0.62) (all P<0.001). However, the correlation was lower in estimated glomerular filtration rate ≥60 mL/min per 1.73 m(2). CysC-based measures significantly improved areas under the receiver operating characteristic curve for the prediction of major adverse cardiovascular events, especially in estimated glomerular filtration rate ≥60 mL/min per 1.73 m(2) (P<0.01). Net reclassification improvement was 22.2% (P<0.001) in this group. CysC remained an independent predictor of major adverse cardiovascular events (P<0.001) after adjustment for traditional risk factors and brain natriuretic peptide.. CysC is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with preserved renal function.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Chronic Disease; Coronary Angiography; Cystatin C; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney; Male; Middle Aged; Models, Biological; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Ohio; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke

To study the prognostic value of therapy-induced changes in plasma NT-proBNP levels in patients with left ventricular (LV) systolic dysfunction.. The study covered 84 patients aged 23 to 70 years (mean 54 +/- 8.1 years) with LV systolic dysfunction (an ejection fraction of < 40%). Plasma NT-proBNP levels were determined in all the patients at baseline and 3 months later to evaluate the efficiency of therapy for heart failure (HF). The median follow-up was 18 months. The follow-up recorded the following outcomes (end points): death from decompensated HF and unplanned hospital admissions for progressive HF symptoms.. The baseline and therapy high plasma levels of NT-proBNP (more than 3000 pg/ml) were associated with worsening prognosis. The therapy-induced decrease in NT-proBNP levels was associated with more favorable prognosis.. Repeat dynamic determination of plasma NT-proBNP levels allows identification of patients at increased risk of poor outcomes for a more intensive observation and more aggressive pathogenetic therapy.

Topics: Adult; Aged; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Dysfunction, Left; Young Adult

Despite advances in medicine, chronic systolic heart failure (CHF) due to hypertension still constitutes a serious clinical challenge.. The aim of the study was to determine risk mortality factors in a 3-year follow-up of patients with CHF due to hypertension.. The study involved 140 consecutive stable inpatients with CHF (left ventricular end diastolic diameter >57 mm; left ventricular ejection fraction [LVEF] <40%), without epicardial artery stenosis (>30% vessel lumen), significant heart defect, diabetes, neoplastic, disease, or chronic kidney disease, with a minimum 5-year history of hypertension, and administration of angiotensin-converting enzyme inhibitors (or angiotensin II receptor antagonists), β-adrenolytics, spironolactone and furosemide for 3 or more months. The follow-up began on admission to the hospital after laboratory tests, resting electrocardiogram and echocardiogram, six-minute walk test, coronarography, and endomyocardial biopsy. Late follow-up data was obtained from the follow-up visits or by telephone.. The analysis involved 130 of 140 patients aged 47.8 ±7.9 years. The 3-year mortality rate was 18.5%. Independent risk factors for death were LVEF (hazard ratio [HR], 0.881; 95% confidence interval [CI], 0.797-0.975, P <0.05), serum glucose (HR, 1.266; 95% CI, 1.085-1.627; P <0.05), N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.369; 95% CI, 1.166-1.671; P <0.001), and bilirubin levels (HR, 1.057; 95% CI, 1.021-1.094; P <0.01).. Beside LVEF and serum NT-proBNP, other independent risk factors for death in patients with CHF due to hypertension are glucose and bilirubin levels.

Topics: Adult; Aged; Biomarkers; Causality; Chronic Disease; Comorbidity; Confidence Intervals; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Ventricles; Hospitalization; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prognosis; Severity of Illness Index; Survival Analysis; Troponin T

Ivabradin is indicated in patients with compensated chronic heart failure and sinus rhythm with resting heart rate 75 beats per minute despite maximal tolerated beta-blocker dose. Three case reports show favourable effect of ivabradin therapy on heart rate, reverse cardiac remodeling and B-type natriuretic peptide concentration in patients with systolic heart failure.

Topics: Adult; Aged; Benzazepines; Chronic Disease; Cyclic Nucleotide-Gated Cation Channels; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left; Ventricular Remodeling

In article, analysis has been carried out on the influence of recanalization of chronic total occlusion of left anterior descending artery on the course of heart failure in elderly patients who had damage to a single artery and viable myocardium. Recanalization of chronic occlusion of left anterior descending artery together with conservative therapy in elderly patients improves the clinical course of heart failure. A more significant improvement seen in patients with chronic occlusion of left anterior descending artery without history of myocardial infarction.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Coronary Vessels; Exercise Test; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Myocardial Revascularization; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Positron-Emission Tomography; Radiography; Severity of Illness Index; Treatment Outcome

Chronic thromboembolic pulmonary hypertension leads to pulmonary hypertension and right-sided heart failure. The purpose of this study was to investigate the efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension.. Twenty-nine patients with chronic thromboembolic pulmonary hypertension underwent PTPA. One patient had a wiring perforation as a complication of PTPA and died 2 days after the procedure. In the remaining 28 patients, PTPA did not produce immediate hemodynamic improvement at the time of the procedure. However, after follow-up (6.0 ± 6.9 months), New York Heart Association functional classifications and levels of plasma B-type natriuretic peptide significantly improved (both P<0.01). Hemodynamic parameters also significantly improved (mean pulmonary arterial pressure, 45.3 ± 9.8 versus 31.8 ± 10.0 mm Hg; cardiac output, 3.6 ± 1.2 versus 4.6 ± 1.7 L/min, baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51 procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion pulmonary edema as the chief complication. Patients with severe clinical signs and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary edema.. PTPA improved subjective symptoms and objective variables, including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy for the treatment of chronic thromboembolic pulmonary hypertension.. URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.

Topics: Aged; Angioplasty, Balloon; Arterial Pressure; Biomarkers; Chronic Disease; Familial Primary Pulmonary Hypertension; Female; Hospital Mortality; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery; Pulmonary Edema; Pulmonary Embolism; Recovery of Function; Reperfusion Injury; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Topics: Aged; Biomarkers; Chronic Disease; Comparative Effectiveness Research; Early Diagnosis; Echocardiography; Exercise Test; Female; Heart Failure, Diastolic; Humans; Male; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume

We sought to assess the relation of N-terminal brain natriuretic peptide (NT-pro BNP) determined on day 3 after onset of acute myocardial infarction (AMI) symptoms with acute and chronic infarct size and functional parameters assessed by cardiac magnetic resonance (CMR) imaging. Furthermore, we wanted to investigate its predictive value for recovery of myocardial function.. CMR was performed in 49 consecutive patients within 6 days and in a subgroup 4 (n = 27) and 12 (n = 22) months after first acute ST-elevation AMI and successful primary angioplasty. NT-pro BNP was measured in the subacute phase at 66 ± 8 h after onset of symptoms.. Log-transformed NT-pro BNP (lgNT-pro BNP) significantly correlated with infarct size in % of left ventricular myocardial mass (r = 0.59 to 0.64; p < 0.004), with ejection fraction (EF) (r = -0.49 to -0.55; p < 0.004) as well as with segmental wall thickening (SWT, mm) (r = 0.41 to -0.52; p < 0.04) at any time of assessment. Multiple linear regression analysis revealed baseline EF and lgNT-pro BNP to predict global functional recovery. Patients with NT-pro BNP concentrations 1115 pg/ml did not show significant functional recovery (all p = NS).. NT-pro BNP on day 3 after admission correlates with acute and chronic infarct size and myocardial function after AMI. Global and regional myocardial function did not recover in patients with higher NT-pro BNP (>1115 pg/ml) during subacute phase of AMI.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests

Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and WRF.. A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT-pro-BNP with WRF was analysed during a follow up of 18 months.. Twenty-eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063-4765) had significantly higher baseline NT-pro-BNP values than patients without WRF (547 pg/mL, IQR 173-1454). The risk for WRF increased by 4.0 (95% CI 2.1-7.5) for each standard deviation of log NT-pro-BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT-pro-BNP and diabetes were independent predictors of WRF. At a cut-off level of 696 pg/mL, NT-pro-BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF.. NT-pro-BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno-protective strategies in patients with elevated NT-pro-BNP.

Topics: Aged; Biomarkers; Chronic Disease; Disease Progression; Female; Heart Failure, Systolic; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Protein Precursors

Chronic severe pulmonary regurgitation (PR) causes progressive right ventricular (RV) dysfunction and heart failure. Parameters defining the optimal time point for surgery of chronic PR are lacking. The present study prospectively evaluated the impact of preoperative clinical parameters, cardiorespiratory function, QRS duration and NT-proBNP levels on post operative RV function and volumes assessed by cardiac magnetic resonance imaging (CMR) in patients with chronic severe PR undergoing pulmonary valve replacement.. CMR was performed pre- and 6 months postoperatively in 27 patients (23.6 ± 2.9 years, 15 women) with severe PR. Postoperatively, RV endsystolic (RVESVI) and enddiastolic volume indices (RVEDVI) decreased significantly (RVESVI pre 78.2 ± 20.4 ml/m² BSA vs. RVESVI post 52.2 ± 16.8 ml/m²BSA, p<0.001; RVEDVI pre 150.7 ± 27.7 ml/m²BSA vs. RVEDVI post 105.7 ± 26.7 ml/m²BSA; p<0,001). With increasing preoperative QRS-duration, postoperative RVEF decreased significantly (r=-0.57; p<0.005). Preoperative QRS-duration smaller than the median (156 ms) predicted an improved RVEF compared to QRS-duration≥ 156 ms (54.9% vs 46.8%, p<0.05). Multivariate analysis identified preoperative QRS duration as an independent predictor of postoperative RVEF (p<0.005). NT-proBNP levels correlated with changes in RVEDI (r=0.58 p<0,005) and RVESVI (r=0.63; p<0,0001). Multivariate analysis identified NT-proBNP levels prior to PVR as an independent predictor of volume changes (p<0.05).. Valve replacement in severe pulmonary regurgitation causes significant reduction of RV volumes. Both, preoperative NT-proBNP level elevation and QRS prolongation indicate patients with poorer outcome regarding RV function and volumes.

Topics: Adult; Chronic Disease; Electrocardiography; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Prosthesis Implantation; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Preoperative Care; Prospective Studies; Pulmonary Valve; Pulmonary Valve Insufficiency; Time Factors; Ventricular Function, Right; Young Adult

We compared the effect of different loading conditions, parameters of structural heart disease and extracardiac confounders on NT-proBNP to validate the application of NT-proBNP for a characterisation of loading conditions and clinical course of patients with chronic heart diseases.. NT-proBNP was measured in 15 controls and 34 patients with preserved ejection fraction and chronic pressure (by aortic stenosis) or volume overload (by aortic or mitral regurgitation) before and after physical as well as dobutamine stress. Myocardial fibrosis was evaluated by contrast-enhanced cardiovascular magnetic resonance.. In patients with elevated NT-proBNP due to chronic pressure or volume overloaded ventricles, physical and dobutamine stress were associated with only marginal nonsignificant additional NT-proBNP responses. Univariate analyses showed that myocardial fibrosis has the greatest effect on NT-proBNP (P < 0.01). Forward regression analyses revealed left ventricular filling, systolic function, the presence of valvular heart disease, serum creatinine and responses to dobutamine stress as independent determinants of NT-proBNP (P < 0.05 each).. NT-proBNP cannot be used simply to characterise intensity of ventricular load. Character and duration of loading conditions, cardiac structure and function, as well as confounders should be considered when NT-proBNP is used for clinical follow-up assessment.

Topics: Acute Disease; Aged; Biomarkers; Chronic Disease; Dobutamine; Exercise Test; Female; Fibrosis; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Vasodilator Agents; Ventricular Dysfunction, Left

High PTH levels have been reported in patients with chronic heart failure (CHF). Similarly, its levels increase with aging and are related to impaired survival in elderly adults. However, its relationship with neuroendocrine activation and endothelial dysfunction in CHF has not been previously studied. Seventy-three CHF males with New York Heart Association (NYHA) classes II and III and 20 control subjects aged ≥ 55 yr were recruited. PTH, 25-hydroxyvitamin D [25(OH)D], N-terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and osteoprotegerin were measured. Endothelial function (brachial flow mediated dilation), echocardiography, physical performance, and quality of life were assessed, as well. CHF patients had markedly increased serum PTH (77 ± 33 vs 40 ± 11 pg/ml, p<0.0001), NT-pro-BNP [1809 (2742) vs 67 (74) pg/ml, p<0.0001], adiponectin (17 ± 9 vs 10 ± 2 μg/ml, p<0.0001), osteoprotegerin, whereas 25(OH)D levels were decreased compared to controls. Increased PTH is positively correlated with NTpro- BNP (r=0.399, p<0.0001), adiponectin (r=0.398, p<0.0001), and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients. Additionally, increased serum PTH was associated with endothelial dysfunction, echocardiographic variables of heart failure progression, impaired physical performance, and deteriorated quality of life. In a multivariate linear regression analysis, increased serum PTH was independently associated with neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other well-established variables of heart failure severity suggest the potential role of serum PTH in the pathogenesis and non-invasive monitoring of heart failure progression. Future studies are needed to evaluate the predictive value of serum PTH for clinical outcomes as well as beneficial potential of PTH suppression in CHF patients.

Topics: Adiponectin; Aged; Chronic Disease; Endothelium, Vascular; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurosecretory Systems; Osteoprotegerin; Parathyroid Hormone; Peptide Fragments; ROC Curve; Vascular Diseases; Vitamin D

There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy.. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR.. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls.. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomyopathies; Chronic Disease; Disease Models, Animal; Exercise Test; Female; Natriuretic Peptide, Brain; Random Allocation; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Swine; Tachycardia

Increased plasma levels of amino-terminal fraction of brain natriuretic peptide (NT-proBNP) and alterations of diastolic filling as described by Doppler transmitral flow pattern are well-known markers of decompensated heart failure (HF). Recently, some implantable defibrillators have allowed monitoring of intrathoracic impedance, which is related to lung water content, potentially indicating HF deterioration. The aim of this study was to assess the correlation between intrathoracic impedance and NT-proBNP and echo-Doppler transmitral flow indexes.. Data were collected from 111 HF patients, in six Italian centers. All patients were on optimal medical therapy. Device diagnostics, echographic data, NT-proBNP determination, and clinical status as assessed by the Heart Failure Score (HFS) were registered at baseline, at bimonthly visits, and at unscheduled examinations due to HF decompensation or device alerts.. Over a median follow-up of 413 days, 955 examinations were performed. Intrathoracic impedance was significantly correlated with NT-proBNP (P = 0.013) and with mitral E-wave deceleration time (DtE) (P = 0.017), but not with HFS. At the time of confirmed alert events, NT-proBNP was significantly higher than during confirmed nonalert event examinations; DtE did not differ, whereas impedance was significantly lower.. A decrease in intrathoracic impedance is inversely correlated with NT-proBNP and directly correlated with DtE. Intrathoracic impedance monitoring therefore has the physiologic basis for being a useful tool to identify early HF decompensation.

Topics: Aged; Biomarkers; Cardiography, Impedance; Chronic Disease; Coronary Circulation; Electric Impedance; Female; Heart Failure; Humans; Italy; Male; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Stroke Volume

Cardiovascular disease is the major cause of death in hemodialysis (HD) patients. We investigated the relation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left atrial volume index (LAVi) to left ventricular function in chronic HD patients. A total of 117 patients were enrolled as subjects (74 men and 43 women). Echocardiography was performed to evaluate the left atrial volume index (LAVi) and left ventricular mass index (LVMI). Diastolic left ventricular function was estimated as E/E' by tissue Doppler imaging with cardiac ultrasonography. Serum NT-proBNP was measured at the time of echocardiographic measurements. Multiple regression analysis showed that LAVi (F = 24.372, p < 0.0001) and E/E' (F = 23.473, p < 0.0116) were significant predictors for serum NT-proBNP levels, and LVMI (F = 46.807, p < 0.0001) was a best predictor for LAVi among associated factors. These findings suggest that serum NT-proBNP and LAVi are both good biomarkers for predicting the LV remodeling in chronic HD patients.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Heart Atria; Humans; Hypertrophy, Left Ventricular; Japan; Kidney Diseases; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Assessment; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Nurse Practitioners; Respiratory Insufficiency

Soluble ST2 reflects activity of an interleukin-33-dependent cardioprotective signaling axis and is a diagnostic and prognostic marker in acute heart failure. The use of ST2 in chronic heart failure has not been well defined. Our objective was to determine whether plasma ST2 levels predict adverse outcomes in chronic heart failure in the context of current approaches.. We determined the association between ST2 level and risk of death or transplantation in a multicenter, prospective cohort of 1141 chronic heart failure outpatients. Adjusted Cox models, receiver operating characteristic analyses, and risk reclassification metrics were used to assess the value of ST2 in predicting risk beyond currently used factors. After a median of 2.8 years, 267 patients (23%) died or underwent heart transplantation. Patients in the highest ST2 tertile (ST2 >36.3 ng/mL) had a markedly increased risk of adverse outcomes compared with the lowest tertile (ST2 ≤22.3 ng/mL), with an unadjusted hazard ratio of 3.2 (95% confidence interval [CI], 2.2 to 4.7; P<0.0001) that remained significant after multivariable adjustment (adjusted hazard ratio, 1.9; 95% CI, 1.3 to 2.9; P=0.002). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.75 (95% CI, 0.69 to 0.79), which was similar to N-terminal pro-B-type natriuretic peptide (NT-proBNP) (area under the curve, 0.77; 95% CI, 0.72 to 0.81; P=0.24 versus ST2) but lower than the Seattle Heart Failure Model (area under the curve, 0.81 (95% CI, 0.77 to 0.85; P=0.014 versus ST2). Addition of ST2 and NT-proBNP to the Seattle Heart Failure Model reclassified 14.9% of patients into more appropriate risk categories (P=0.017).. ST2 is a potent marker of risk in chronic heart failure and when used in combination with NT-proBNP offers moderate improvement in assessing prognosis beyond clinical risk scores.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Chi-Square Distribution; Chronic Disease; Female; Heart Failure; Heart Transplantation; Humans; Interleukin-1 Receptor-Like 1 Protein; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Receptors, Cell Surface; Risk Assessment; Risk Factors; ROC Curve; Time Factors; United States

There is a close link between heart failure and endothelial dysfunction. Brachial flow-mediated dilation (FMD) is a validated non-invasive measure of endothelial function. The aim of this study was to investigate the clinical correlates of FMD in patients with chronic heart failure (CHF).. We evaluated 60 CHF outpatients (age 62 ± 14 years; 49 males, NYHA class 2.2 ± 0.7, left ventricular ejection fraction, LVEF, 33 ± 8%) taking conventional medical therapy (ACE-inhibitors and/or ARBs 93%, beta-blockers 95%) and in stable clinical conditions.. The maximum recovery value of FMD was calculated as the ratio of the change in diameter (maximum-baseline) over the baseline value.. As compared with patients with a higher FMD, those with FMD below the median value (4.3%) were more frequently affected by ischemic cardiopathy (50 vs. 23%; p = 0.032) and diabetes mellitus (20 vs. 3%; p = 0.044), had a higher NYHA class (2.5 ± 0.5 vs. 1.9 ± 0.7; p < 0.001) and NT-proBNP (2,690 ± 3,690 vs. 822 ± 1,060; p = 0.001), lower glomerular filtration rate estimated by Cockcroft-Gault (GFRCG: 63 ± 28 vs. 78 ± 25; p = 0.001) and LVEF (29 ± 8 vs. 37 ± 9; p = 0.001), as well as more frequently showing a restrictive pattern (40 vs. 7%; p = 0.002). In a multivariate regression model (R (2) = 0.48; p < 0.001), FMD remained associated only with the NYHA class (p = 0.039) and diabetes mellitus (p = 0.024).. This study demonstrates that a better functional status and absence of diabetes mellitus are associated to higher FMD regardless of the etiology of the cardiac disease.

Topics: Aged; Brachial Artery; Chronic Disease; Diabetes Complications; Echocardiography; Endothelium, Vascular; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Regional Blood Flow; Vasodilation; Ventricular Function, Left

Aortic regurgitation (AR) is a chronic disease for which there is currently no approved medical treatment. We previously reported in an animal model that β-blockade with metoprolol exerted beneficial effects on left ventricular remodeling and survival. Despite the recent publication of promising human data, β-blockade in chronic AR remains controversial. More data are needed to support this potentially new treatment strategy. We hypothesized that carvedilol might be another safe treatment option in chronic AR, considering its combined β-blocking and α-blocking effects and proven efficacy in patients with established heart failure.. The effects of a 6-month treatment with carvedilol 30 mg/kg/d orally were evaluated in adult Wistar rats with severe AR. Sham-operated and untreated AR animals were used as controls. Carvedilol treatment resulted in less left ventricular hypertrophy and dilatation. Ejection fraction was improved and filling pressures were reduced by carvedilol. β1-Receptor expression was also improved as well as myocardial capillary density. Those beneficial effects were noted despite the presence of drug-induced bradycardia.. Carvedilol exerted protective effects against volume-overload cardiomyopathy in this model of aortic valve regurgitation with preserved ejection fraction. These results suggest a protective class effect of β-blockers. Combined with the recent publication of promising human data, our findings support the need to carefully design a prospective study in humans to evaluate the effects of β-blockers in chronic aortic valve regurgitation.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Bradycardia; Capillaries; Carbazoles; Carvedilol; Chronic Disease; Disease Models, Animal; Extracellular Matrix Proteins; Follistatin-Related Proteins; Gene Expression Regulation; Heart Rate; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Propanolamines; Rats; Rats, Wistar; Receptors, Adrenergic; RNA, Messenger; Stroke Volume; Time Factors; Ultrasonography; Ventricular Function, Left; Ventricular Pressure

Knowledge of the role of the soluble receptor for advanced glycation end products (sRAGEs) in chronic heart failure (CHF) is very limited. In the present study, we measured plasma sRAGE levels in patients with CHF and examined whether plasma sRAGE predicts prognosis in patients with HF independently of validated scores as the Seattle Heart Failure Score (SHFS). We measured plasma sRAGE in 106 outpatients with CHF. Patients were prospectively followed during a median follow-up period of 1.3 years with end points of cardiac death or rehospitalization. Plasma sRAGE level increased with advancing New York Heart Association functional class, SHFS, age, and ischemic cause. Plasma sRAGE level was also higher in patients with cardiac death and/or events than in event-free patients. In Cox multivariate proportional hazard analysis, SHFS, sRAGE, and N-terminal pro-B-type natriuretic peptide were independent risk factors for cardiac death (sRAGE hazard ratio 1.26, 95% confidence interval 1.09 to 1.45, p = 0.002) and/or cardiac events (sRAGE hazard ratio 1.07, 95% confidence interval 1.03 to 1.11, p = 0.002). Survival curves adjusted by Cox analysis clearly demonstrated that the high-sRAGE group (higher than median) had a significantly higher incidence of cardiac death than the low-sRAGE group (p = 0.001). In conclusion, sRAGE is a novel, highly sensitive, and specific prognostic marker in current optimally treated patients with CHF with an additive and independent value compared to the multimarker SHFS.

Topics: Aged; Analysis of Variance; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Risk Factors; Sensitivity and Specificity; Spain

To analyze usefulness of measurement amino-terminal pro-B type natriuretic peptide of (NT pro-BNP) as the one of parameters of water overload in patients with chronic kidney diseases.. A total number of 277 patients with chronic kidney diseases (CKD) were followed up in the period often years between January 2000 and July 2010. Patients with creatinine clearance of 60 ml/min or less were included in the study. Changes of creatinine clearance, and in last five years changes of NT pro-BNP were followed. Water overload was analyzed using chest x-ray in relation with concentration of NT pro-BNP in the blood.. Decrease of clearance of creatinine ranged from average 54.7 ml/min in the first year to 14.6 ml/min in the fifth year of the monitoring. Average NT pro-BNP level in patients without any sign of water overload was 94 pg/ml (SD 21), mean value in those with Kerley lines was 231 pg/ml/L (SD 64), in those with clear signs of water overload but without pleural effusion it was 525 pg/ml (SD 223), and in those with water retention including pleural effusion it was 1606 pg/ml (SD 1134). Using test of multiple correlation a statistically significant correlation between X-ray signs of water overload and NT pro-BNP concentration was shown, p < 0.05.. Measurement of NT pro-BNP was increased in the beginning of water overload in patients with CKD. Increased value of NT pro-BNP may be found earlier than any other signs of water overload. NT pro-BNP was a useful parameter in estimation of water overload in these patients.

Topics: Biomarkers; Body Water; Chronic Disease; Creatinine; Female; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Uric Acid; Water-Electrolyte Imbalance

We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).. We examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology). Plasma CT-proET-1 was detected using a chemiluminescence immunoassay.. Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04-1.95, p = 0.03) after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF), age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40). Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01) than adding NT-proBNP (p<0.01). Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02).. Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes.

Topics: Aged; Biomarkers; Chronic Disease; Endothelin-1; Female; Heart Failure; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Risk

Neuroendocrine activation with endothelial dysfunction is a key pathophysiological process in chronic heart failure (CHF). Although increased soluble E-selectin (sE-selectin) levels predict adverse events in several forms of cardiovascular disease, there are only scarce data on its predictive value in CHF. The aim of our study was to investigate whether sE-selectin is a useful predictor of mortality in CHF patients and whether its predictive power is additive to that of NT-proBNP.. Plasma levels of sE-selectin were measured by ELISA in 192 CHF patients with clinical systolic heart failure. The study population was followed up for 14.9 months on average; 46 patients died during this period.. Levels of sE-selectin were significantly higher in non-surviving patients than in survivors (p = 0.005) and significantly correlated with the following inflammatory markers: CRP (r = 0.242, p = 0.001), TNF-α (r = 0.201, p = 0.005), TNF-RII (r = 0.207, p = 0.004), and IL-6 (r = 0.339, p < 0.0001). According to Cox regression analysis of the prediction power of sE-selectin for all-cause mortality, high sE-selectin levels independently and significantly predicted short-term mortality in CHF (HR 1.47, 95% CI 1.103-1.956). Furthermore, sE-selectin predicted mortality in CHF patients with concomitant diabetes mellitus, as well as simultaneously elevated sE-selectin and NT-proBNP levels additively predicted mortality.. This study demonstrated a weak correlation of sE-selectin level with inflammatory markers and prediction of short-term mortality in diabetic CHF patients. Elevated serum sE-selectin levels and concomitantly increased NT-proBNP concentrations have additive predictive power in CHF. This suggests that parallel activation of various pathophysiological pathways confers increased risk of adverse outcome in CHF.

Topics: Aged; Chronic Disease; Cohort Studies; Cytokines; Diabetes Complications; E-Selectin; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies

Syndecan-4 is a transmembrane heparan sulfate-carrying glycoprotein that mediates signal transduction pathways activated by growth factors and cell surface receptors, thereby modulating tissue regeneration, angiogenesis, and focal adhesion. The aim of the present study was to determine the clinical use of serum syndecan-4 concentration for diagnosis of heart failure.. Concentration of serum syndecan-4 and other biomarkers of heart failure was measured in 45 patients with heart failure and 21 healthy subjects. Clinical and echocardiographic parameters of cardiac function were recorded.. Serum syndecan-4 concentration significantly increased in proportion to the decrease in ejection fraction (r=-0.599, p<0.001) and increase in the left ventricular (LV) mass index (r=0.315, p<0.05). Serum syndecan-4 concentration was significantly correlated with LV geometrical parameters (i.e. LV mass index, LV end-diastolic volume, and LV dimension), while B-type natriuretic peptide (BNP) was significantly correlated with pressure-related parameters [i.e. early transmitral flow velocity/early diastolic velocity of the mitral valve annulus (E/e'), right ventricular systolic pressure, and left atrial volume index]. Syndecan-4 concentration did not significantly correlate with plasma BNP, transforming growth factor-1, matrix metalloproteinase-2, and tenascin-C concentrations. Serum syndecan-4 concentration could predict cardiac death and re-hospitalization due to heart failure (area under curve, 0.706, p<0.05).. Serum syndecan-4 concentration shows promise as a novel diagnostic and prognostic biomarker for heart failure. Since syndecan-4 correlated with LV geometrical rather than hemodynamic parameters, serum syndecan-4 may represent a biomarker of LV remodeling in the failing heart.

Topics: Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Echocardiography; Female; Heart Failure; Heart Ventricles; Humans; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Stroke Volume; Syndecan-4; Tenascin; Transforming Growth Factors; Ventricular Remodeling

The prognostic value of NT-proBNP levels in patients admitted to hospital due to acute exacerbations of chronic pulmonary diseases (CPDs) is unknown.. Internal Medicine units at two general hospitals.. NT-proBNP levels were obtained within 72 h after admission in 192 consecutive patients with acute exacerbations of CPDs and no history of heart failure or diuretic treatment. Clinical characteristics and main outcomes were assessed over a 12-month follow-up. NT-proBNP cut-points for outcomes were obtained by ROC (receiver operating characteristics) curve analysis.. Chronic obstructive lung disease (69.3%) and chronic asthma (22.4%) were the most prevalent CPDs, and non-pneumonic acute respiratory infection (72.4%) and pneumonia (22.9%) were the most frequent causes of exacerbation. Atrial flutter or fibrillation rate was 11%. During the one-year follow-up period, 22 patients died, 42 were re-admitted, 46 received new long-term oxygen therapy, and 39 received new diuretic treatment. NT-proBNP values correlated with hospitalisation days. NT-proBNP values over 587.9 pg/ml were associated with significantly raised one-year mortality (OR=3.90; 95% IC 1.46-10.47; p=0.006) and over 782.2 pg/ml with cardio-pulmonary deaths (OR=6.38; 95% IC 1.91-21.3; p=0.002). That association persisted after adjustment for age, gender, creatinine levels and cardiac rhythm. NT-proBNP values over 628.7 pg/ml were associated with significantly higher probability of new diuretic treatment (OR=4.38; IC 95% 2.07-9.25; p<0.001). The negative predictive values for these cut-points ranged from 89% to 97%.. NT-proBNP levels below 587.9 pg/ml in patients with acute exacerbations of CPD were associated with favourable one-year outcomes.

Topics: Adult; Aged; Aged, 80 and over; Asthma; Chronic Disease; Female; Follow-Up Studies; Humans; Lung Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pneumonia; Prevalence; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; ROC Curve; Severity of Illness Index

A reciprocal link between inflammation, oxidative/nitrosative stress, and endothelial dysfunction has been postulated in chronic heart failure (CHF). The endothelial repair mechanisms involved remain to be determined. Our aim was to investigate whether there are detectable signs of ongoing angiogenesis in serum of CHF patients and to evaluate the correlation with indexes of haemodynamic and functional impairment.. Enzyme-linked immunosorbent assay tests were used to quantify angiogenin, angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, Tie-2, and brain natriuretic peptide in serum of 87 patients with CHF of increasing severity according to New York Heart Association (NYHA; class I, n = 8; II, n = 45; and III, n = 34) and in 14 healthy subjects matched for age and sex. Angiogenin, angiopoietin-2, and Tie-2 were significantly increased in CHF of increasing severity (Kruskal-Wallis: p = 0.0004, p < 0.0001, and p = 0.017, respectively). Angiopoietin-2 was inversely correlated with the 6-min walking test (r = -0.65, p < 0.0001), peak oxygen consumption (VO(2max); r = -0.57, p = 0.0002), and deceleration time (r = -0.61, p < 0.0001). Multiple regression analysis showed that angiopoietin-2 was mainly associated with VO(2max) (p = 0.018). The angiopoietin-2 area under the receiver operating characteristic curve for CHF diagnosis was 0.94 (95% CI 0.88-0.99; p < 0.001).. These data demonstrate that angiopoietin-2 and selected serum markers of angiogenesis progressively increase with haemodynamic and functional decline in CHF.

Topics: Aged; Analysis of Variance; Angiopoietin-1; Angiopoietin-2; Biomarkers; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Hemodynamics; Humans; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Oxygen Consumption; Peptide Fragments; Receptor, TIE-2; Regression Analysis; Ribonuclease, Pancreatic; Severity of Illness Index; Stroke Volume; Up-Regulation; Vascular Endothelial Growth Factor A; Ventricular Function, Left

Free fatty acids (FFAs) are the major energy sources of the heart, and fatty acids (FAs) are active components of biological membranes. Data indicate that levels of FAs and their composition may influence myocardial function and inflammation. The aim of this study was to investigate whether total levels and composition of FAs and FFAs in plasma are altered in clinical heart failure (HF) and whether any alterations in these parameters are correlated with the severity of HF.. Plasma from 183 patients with stable HF was compared with plasma from 44 healthy control subjects.. Our main findings are as follows: (i) patients with HF had decreased levels of several lipid parameters and increased levels of FFAs in plasma, compared with controls, which were significantly correlated with clinical disease severity. (ii) Patients with HF also had a decreased proportion in the plasma of several n-3 polyunsaturated FAs, an increased proportion of several monounsaturated FAs, and a decreased proportion of some readily oxidized long-chain saturated FAs. (iii) These changes in FA composition were significantly associated with functional class, impaired cardiac function (i.e., decreased cardiac index and increased plasma N-terminal pro-B-type natriuretic peptide levels) and enhanced systemic inflammation (i.e., increased high-sensitivity C-reactive protein levels). (iv) Low levels of C20:4n-3 (eicosatetraenoic acid) and in particular high levels of C18:1n-7 (vaccenic acid) were significantly associated with total mortality in this HF population.. Our data demonstrate that patients with HF are characterized by a certain FA phenotype and may support a link between disturbed FA composition and the progression of HF.

Topics: Adult; Aged; Arachidonic Acids; Biomarkers; C-Reactive Protein; Chronic Disease; Confounding Factors, Epidemiologic; Disease Progression; Fatty Acids, Unsaturated; Female; Heart Failure; Humans; Inflammation; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Oleic Acids; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index

Plasma brain natriuretic peptide (BNP) level increases with symptoms and severity of mitral regurgitation (MR). We aimed to determine the relationship between plasma BNP levels and echocardiographic parameters in patients with acute and chronic MR.. The study included 55 patients (31 males, 24 females) with isolated moderate-to-severe MR. Of these, 31 patients had acute MR, and 24 patients had chronic MR. All the patients were assessed by transthoracic, transesophageal and Doppler echocardiography and plasma BNP levels were determined.. Clinical characteristics and functional capacity were similar in the two groups. Patients with acute MR had significantly higher left ventricular (LV) ejection fraction (EF) (p=0.001), and significantly lower LV end-systolic diameter (p=0.016), end-systolic volume (p=0.027), end-diastolic diameter (p=0.011), left atrial volume (LAV) (p=0.003), and plasma BNP levels (p=0.036). Effective regurgitation orifice area was also significantly higher in patients with acute MR (p=0.038). In multiple linear regression analysis, the natural logarithm of BNP was significantly correlated with E/Ea ratio (β=0.50, p=0.002) and LAV (β=0.38, p=0.015) in patients with acute MR, and with systolic pulmonary artery pressure (β=0.60, p=0.002) and EF (β=-0.36, p=0.039) in patients with chronic MR.. Although the echocardiographic degree of MR was more pronounced in patients with acute MR, serum BNP levels tended to be lower in this group. Correlation of serum BNP with E/Ea and LAV in this group may be an important finding.

Topics: Acute Disease; Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Predictive Value of Tests; Severity of Illness Index

To investigate the correlations between S100B and the severity of cardiac dysfunction, renal insufficiency (RI) and prognosis in chronic heart failure (CHF).. Serum levels of S100B, TNF-α, high sensitivity CRP and NT-proBNP were determined in CHF patients with (n=96) and without RI (n=146). Patients with RI only (n=62) and control subjects (n=64) served for comparison. Patients were followed up for one year.. S100B levels were higher in CHF patients with a further elevation in those with RI (P<0.01). Serum S100B levels correlated with left ventricular ejection fraction, left ventricular end-diastolic volume and NT-proBNP in CHF patients, and eGFR in patients with RI (all P<0.05). Increased S100B levels were associated with major cardiac events (MCE), and were independently associated with the presence of CHF (all P<0.05).. Increased serum S100B levels were associated with the severity of cardiac dysfunction, RI and an adverse prognosis in CHF patients. It represents an independent risk factor for CHF.

Topics: Aged; Body Mass Index; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Growth Factors; Peptide Fragments; Regression Analysis; Renal Insufficiency; ROC Curve; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Tumor Necrosis Factor-alpha

To investigate comorbidities that predict cardiac mortality and re-hospitalization in chronic heart failure (CHF) patients.. Five hundred eighty patients (mean age 63 ± 13 years, 373 male, 207 female, mean ejection fraction (EF) 26 ± 9%) with mild, moderate or severe CHF [NYHA class II-IV] were included in this prospective observational study. We evaluated all comorbidities such as history of ischemic stroke, coronary artery disease, peripheral arterial disease, chronic obstructive lung disease, hypertension, diabetes mellitus and chronic kidney disease in CHF patients who were hospitalized due to decompensated heart failure in Kocaeli University, Faculty of Medicine's Hospital between January 2003 and July 2009. Cox regression and Kaplan-Meier survival analyses were used to establish predictors of unfavorable outcomes.. Of 580 patients 207 (36%) patients died due to cardiovascular reasons. In multivariable Cox regression analysis age (HR-1.06, 95% CI 1.04-1.08, p<0.001), NYHA functional class (HR-3.20 95% CI, 1.90-5.41, p<0.001), history of ischemic stroke (HR-2.48, 95% CI 1.14-5.37, p=0.022), high-sensitive C-reactive protein (HR-1.09, 95% CI, 1.04-1.15, p=0.001), brain natriuretic peptide (HR-1.00, 95% CI 1.00-1.00, p=0.01) and hemoglobin (HR-0.90, 95% CI 0.81-0.99, p=0.038) were independent predictors of cardiac death in the present study. History of ischemic stroke was demonstrated as an important comorbidity that predicts cardiovascular mortality beyond other co-morbidities in CHF patients. NYHA functional class (HR-2.85, 95% CI 1.80-4.65, p<0.001), left ventricular EF [(HR-0.98, 95% CI 0.95-0.99, p=0.039) and ischemic stroke history (HR-2.41, 95% CI 1.15-5.05, p=0.019) were independent predictors for recurrence hospitalization. The stroke history was only predictor showing recurrent hospitalization at least in one year among the other comorbid conditions, which were evaluated during study.. History of ischemic stroke may be an important risk factor for increased cardiac mortality and recurrence hospitalization in CHF patients.

Topics: Aged; Brain Ischemia; Cardiovascular Diseases; Chronic Disease; Comorbidity; Female; Heart Failure; Hemoglobins; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Factors; Stroke; Turkey

We report on a patient suffering from chronic anorexia nervosa who in the course of treatment showed elevated high-sensitive troponin T, creatine kinase and most markedly N-terminal pro-brain natriuretic peptide (NT-proBNP). Elevated enzymes improved significantly throughout the course of treatment without cardiac specific medication but exceeded the normal range for weeks. Abnormally high myocardial enzymes and NT-proBNP in cachectic anorectic patients might resemble conditions of cardiac cachexia. A review of the available literature is provided. Further research is required to explain the pathophysiological meaning of the abnormal laboratory findings.

Topics: Adult; Anorexia Nervosa; Cachexia; Chronic Disease; Creatine Kinase; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

The role of serial NT-proBNP measurements in patients suffering from chronic systolic heart failure (CHF) who already receive individually optimized pharmacotherapy is still unresolved.. NT-proBNP was assessed at baseline and at 6 months follow-up in 504 stable CHF patients treated with individually optimized pharmacotherapy. After assessment of clinical stability at 6 months, patients were followed up for at least 1 year. The combined primary endpoint was defined as death, hospitalization due to cardiac reasons or heart transplantation in 1-year follow-up. We stratified our patients according to two principles: first, a percent change of value (CV) between the first and second measurement of NT-proBNP and secondly, the transformed logarithm of NT-proBNP measured at 6 months.. During the follow-up period of 1 year, 50 patients (9.9%) reached the combined primary endpoint. Stratification according to percentage CV was less accurate in predicting endpoint-free survival compared to a classification in categories of lnNT-proBNP measured at 6 months (ROC AUC = 0.615; 95% CI 0.525-0.70 vs. ROC AUC = 0.790; 95% CI 0.721-0.856, respectively). When entered into proportional hazard regression analysis, lnNT-proBNP measured at 6 months remained an independent predictor of the combined primary endpoint with an associated HR of 2.53 (95% CI 1.385-4.280).. To date, this is the largest analysis of serial NT-proBNP measurements in patients with CHF receiving individually optimized medical therapy. These data suggest that a single NT-proBNP measurement after 6 months in stable clinical conditions may have higher predictive value than stratification of change in serial measurements.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Female; Germany; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing end-stage renal disease (ESRD) in diabetic patients with CKD.. Prospective cohort study nested within a randomized clinical trial.. Patients with type 2 diabetes, CKD (estimated glomerular filtration rate [eGFR], 20-60 mL/min/1.73 m(2)), and anemia enrolled in TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy).. Serum levels of the cardiac biomarkers TnT and NT-pro-BNP.. Incidence of ESRD and the composite of death or ESRD.. We measured TnT and NT-pro-BNP in baseline serum samples from the first 1,000 patients enrolled in TREAT. The relationship of these cardiac biomarker levels to the development of ESRD and death or ESRD was analyzed in multivariable regression models.. Detectable TnT (≥0.01 ng/mL) was present in 45% of participants, and median NT-pro-BNP level was elevated at 605 pg/mL. Higher levels of both cardiac biomarkers were associated independently with higher rates of ESRD, as well as death or ESRD, and remained prognostically important after adjustment for eGFR, proteinuria, and other known predictors of CKD progression. The addition of cardiac biomarkers to a multivariable model for prediction of ESRD improved discrimination of those with and without an event by 16.9% (95% CI, 6.3%-27.4%).. Observational study in a clinical trial cohort; results require validation.. In ambulatory patients with type 2 diabetes, anemia, and CKD, TnT and NT-pro-BNP levels frequently are elevated. These cardiac-derived biomarkers enhance prediction of ESRD beyond established risk factors. Measurement of TnT and NT-pro-BNP may improve the identification of patients with CKD who are likely to require renal replacement therapy, supporting a link between cardiac injury and the development of ESRD.

Topics: Aged; Anemia; Biomarkers; Chronic Disease; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Troponin T

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Chronic Disease; Cost-Benefit Analysis; Defibrillators, Implantable; Echocardiography; Exercise Therapy; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left

The National Institute for Health and Clinical Excellence released its first clinical guideline on heart failure in 2003. This synopsis describes the update of that guideline, which was released in August 2010 and discusses the diagnosis, treatment, and monitoring of heart failure.. Guideline developers considered clinical evidence, health economic analyses, clinical expert opinion, and patient views. Systematic literature searches were performed, and an original decision model assessed the cost-effectiveness of serial measurement of serum natriuretic peptide to monitor patients with chronic heart failure.. First, this guideline update describes the role of serum natriuretic peptide measurement, echocardiography, and specialist assessment in the diagnosis of heart failure. Second, it presents a pathway for pharmacologic treatment, rehabilitation, and pacing therapy (including implantable cardioverter-defibrillator and cardiac resynchronization therapy) for patients with heart failure and left ventricular systolic dysfunction and patients with heart failure and preserved ejection fraction. Finally, it explains the recommendation to monitor patients with heart failure by using serial measurement of serum natriuretic peptide.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Chronic Disease; Cost-Benefit Analysis; Defibrillators, Implantable; Echocardiography; Exercise Therapy; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left

Patients with chronic heart failure are often characterized by impaired renal function, also referred to as cardiorenal syndrome (CRS). The aim of this study was to assess whether novel markers of kidney injury are elevated in chronic heart failure and CRS.. The new renal biomarkers kidney injury molecule-1 (KIM-1), N-acetyl-ß-d-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) were assessed from urine samples of 173 individuals. Patients with chronic heart failure (n= 150) were characterized by decreased ejection fraction (32 ± 9% vs. controls 62 ± 4%, P < 0.001) and increased plasma N-terminal pro-brain natriuretic peptide (median 1460 pg/mL, interquartile range (IQR) 630-3000 pg/mL vs. controls 56, IQR 25-64l pg/mL, P < 0.001). Urinary analysis showed that KIM-1 was significantly elevated in heart failure patients compared with healthy controls (1100, IQR 620-1920 vs. 550, IQR 320-740 ng/g urinary creatinine, P < 0.001). Further, KIM-1 increased significantly with decreasing left ventricular function (r = -0.37, P < 0.001) and severity of New York Heart Association (NYHA)-class (r = 0.5, P < 0.001). N-acetyl-ß-d-glucosaminidase showed a weaker response but correlated significantly with left ventricular dysfunction (r = -0.18, P= 0.015) and more severe clinical condition (r = 0.22, P= 0.04). In contrast, NGAL showed no significant correlation. Kidney injury molecule-1 and NAG were also predictors of all-cause mortality and the composite of all-cause mortality and rehospitalization for heart failure (all P < 0.05).. Kidney injury molecule-1 and NAG are elevated in symptomatic heart failure. This finding may be present in patients with apparently normal kidney function and indicates tubular injury in chronic heart failure. Kidney injury molecule-1 and NAG are potential markers of CRS with additional prognostic value.

Topics: Acetylglucosaminidase; Adult; Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Chronic Disease; Cohort Studies; Disease-Free Survival; Female; Germany; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Male; Membrane Glycoproteins; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Virus; Severity of Illness Index; Syndrome; Urinalysis

Troponin T is an established marker of myocardial ischemia. We speculated that the role of the new high-sensitive troponin T (hs-cTnT) might expand towards non-ischemic myocardial disease, indicate disease severity and allow for prognostication in chronic heart failure.. Hs-cTnT (Roche Diagnostics, Mannheim, Germany) was assessed in 233 individuals with chronic heart failure (n=149) or healthy controls (n=84).. Hs-cTnT was significantly elevated in patients with chronic heart failure [0.018 ng/mL, interquartile range (IQR) 0.009-0.036 ng/mL, vs. controls 0.003 ng/mL, 0.003-0.003 ng/mL, p<0.001] and positively correlated with N-terminal pro-b-type natriuretic peptide (NT-proBNP) (r=0.79, p<0.001). Hs-cTnT increased stepwise and signitificantly according to clinical (NYHA stage) as well as functional (LV ejection fraction, fluid retention) severity (each p<0.001). At a binary cutpoint of 0.014 ng/mL, hs-TropT was a significant predictor of all-cause mortality and all-cause mortality or rehospitalization for congestive heart failure (each p≤0.01). Of note, the prognostic value of hs-TropT was independent and additive to that of NT-proBNP.. Hs-cTnT increases stepwise with the severity of symptoms and LV dysfunction and offers important prognostic information in chronic heart failure, independently from and additive to NT-proBNP. The utility of hs-cTnT expands beyond acute myocardial ischemia and towards chronic heart failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Chronic Disease; Female; Germany; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Troponin T; Ventricular Dysfunction, Left

In order to study special characteristics of chronotropic reaction to physical exercise on veloergometer in the presence of obstructive sleep apnea (OSA) we examined 84 patients with manifestations of chronic systolic heart failure (HF). Chronotropic insufficiency was found in 88% of patients predominantly in combination with insufficient lowering of heart rate after exercise. At the same time it was more rarely registered in patients with OSA (56.4%). Insufficient lowering of heart rate by the end of first minute of rest was similarly associated with HF and OSA.. it is necessary to consider simultaneously chronotropic reserve and character of HR recovery after exercise.

Topics: Aged; Chronic Disease; Echocardiography; Exercise Test; Exercise Tolerance; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Physical Fitness; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive

Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery.. We assessed insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), and measured plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), adiponectin, visfatin, resistin, leptin, and tumor necrosis factor (TNF) α in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (<1 wk) and late (> 6 mo) after clinical recovery, in 26 patients with chronic stable HF, and in 21 patients without HF. NT-proBNP was not increased in control subjects, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to control subjects, plasma adiponectin, visfatin, leptin, resistin, and TNF-α were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin, and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to body mass index in HF patients. HOMA-IR correlated positively with adipokines and TNF-α in HF patients.. ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNF-α, indicative of adipocyte activation. These metabolic abnormalities are reversible, but they temporally lag behind the clinical resolution of decompensated HF.

Topics: Adipokines; Adiponectin; Analysis of Variance; Body Mass Index; Chronic Disease; Disease Progression; Female; Heart Failure; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Resistin; Tumor Necrosis Factor-alpha

The role of N-terminal pro-brain natriuretic peptide (NT-PBP) was analysed in 69 patients with chronic cardiac insufficiency (CCI) of ischemic genesis who developed CCI symptoms after myocardial infarction with the Q-wave on ECG and signed the informed consent. The NT-PBP level was determined in an immunoenzyme assay using Biomedica kits (Slovakia). Statistical treatment of the data was performed with the help of Statistica 7.0 program. The NT-PBP level positively correlated (p < 0.05) with patients' age (r = 0.35) and BMI (r = 0.38), heart rate (r = 0.55), CCI functional class (r = 0.46), CRP level (r = 0.55), left auricle end systolic size (r = 0.53), left ventricle end diastolic size (r = 0.40), left ventricle end diastolic and systolic end volume (r = 0.39 and 0.38), systoloc pressure in the pulmonary artery (r = 0.62), left ventricular myocardial mass (r = 0.58). NT-PBP negatively correlated (p < 0.05) with ejection fraction (r = -0.54). Based on NGT-PBP median, the patients were divided into 2 groups. Group 1 (n = 35) and group 2 (n = 34) comprised patients with NT-PBP levels below and above 120 pmol/ml respectively. Patients of group 2 were significantly older than in group 1 (p = 0.04), had a larger number of previous myocardial infarctions (p = 0.01), more frequent manifestations of CCI (p = 0.04), higher heart rate (p = 0.003) and CRP level (p = 0.005). Patients of group 2 had more frequent adverse events (p = 0.03), increased cholesterol level (p = 0.03), repeated myocardial infarction (p = 0.02), and fatal outcomes (p = 0.01).

Topics: Age Factors; Aged; Biomarkers; Body Mass Index; Chronic Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume

Survival of patients with systolic heart failure (HF) may be influenced by the presence of chronic atrial fibrillation (AF) and circulating concentrations of B-type natriuretic peptides. In this study, we sought to assess the prognostic value of chronic AF in comparison to those of amino-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels and of echocardiographic parameters among HF patients of the entire study population and in those with AF.. Plasma NT-proBNP levels and echocardiography were prospectively assessed in 489 patients with chronic systolic HF (LV ejection fraction

Topics: Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Assessment; ROC Curve; Survival Analysis

To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF).. A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point.. A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p<0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p<0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were independent predictors of the study end point.. In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiac Output; Chronic Disease; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Failure; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; ROC Curve; Severity of Illness Index; Troponin I

Psychological factors, like Type D personality (i.e., the tendency to experience negative emotions and to inhibit emotional distress) have been linked to impaired health outcomes. Criticism on the role of psychological factors in cardiac disease has postulated that such constructs may be confounded by disease severity. Hence, we examined whether Type D personality is associated with brain natriuretic peptide (BNP), a sensitive marker of disease severity in chronic heart failure (CHF), in 202 consecutive CHF outpatients. No differences in logBNP levels were found between Type D and non-Type D patients (t(200) = -1.03, p = .30). After adjusting for demographic and clinical confounders, Type D personality remained unassociated with logBNP levels (β=.04, p = .55), whereas older age (β = .27, p<.001), being prescribed beta-blockers (β = .15, p = .02), lower left ventricular ejection fraction (β = -.38, p<.0001), and kidney dysfunction (β = .17, p = .01) were associated with higher logBNP. To conclude, Type D personality was not associated with BNP in CHF outpatients, whereas clinical variables were associated with BNP. These findings oppose the suggestion that Type D personality is confounded by indicators of disease severity.

Topics: Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Passive-Aggressive Personality Disorder; Severity of Illness Index

High adiponectin concentrations have emerged as an independent risk factor of outcome inpatients with CHF (chronic heart failure); however, modification of adiponectin in CHF patients has not been assessed to date. The aim of the present study was to investigate the effect of exercise training on adiponectin levels in CHF patients. A total of 80 patients with CHF due to systolic dysfunction were included. The effect of 4 months exercise training was studied in 46 patients,whereas the remaining 34 untrained CHF patients served as a sedentary control group. Circulating adiponectin concentrations, exercise capacity, anthropometric data and NT-proBNP (N-terminal pro-brain natriuretic peptide) levels were assessed. Adiponectin levels were significantly higher in CHF patients compared with healthy subjects [9.3 (7.1-16.1) and 4.9 (3.9-8.6) mg/l respectively;P=0.015]. Stratification of CHF patients according to tertiles of NT-proBNP revealed an increase in adiponectin with disease severity (P<0.0001). Exercise training reduced circulating adiponectin levels in CHF patients [10.7 (7.2-17.6) mg/l before training to 9.4 (5.9-14.8) mg/l after training;P=0.013], whereas no changes were observed in the sedentary CHF group [9.0 (7.0-13.5) mg/l before training and 10.1 (6.0-15.7) mg/l after a similar time interval]. A significant time x group interaction (P=0.008) was observed for the mean change in adiponectin between the trained and untrained CHF patients. Adiponectin concentrations were positively associated with NT-proBNP and HDL (high-density lipoprotein)-cholesterol and negatively correlated with BMI (body mass index), triacylglycerols and exercise capacity. In conclusion, circulating adiponectin concentrations are higher in CHF patients compared with healthy subjects and increase with disease severity.Exercise training for 4 months lowers circulating adiponectin levels.

Topics: Adiponectin; Case-Control Studies; Chronic Disease; Exercise; Exercise Tolerance; Female; Heart Failure, Systolic; Humans; Lipoproteins, HDL; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Regression Analysis

Serial measurements of neurohormones have been shown to improve prognostication in the setting of acute heart failure (HF) or chronic HF without therapeutic intervention. We investigated the prognostic role of serial measurements of emerging neurohormones and BNP in a cohort of chronic HF patients undergoing increases in HF-specific therapy.. In this prospective study we included 181 patients with chronic systolic HF after an episode of hospitalization for worsening HF. Subsequently, HF therapy was gradually increased in the outpatient setting until optimized. We measured copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide before and after optimization of HF therapy. The primary endpoint was all-cause mortality at 24 months.. Angiotensin-converting enzyme/angiotensin receptor blocker and beta-blockers were increased significantly during the 3-month titration period (P < 0.0001 for both). In a stepwise Cox regression analysis adjusted for age, sex, glomerular filtration rate, diabetes mellitus, and ischemic HF, baseline and follow-up neurohormone concentrations were predictors of the primary endpoint as follows (baseline hazard ratios): copeptin 1.92, 95% CI 1.233-3.007, P = 0.004; midregional proadrenomedullin 2.79, 95% CI 1.297-5.995, P = 0.009; midregional proatrial natriuretic peptide 2.05, 95% CI 1.136-3.686, P = 0.017; C-terminal endothelin-1 precursor fragment 2.24, 95% CI 1.133-4.425, P = 0.025; B-type natriuretic peptide 1.46, 95% CI 1.039-2.050, P = 0.029.. In pharmacologically unstable chronic HF patients, baseline values and follow-up measures of copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide were equally predictive of all-cause mortality. Relative change of neurohormone values was noncontributory.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Endothelin-1; Female; Glycopeptides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Prognosis; Protein Precursors

Congestive heart failure (CHF) has been associated with elevated biomarker levels reflecting chronic low-grade inflammation. YKL-40 is a biomarker with increasing levels in patients with cardiovascular disease (CVD) of increasing severity. Furthermore, YKL-40 is associated with all-cause and cardiovascular mortality. We investigated plasma YKL-40 levels in patients with CHF and evaluated the possible predictive value with respect to overall mortality and recurrent cardiovascular outcomes.. Plasma YKL-40 was measured in 194 CHF patients and in 117 age-matched individuals without CVD.. Median YKL-40 levels were approximately 77% higher in patients with CHF (106 (IQR, 66-184) ng/ml vs. 60 (IQR, 42-97) ng/ml, p < 0.0001). We found a trend towards an association of YKL-40 levels with urinary albumin/creatinine ratio (UACR) (beta = 0.12, p = 0.08). YKL-40 levels were not predictive of overall mortality (p = 0.59), major cardiovascular events (p = 0.23) or events of incompensation (p = 0.56).. Plasma YKL-40 levels are elevated in patients with CHF but show no association with other clinical or paraclinical variables. YKL-40 levels were not predictive of overall mortality or incident cardiovascular events. Most likely, elevated YKL-40 levels in CHF patients are explained by the presence of concomitant diseases but a role of YKL-40 in low-grade inflammation is not excluded.

Topics: Adipokines; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Case-Control Studies; Chitinase-3-Like Protein 1; Chronic Disease; Comorbidity; Creatinine; Denmark; E-Selectin; Female; Glycoproteins; Heart Failure; Humans; Lectins; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Up-Regulation; von Willebrand Factor

Cardiac disease is a significant complication of childhood oncologic therapy. We report the case of a 14-year-old female with acute promyelocytic leukemia who developed symptomatic cardiomyopathy only 4 months into treatment with a combination of daunomycin and all-trans retinoic acid (ATRA). Despite cessation of daunomycin, she demonstrated fluctuating systolic function in relation to ATRA administration. Improvement and deterioration in systolic function on echocardiogram and serum B-natriuretic peptide levels were seen while receiving ATRA 1 week on and 1 week off, respectively, during the maintenance phase of therapy.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Chronic Disease; Daunorubicin; Female; Humans; Leukemia, Promyelocytic, Acute; Natriuretic Peptide, Brain; Tretinoin

Plasma B-type natriuretic peptide (BNP) levels are confounded by renal dysfunction, so this study examined whether plasma BNP might be a reliable biomarker of the onset of cardiovascular (CV) events in a population-based cohort with impaired renal function.. Baseline data, including plasma BNP, serum creatinine, and urinary protein levels, were determined in participants from a community-based population. Estimated glomerular filtration rate (eGFR) was calculated, and chronic kidney disease (CKD) was defined as either: eGFR <60 mlxmin(-1)x1.73 m(-2) and/or proteinuria (CKD definition-1) or GFR <60 mlxmin(-1)x1.73 m(-2) (CKD definition-2). The CV endpoint was surveyed prospectively. The cohorts were followed for 5,275 person-years for CKD definition-1, and for 4,350 person-years for CKD definition-2. The CV event-free survival rate in the highest BNP quartile in either CKD definition was the lowest among the quartile groups (P<0.001). In multivariate Cox regression models adjusted by traditional CV risk factors and atrial fibrillation, relative risk (RR) for CV events was significantly higher in the highest BNP quartile compared with the lowest BNP quartile (CKD definition-1, RR 3.51, P<0.01: CKD definition-2, RR 4.67, both P<0.01).. Plasma BNP level provides strong predictive information about the future onset of CV events in CKD subjects selected from the general population.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Creatinine; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors

The incidence of congestive heart failure is 3-fold greater than that of acute coronary syndrome in haemodialysis (HD) patients. The purpose of this study was to determine if blood flow through an arteriovenous (AV) access contributes to an increase in left ventricular mass (LVM) that may increase the risk of congestive heart failure.. We conducted a 1-year prospective cohort study at two Canadian centres of HD patients at high risk for congestive heart failure who had a first AV access created. Patients underwent echocardiography and measurement of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels before and 1-year post-AV access creation. Access flows were measured within the first month of access maturation and 1-year post-access creation. Data were analysed using descriptive statistics, Student's t-test, correlation coefficients and regression.. One-year post-AV access creation, LVM increased by 12.2 +/- 32% (P = 0.025) and plasma NT-proBNP levels increased by 170 +/- 465% (P = 0.02). The average AV access blood flow did not correlate with an increase in LVM or NT-proBNP levels.. In patients on chronic HD after 1 year, AV access flow does not correlate with increases in LVM by echocardiography or plasma levels of NT-proBNP.

Topics: Aged; Arteriovenous Shunt, Surgical; Canada; Chronic Disease; Cohort Studies; Echocardiography; Female; Heart Failure; Heart Ventricles; Humans; Kidney Diseases; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Regional Blood Flow; Renal Dialysis; Retrospective Studies; Risk Factors; Ventricular Remodeling

Vitamin D deficiency is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effects of oral cholecalciferol supplementation on mineral metabolism, inflammation, and cardiac dimension parameters in long-term hemodialysis (HD) patients.. This 1-year prospective study included 158 HD patients. Serum levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, and plasma brain natriuretic peptide as well as circulating bone metabolism and inflammation parameters were measured before and after supplementation. Baseline 25(OH)D and 1,25(OH)(2)D levels were measured twice (end of winter and of summer, respectively). Therapy with paricalcitol, sevelamer, and darbepoietin was evaluated.. There was an increase in serum 25(OH)D and 1,25(OH)(2)D levels after supplementation. Conversely, serum calcium, phosphorus, and intact parathyroid hormone were decreased. There was a reduction in the dosage and in the number of patients who were treated with paricalcitol and sevelamer. Darbepoietin use was also reduced, with no modification of hemoglobin values. Serum albumin increased and C-reactive protein decreased during the study. Brain natriuretic peptide levels and left ventricular mass index were significantly reduced at the end of the supplementation.. Oral cholecalciferol supplementation in HD patients seems to be an easy and cost-effective therapeutic measure. It allows reduction of vitamin D deficiency, better control of mineral metabolism with less use of active vitamin D, attenuation of inflammation, reduced dosing of erythropoiesis-stimulating agents, and possibly improvement of cardiac dysfunction.

Topics: Administration, Oral; Aged; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; C-Reactive Protein; Calcitriol; Calcium; Chelating Agents; Cholecalciferol; Chronic Disease; Darbepoetin alfa; Dietary Supplements; Ergocalciferols; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Parathyroid Hormone; Phosphorus; Polyamines; Prospective Studies; Renal Dialysis; Serum Albumin; Sevelamer; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

We, in the present study, studied the stability, operability, and economy as a whole of NT-proBNP assay, and further on the performance of diagnosing cardiac failure as a laboratory test. It was found to be superior to BNP assay not only as a reagent but also as a clinical test to diagnose cardiac functions. On the other hand, it is reported that NT-proBNP is influenced by the renal function more than BNP, and we investigated it precisely. As a result, NT-proBNP was equally influenced as BNP when the estimated glomerular filtration rate (eGFR) was more than 60 ml/min. When eGFR decreased further, BNP was also increased by the decreased renal clearance. Thereby, NT-proBNP was increased relatively more than BNP because BNP was catabolized by other mechanisms than renal clearance. Therefore, NT-proBNP may be superior to BNP in regard to estimate secretion of BNP from the heart particularly when renal function was decreased. In conclusion, NT-proBNP is an excellent biomarker to diagnose heart failure.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Heart Function Tests; Humans; Immunoassay; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Young Adult

Topics: Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Longitudinal myocardial deformation indexes appear superior to left ventricular ejection fraction (LVEF) in assessing myocardial contractility. However, few studies have addressed the prognostic value of longitudinal motion markers (velocity, strain, and strain rate) in predicting outcome in heart failure patients.. The study included 125 consecutive symptomatic heart failure patients (63+/-16 years, 77% male, LVEF=31+/-10%). All patients underwent a complete echocardiographic and clinical examination, and brain natriuretic peptide level was assessed in 93 patients. Longitudinal myocardial velocity by tissue Doppler imaging, global-epsilon, and strain rate by speckle tracking were computed from apical views (4-, 3-, and 2-chambers views) and compared with the occurrence of major adverse cardiac events. On the whole, peak longitudinal velocity, global-epsilon, and strain rate averaged 5+/-2 cm/s (range, 1 to 9), -8+/-3% (range, -3 to -18), and -0.33+/-0.16 s(-1) (range, -0.83 to -0.05), respectively. During the follow-up period (266+/-177 days), major adverse cardiac events occurred in 47 (38%) patients (15 deaths, 29 recurrent heart failure, and 4 heart transplantations). By univariable analysis using Cox model global-epsilon, strain rate, and LVEF were associated with the occurrence of major adverse cardiac events, whereas only global-epsilon remained independently predictive of outcome by multivariate analysis.. In the heart failure population, longitudinal global strain by speckle tracking is superior to LVEF and other longitudinal markers in identifying patients with poor outcome.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure; Heart Function Tests; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Observer Variation; Predictive Value of Tests; Prognosis; Reproducibility of Results; Ventricular Dysfunction, Right; Young Adult

Topics: Biomarkers; Cardiovascular Diseases; Chronic Disease; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Risk Factors

It was to establish whether brain natriuretic peptide (BNP) might predict cardiac dysfunction in children with chronic kidney disease (CKD).. The relation between BNP, echocardiography and risk factors (hypertension, anemia, lipids, CRP, hyperparathyroidism) was investigated in 46 children (10 pre-dialysis patients, 14 on dialysis, 11 children with kidney transplants, and 11 healthy controls). Data on BNP were transformed into common logarithms (log(10) BNP, log BNP).. log BNP was significantly higher in dialysis patients when compared to controls (2.09 +/- 0.78 vs. 1.43 +/- 0.34 pg/ml, p = 0.012) and patients in the pre-dialysis stage (2.09 +/- 0.78 vs. 1.52 +/- 0.42 pg/ml, p = 0.039). log BNP in transplanted children was not significantly different from healthy children (2.09 +/- 0.78 vs. 1.71 +/- 0.46 pg/ml, p = 0.19). Abnormal heart geometry (concentric and eccentric hypertrophy, concentric remodeling) was found in 19 patients (54.28%). A significant correlation was observed between log BNP and ventricular hypertrophy (r = 0.515, p = 0.001). Compared to controls higher log BNP was seen in children with eccentric hypertrophy than in children with concentric hypertrophy (2.178 +/- 0.956 vs. 1.496 +/- 0.395 pg/ml, p = 0.05, or 1.982 +/- 0.618 vs. 1.496 +/- 0.395, p = 0.04).. BNP might predict an abnormal geometry in children with CKD.

Topics: Adolescent; Biomarkers; Cardiomegaly; Cardiovascular Diseases; Case-Control Studies; Child; Chronic Disease; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Young Adult

Measurement of natriuretic peptide's (NP) release in response to hemodynamic stress may be complementary to its baseline assessment in individuals. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) increase in patients with atrial fibrillation (AF) and decrease after successful cardioversion, suggesting that AF may stimulate secretion of NPs. However, there are conflicting data on the predictive value of NPs on the cardioversion outcome.. The purpose of this study was to investigate whether baseline and exercise-induced NP plasma levels can be useful in predicting successful cardioversion of persistent AF and maintenance of sinus rhythm during 6-month follow-up.. A prospective study enrolled 77 consecutive subjects with persistent AF with normal left ventricular function, referred for elective cardioversion. Patients underwent a modified Bruce protocol treadmill exercise test 24 hours before cardioversion. Blood samples for ANP and BNP analyses were obtained at rest and 5 minutes after exercise peak.. The group of successful cardioversion and stable sinus rhythm presented higher exercise ANP (110.6 ± 41.2 pg/mL vs 43.8 ± 36.1; pg/mL, P < 0.0001) and lower BNP increase (5.2 ± 5.2 pg/mL vs 40.5 ± 34.2 pg/mL, P < 0.0001) than the group of unsuccessful cardioversion or AF recurrence. Using an optimized cutoff level of ≤12% of relative exercise-induced increase in BNP concentration, and of >50 pg/mL of ANP increase, successful cardioversion can be predicted with high accuracy.. An increase in ANP and stability of BNP plasma concentration during exercise testing are independently associated with successful cardioversion and maintenance of sinus rhythm during 6-month follow-up. (PACE 2010; 33:1203-1209).

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Coronary Sinus; Electric Countershock; Exercise Test; Humans; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Treatment Outcome

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cohort Studies; Diuretics; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Survival Analysis; Treatment Outcome

Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF.. In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 microg/L, or 100-300 microg/L with transferrin saturation <20%. The prevalence of ID was 37 +/- 4% [+/-95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P < 0.01).. In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.

Topics: Aged; C-Reactive Protein; Chronic Disease; Disease-Free Survival; Female; Ferritins; Heart Failure, Systolic; Humans; Iron Deficiencies; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Transferrin

To explore the covariate-adjusted associations between body composition (percent body fat and lean body mass) and prognostic factors for mortality in patients with chronic heart failure (CHF) (nutritional status, N-terminal pro-B-type natriuretic peptide [NT-proBNP], quality of life, exercise capacity, and C-reactive protein).. Between June 2008 and July 2009, we directly measured body composition using dual energy x-ray absorptiometry in 140 patients with systolic and/or diastolic heart failure. We compared body composition and CHF prognostic factors across body fat reference ranges and body mass index (BMI) categories. Multiple linear regression models were created to examine the independent associations between body composition and CHF prognostic factors; we contrasted these with models that used BMI.. Use of BMI misclassified body fat status in 51 patients (41%). Body mass index was correlated with both lean body mass (r=0.72) and percent body fat (r=0.67). Lean body mass significantly increased with increasing BMI but not with percent body fat. Body mass index was significantly associated with lower NT-proBNP and lower exercise capacity. In contrast, higher percent body fat was associated with a higher serum prealbumin level, lower exercise capacity, and increased C-reactive protein level; lean body mass was inversely associated with NT-proBNP and positively associated with hand-grip strength.. When BMI is divided into fat and lean mass components, a higher lean body mass and/or lower fat mass is independently associated with factors that are prognostically advantageous in CHF. Body mass index may not be a good indicator of adiposity and may in fact be a better surrogate for lean body mass in this population.

Topics: Absorptiometry, Photon; Adult; Alberta; Analysis of Variance; Bias; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Chronic Disease; Cross-Sectional Studies; Exercise Tolerance; Female; Hand Strength; Heart Failure; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nutritional Status; Obesity; Peptide Fragments; Prealbumin; Predictive Value of Tests; Prognosis; Quality of Life; Risk Factors

Topics: Biomarkers; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Survival Rate

Persistent atrial fibrillation (AF) leads to electrical, structural and neurohormonal remodelling of the atria, including increased plasma B-type natriuretic peptide (BNP) level.. To assess the clinical value of plasma BNP or NT-proBNP concentrations in patients with persistent AF measured before and after sinus rhythm restoration following direct-current cardioversion.. The study group consisted of 43 patients with persistent AF who underwent successful electrical cardioversion. The mean AF duration was 12.3 weeks. Patients in the study group had no symptoms of heart failure and they had preserved left ventricular systolic function. Blood samples were collected twice: 24 hours before and 24 hours after electrical cardioversion. Logistic regression analysis was used to assess the predictive value of BNP and NT-proBNP levels.. Baseline NT-proBNP and BNP levels were increased in patients with persistent AF (290.9 +/- 257.2 pg/mL and 148.4 +/- 111.4 pg/mL, respectively) compared to a matched control group without AF (47.8 +/- 80.6 pg/mL; p = 0.0001 and 74.9 +/- 81.7 pg/mL; p = 0.01). Plasma BNP level decreased 24 hours after cardioversion (from 148.4 +/- 111.4 to 106.4 +/- 74.7 pg/mL; p = 0.0045) whereas NT-proBNP level did not (from 290.9 +/- 257.2 to 262.7 +/- 185.6 pg/mL; NS). During an 18-month follow-up period, 21 (49%) patients remained in sinus rhythm. Neither baseline plasma BNP nor NT-proBNP level predicted sinus rhythm maintenance.. NT-proBNP and BNP plasma levels are increased in patients with persistent AF. Conversion to sinus rhythm is associated with a significant decrease in plasma BNP but not NT-proBNP level. Baseline BNP and NT-proBNP levels do not predict long-term sinus rhythm maintenance.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Diabetes Complications; Echocardiography; Electric Countershock; Female; Follow-Up Studies; Humans; Hypertension; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Young Adult

Topics: Atrial Fibrillation; Biomarkers; Chronic Disease; Electric Countershock; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Prognosis; Protein Precursors

Corin is a serine protease that cleaves pro-atrial and pro-B-type natriuretic peptides into biologically active hormones. The relationship between soluble plasma corin levels, plasma natriuretic peptide levels, myocardial structure and performance, and long-term clinical outcomes in the setting of chronic systolic heart failure has not been described.. In 126 patients with chronic systolic heart failure (left ventricular ejection fraction

Topics: Adult; Aged; Biomarkers; Cardiomegaly; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis; Prospective Studies; Serine Endopeptidases

The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Chi-Square Distribution; Chronic Disease; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Humans; Japan; Kaplan-Meier Estimate; Kidney; Kidney Diseases; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha.. To test the hypothesis of the possible beneficial impact of IL-10 on mortality in systolic heart failure patients in relation to their circulating TNFalpha levels.. We measured circulating levels of IL-10 and TNFalpha in 67 ambulatory systolic heart failure patients (age 65 +/- 13 years).. Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFalpha (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR 3.67, 95% confidence interval 1.14-11.78).. Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFalpha had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.

Topics: Aged; Body Mass Index; C-Reactive Protein; Cause of Death; Cholesterol; Chronic Disease; Creatinine; Echocardiography; Electrocardiography; Exercise Test; Female; Follow-Up Studies; Heart Failure, Systolic; Hemoglobins; Humans; Interleukin-10; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume; Troponin T; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Cardiopulmonary exercise testing is a well-established tool for clinical and prognostic assessment of patients with chronic heart failure (CHF). Recently, a new parameter of this examination--oxygen uptake efficiency slope (OUES)--has been described and proposed as a new prognostic factor in patients with CHF. Brain natriuretic peptide (BNP) is an established prognostic factor in CHF. The purpose of the study was to assess OUES in patients with CHF in relation to other cardiopulmonary parameters and BNP levels.. The study group consisted of 42 patients with CHF and left ventricular ejection fraction (LVEF) < 45% (mean age 50.2 +/- 9.3 years, mean ejection fraction 26.1 +/- 8.1% and NYHA functional class - 2.5 +/- 0.8) and eight healthy controls (age 43.6 +/- 14.7 years). Coronary artery disease was diagnosed in 16 patients (38%). All underwent maximal cardiopulmonary exercise treadmill test. BNP level was measured using Abbott AxSYM Immunoassay system.. There were significant (p < 0.001) differences between the patients and controls in BNP levels (350 +/- 520 vs 14 +/- 19 pg/mL), OUES (1.7 +/- 0.4 vs 2.7 +/- 0.5), peak VO(2) (17.1 +/- +/- 5.1 vs 36.9 +/- 4.9 mL/kg/min), O(2) pulse (10.9 +/- 3.3 vs 15.9 +/- 2.7) and VE/VCO(2) slope (35.7 +/- 7.8 vs 25.7 +/- 2.7). In patients, OUES was significantly (p < 0.001) correlated with LVEF (r = 0.54), BNP levels (r = -0.49), peak VO(2) (r = 0.80), VO(2) AT (r = 0.65) and VE/VCO(2) slope (r = -0.59). BNP was independently related to OUES in multivariate regression analysis.. Oxygen uptake efficiency slope is significantly reduced in patients with CHF and correlates with peak VO(2) and other parameters of cardiopulmonary exercise treadmill test. It is not related to age. BNP is an independent marker of OUES in patients with CHF.

Topics: Adult; Biomarkers; Case-Control Studies; Chi-Square Distribution; Chronic Disease; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Oxygen; Oxygen Consumption; Poland; Predictive Value of Tests; Prognosis; Pulmonary Ventilation; Regression Analysis; Stroke Volume; Ventricular Function, Left

Immune activation and inflammation participate in the progression of chronic heart failure (CHF), and T helper (Th) lymphocytes play critical roles in it. Th17 cells and CD4(+)CD25(+) regulatory T (Treg) cells both come from naive Th cells, share reciprocal development pathways but exhibit opposite effects, and the balance between them controls inflammation and autoimmune diseases. We hypothesized that the Th17/Treg balance was impaired in patients with CHF.. To assess our hypothesis, patients with CHF were divided into 2 groups: heart failure with normal ejection fraction (HFNEF) group and heart failure with reduced ejection fraction (HFREF) group. Peripheral Th17 and Treg frequencies were analyzed by flow cytometry.. Patients with HFNEF and HFREF both revealed significant increase in the frequencies of Th17 and obvious decrease in the frequencies of Treg compared with the controls.. The results indicate that the Th17/Treg imbalance exists in patients with CHF, suggesting the imbalance potentially plays a role in the pathogenesis, and the Th17/Treg balance may be a promising therapeutic approach in patients with CHF.

Topics: Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; T-Lymphocytes, Regulatory; Th17 Cells

The objective of this study was to investigate functional effects of immunoadsorption (IA) in patients with chronic nonfamilial dilated cardiomyopathy (DCM) regarding clinical and humoral markers of heart failure.. IA has been shown to induce early hemodynamic improvement in patients with nonfamilial dilated cardiomyopathy (DCM).. We performed IA using protein A agarose columns on five consecutive days in 51 patients with chronic DCM, congestive heart failure of NYHA class ≥ II, left ventricular ejection fraction ≤50%, and mean time since initial diagnosis of 5.0 ± 5.8 years.. Immediately after IA, immunoglobulin G (IgG) decreased by 89.4% and IgG3 by 66.7% (both P < 0.0001). Median NT-pro BNP was reduced from 1230.0 ng L(-1) at baseline to 829.0 ng L(-1) after 6 months (P < 0.0001). Also mean left ventricular ejection fraction (LVEF) was significantly improved (26.3% ± 9.4% to 28.7% ± 11.4% after 6 months, P = 0.016) and LVEF improved ≥5% (absolute) in 21 of 51 (41.2%) patients. After 6 months, bicycle spiroergometry showed a significant increase in exercise capacity from 82.0 ± 30.8 Watts to 93.1 ± 34.3 Watts (P = 0.008) while VO2max rose from 15.0 ± 4.1 to 16.4 ± 4.8 mL min(-1) kg(-1) (P = 0.01).. In this study, on heart failure patients with nonfamilial DCM, IA therapy significantly improved clinical and humoral markers of heart failure severity. These promising results may be due to the selected study population, with a shorter disease duration and the higher amount of IgG 3 reduction. Future blinded prospective multicenter studies are necessary to identify those patients that benefit most.

Topics: Adult; Aged; C-Reactive Protein; Cardiomyopathy, Dilated; Chronic Disease; Exercise; Female; Humans; Immunoglobulin G; Immunosorbent Techniques; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Staphylococcal Protein A

To investigate the effect of metoprolol succinate sustained-release tablets on cardiac function, serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) in elderly hypertensive patients and its relation with pulse pressure (PP).. A total of 330 elderly hypertensive patients with chronic heart failure receiving basic therapy were included. Before initiation and 3 months after the maximal tolerated dose of metoprolol succinate sustained-release tablets, the parameters of blood pressure, clinical features, radionuclide ventriculographic and laboratory findings of the patients were analyzed.. As the PP was elevated, the serum levels of VEGF, hs-CRP and BNP increased and the cardiac systolic and diastolic functions decreased. In patients with PP of 59-68 mmHg and > 68 mmHg, 3 months of treatment with the tablets caused significantly increased LVEF by (3.32 ± 2.35)% and (4.12 ± 3.05)% and LVPER by 0.37 ± 0.26 and 0.53 ± 0.37, respectively; PP were decreased by 8.2 ± 3.1 mmHg and 9.4 ± 4.3 mmHg and VEGF by 18.39 ± 8.43 pg/ml and 26.79 ± 14.32 pg/ml, respectively. The treatment also resulted in lowered hs-CRP and BNP in these patients by 0.26 ± 0.13 mg/L and 0.33 ± 0.16 mg/L and by 140.36 ± 68.62 ng/L and 155.39 ± 73.58 ng/L, respectively.. Obvious elevation of PP is associated with a better response to metoprolol succinate sustained-release tablets in elderly hypertensive patients with chronic heart failure, and 3 months of treatment with the tablets can significantly improve the cardiac function and lower the levels of VEGF, hs-CRP and BNP in these patients.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Blood Pressure; C-Reactive Protein; Chronic Disease; Delayed-Action Preparations; Female; Heart Failure; Humans; Hypertension; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Vascular Endothelial Growth Factor A

Topics: Adult; Biomarkers; Chronic Disease; Diagnostic Imaging; Health Services Accessibility; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic

The aim of this study was to investigate preoperative clinical and echocardiographic characteristics and N-terminal pro-B type natriuretic peptide (NT-proBNP) levels as prognostic factors for regression of the left ventricular (LV) mass after valvular surgery in patients with chronic severe mitral regurgitation (MR).. One hundred seventeen patients undergoing surgery for chronic severe MR were included. Plasma NT-proBNP measurements and echocardiography were performed preoperatively, immediately postoperatively, and at six and 12 months after surgery. Any regression of the LV mass was evaluated by echocardiography.. During follow-up, 90 patients (77%) were classified as an LV mass regression group (LVMR), defined as having a postoperative reduction in LV mass indexed against body surface area (LVMI). The remaining 27 (23%) patients were classified as NON-LVMR. The LVMR group was younger (p=0.029) and had significantly lower ratios of patients with hypertension (p=0.045) and diuretic use (p=0.005) than the NON-LVMR group. They also had lower levels of NT-proBNP (median: 446.4 pg/ml versus 1394.0 pg/ml, p=0.001). In multivariate analysis, higher preoperative NT-proBNP levels were independent predictors of no significant regression of the LV mass (odds ratio=1.731, 95% confidence intervals 1.052-2.844, p=0.010).. A lower preoperative NT-proBNP level predicted the regression of LV mass after valvular surgery in patients with chronic severe MR. This measure could be used as a biomarker for predicting the postoperative course in such patients.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Preoperative Care; Retrospective Studies; Severity of Illness Index; Ventricular Dysfunction, Left

Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients.A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event.During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were < 2.12 pg/mL for free triiodothyronine and > 686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine < 2.12 pg/mL and among patients with brain natriuretic peptide > 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide.In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure.

Topics: Aged; Biomarkers; Cardiomyopathy, Dilated; Chi-Square Distribution; Chronic Disease; Down-Regulation; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Time Factors; Triiodothyronine; Turkey; Up-Regulation

This article describes the diagnostic possibilities of research of NT-BNP level in blood of the patients of elderly and senile age with congestive heart failure. Statistically significant correlation between BNP concentration and a functional class of heart insufficiency is revealed. Definition of BNP level enables to diagnose differentially the difficult forms of congestive heart failure.

Topics: Aged; Aged, 80 and over; Aging; Biomarkers; Cardiac Output; Chronic Disease; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Severity of Illness Index

In the elderly the diagnosis of chronic heart failure is often challenging and the availability of echocardiography can be limited. Plasma levels of NT-proBNP are valuable tools to diagnose patients with heart failure. However, the performance of this biomarker to detect cardiac abnormalities in the very elderly remains unclear. The aims of this study were to investigate the relation between NT-proBNP and cardiac abnormalities and to evaluate the use of NT-proBNP to exclude structural and functional cardiac abnormalities in a community-based sample of "well-functioning" nonagenarians.. A diagnostic cross-sectional study embedded within the Leiden 85-plus Study in the municipality of Leiden, the Netherlands. Plasma NT-proBNP levels were measured and 2-dimensional echocardiography was performed in a subgroup of 80 well-functioning nonagenarians. Linear regression analysis was used to explore the relation between NT-proBNP and cardiac abnormalities and ROC curve analysis was used to assess the performance of NT-proBNP to exclude cardiac abnormalities. The upper limit of the lowest tertile of NT-proBNP was used as a cut-off value.. NT-proBNP levels were associated with abnormal left ventricular (LV) dimensions, LV systolic and diastolic function, left atrial enlargement and valvular heart disease. LV mass, E/A ratio and degree of aortic regurgitation were identified as independent predictors of NT-proBNP. NT-proBNP levels were higher with greater number of echocardiographic abnormalities (P < 0.001). A cut-off level of 269.5 pg/mL identified patients with abnormal LV dimensions or depressed LV systolic function (sensitivity 85%, negative predictive value (NPV) 77%, area under the curve 0.75 (95% CI 0.64-0.85)). In addition, high NPV were found for LV systolic dysfunction, left atrial enlargement, severe valvular heart disease and pulmonary hypertension. The test performance of NT-proBNP to exclude any echocardiographic abnormality showed a sensitivity of 82% and a NPV of 65%.. In this convenience sample of well-functioning nonagenarians NT-proBNP was related to a wide variety of functional and structural echocardiographic abnormalities. Moreover, NT-proBNP could be used to exclude echocardiographic abnormalities in well-functioning nonagenarians and might be used to indicate who needs to be referred for further cardiovascular examination.

Topics: Age Factors; Aged, 80 and over; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Cardiac resynchronization therapy (CRT) has been proven its value in adult patients with congestive heart failure of low ejection fraction and wide QRS duration. Contrast to adult patients, CRT has been rarely applied for young patients. We report on a 9-yr-old boy with progressive left ventricular (LV) dilatation and dysfunction following chronic VVI pacemaker therapy for congenital complete atrioventricular block associated with maternal anti-SSA/Ro and SSB/La antibody. His LV dysfunction was improved after epicardially established CRT.

Topics: Antibodies, Antinuclear; Atrioventricular Block; Cardiac Pacing, Artificial; Cardiac Resynchronization Therapy; Child; Chronic Disease; Electrocardiography; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Radiography; Sjogren's Syndrome; Ventricular Dysfunction, Left

To investigate the clinical features of severe chronic heart failure patients with normal B-type natriuretic peptide (BNP).. A total of 57 patients with severe chronic heart failure (New York Heart Association class III and IV) were included in this prospective control study from Dec. 2002 to Oct. 2009. Group A included 13 patients with normal BNP (< 100 ng/L) and group B included 44 patients with increased BNP (> 100 ng/L). Group A patients were followup for (19.6 ± 14.7) months and group B patients for (72.5 ± 17.1) months.. The baseline clinical characteristics of two groups were comparable. Left ventricular end diastolic diameter (LVEDd) of group A was larger than group B [(70.56 ± 4.33) mm vs.(63.73 ± 3.75) mm, P < 0.05], the left ventricular ejection fraction (LVEF) of group A was lower than group B [(24.16 ± 2.50)% vs. (28.49 ± 2.63)%, P < 0.05]. The number of patents tolerating metoprolol in group A is lower than in group B (7/13 vs. 39/44, P < 0.05), and the tolerant dose of metoprolol in group A is lower than in group B [(12.5 ± 6.25) mg/d vs. (24.20 ± 11.22) mg/d, P < 0.05]. The level of BNP in group B were significantly higher at acute stages than at remission stages [(962.73 ± 165.00) ng/L vs. (876.24 ± 167.70) ng/L, P < 0.05], but remained unchanged in group A [(74.03 ± 11.18) ng/L vs. (71.38 ± 11.68) ng/L, P > 0.05]. The mortality of group A was higher than group B (11/12 vs. 6/44, P < 0.05). The binary logistic regression analysis (backward) showed that normal B-type natriuretic peptide was an independent predictor of cardiovascular mortality in patients with severe chronic heart failure (OR = 45.488, 95%CI = 5.322 - 388.791).. Normal BNP in patients with severe chronic heart failure suggests the exhaustion of BNP secretion and associated poor prognosis.

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies

Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described.. To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil.. From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels.. Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male). The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR) of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001). Brain natriuretic peptide serum levels were elevated in 19 of 27 patients.. In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for pulmonary thromboendarterectomy had a hemodynamically severe status and had elevated brain natriuretic peptide serum levels. There was a predominance of females in our cohort, and the prevalence of hematological disorders and schistosomiasis was low (less than 10%).

Topics: Adult; Brazil; Cardiac Output, Low; Chronic Disease; Endarterectomy; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism; Schistosomiasis; Sex Distribution; Sex Factors; Vascular Resistance

B-type natriuretic peptide (BNP) is a diagnostic and prognostic marker in heart failure (CHF) patients.. To assess the relation between BNP, diastolic function and exercise capacity in CHF patients.. Fifty CHF patients underwent cardiopulmonary exercise testing. BNP levels were determined at baseline and at peak exercise. Patients were divided in two groups: with lower (<14 ml/kg/min) or higher (>or=14 ml/kg/min) peak oxygen consumption (VO(2)).. Seventeen patients with lower peak VO(2) showed larger incidence of restrictive pattern of the transmitral flow (7/17 vs 4/33, p =0.036). E/Ea ratio was inversely related with peak VO(2) (r =-0.419, p =0.004) and directly related with BNP levels at baseline (r =0.449, p =0.001) and at peak exercise (r =0.475, p =0.001). LV ejection fraction was similar in the two groups. Independent predictors of exercise tolerance were E/Ea ratio (p =0.003), lg BNP at baseline (p =0.034) and increase in lg BNP during exercise (p =0.038).. In CHF patients, E/Ea ratio is a predictor of exercise tolerance and is related with BNP level at rest and at peak exercise.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Oxygen Consumption; Predictive Value of Tests; Prognosis; Prospective Studies; Stroke Volume; Ventricular Function, Left

This study examined the potential association between skeletal muscle histological findings and circulating levels of N-terminal Atrial natriuretic peptide (NT-proANP) and N-terminal B-type natriuretic peptide (NT-proBNP) at rest and during exercise in patients with moderate chronic heart failure. We report a significant correlation between muscle fibre roundness, defined as ratio of fibre perimeter squared to fibre area, and plasma levels of N-BNP. This finding suggests that the degree of intrafibrillar edema is related to the secretion of NT-proBNP.

Topics: Aged; Chronic Disease; Heart Failure; Humans; Male; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain

Reduced glomerular filtration rate (GFR) is strongly associated with reduced survival in patients with chronic heart failure (CHF). Our aim was to determine different pathophysiologic markers that are associated with reduced renal function in CHF.. We studied 86 patients with CHF (58+/-12 years, 78% male). GFR and renal blood flow (RBF) were determined by (125)I-Iothalamate and (131)I-Hippuran clearances. Filtration fraction (FF) was calculated. We determined haemoglobin levels, endothelial function, inflammatory status, plasma renin activity (PRA) and N-terminal pro brain natriuretic peptide (NT-proBNP). Urinary albumin excretion (UAE) was measured in 24 h urine. Mean GFR was 74+/-28 ml/min/1.73 m(2). GFR was strongly related to RBF (r=0.915, P<0.001), FF (r=0.546, P<0.001), but only weakly to endothelial function and PRA. In multivariate analysis, RBF (r=0.938, P < 0.001), FF (r=0.786, P < 0.001) and haemoglobin levels (r= -0.520, P<0.001) were independently associated with GFR. UAE was mainly dependent on RBF (r= -0.401, P < 0.001) and increased exponentially with decreasing RBF. RBF was mainly associated with NT-proBNP (r= -0.561, P<0.001) and PRA (r= -0.422, P<0.001).. Reduced GFR is mainly dependent of decreased RBF in patients with CHF. Endothelial function and neurohormonal activation showed only mild associations with GFR. NT-proBNP showed a strong relationship with RBF, and may be used as a marker of reduced renal perfusion.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chronic Disease; Endothelial Cells; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Renal Circulation; Renin; Renin-Angiotensin System; Risk Factors

Concentrations of B-type natriuretic peptides (BNPs), including N-terminal pro-B-type natriuretic peptide (NT-proBNP), can be used to estimate prognosis in chronic heart failure. Large biologic variability, however, limits the usefulness of serial measurements in individual patients. As a result, the magnitude of change in peptide concentrations that is clinically meaningful remains to be established.. We studied 172 New York Heart Association class III-IV outpatients. Primary endpoints were death/transplantation or heart failure hospitalization. The magnitude of peptide changes was categorized as no change (<20% increase or decrease from enrollment), > or =20% to < or =80% increase or decrease; and >80% increase or decrease. Changes were also assessed using cutpoints (500 ng/L for BNP and 1000 ng/L for NT-proBNP).. Fifty-two patients died or received transplants during the course of the study. Risk reduction for heart failure hospitalization was demonstrated only for BNP decreases of >80% from enrollment [hazard ratio (HR) 0.318, P = 0.0315]. BNP increases from less than to more than the prespecified cutpoint of 500 ng/L were associated with increased mortality risk (HR 2.101, P = 0.0069), whereas decreases from more than to less than the cutpoint did not reduce risk. NT-proBNP decreases from more than to less than the cutpoint of 1000 ng/L were associated with reduced risk of death/transplantation (HR 0.119, P = 0.0354).. BNP increases from less than to more than the cutpoint were associated with increased risk of events, whereas further increases did not add to risk. In contrast, only substantial natriuretic peptide decreases (>80%) reduced risk. These data suggest that only robust decreases in natriuretic peptide concentrations should be targeted to reduce mortality and heart failure-related hospitalizations.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Biomarkers; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Radioimmunoassay; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Chronic heart failure (CHF) is accompanied by increased adenosine plasma levels (APLs). It is unknown whether adenosine release occurs at the peripheral level or whether the myocardium itself is the source of adenosine release. To answer this question, we evaluated APLs in the coronary sinus of CHF patients during a resynchronisation procedure and compared the values with those at the peripheral level. We also investigated a possible correlation between APLs and ischaemia-modified albumin (IMA) levels, a useful marker of tissue ischaemia.. 19 men and seven women were prospectively included. Blood samples for APLs were collected simultaneously from a brachial vein (peripheral) and from the coronary sinus. Blood samples for brain natriutretic peptide (BNP) and IMA were collected from a brachial vein.. APLs from the brachial vein were higher than those from the coronary sinus (1.69 vs 0.75 muM p<0.01). IMA levels were correlated with APLs from the brachial vein (r = 0.59, p<0.01). BNP concentrations were correlated with APLs from the brachial vein (r = 0.73, p<0.001) but not with APLs from the coronary sinus (r = 0.38, p>0.05). BNP concentrations and IMA levels were correlated (r = 0.71, p<0.001).. In CHF patients, adenosine release occurs at a peripheral level and not at the myocardium level.

Topics: Adenosine; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Coronary Sinus; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Serum Albumin; Troponin I

The Duke Activity Status Index (DASI) provides an accurate estimate of functional capacity in patients with chronic heart failure (HF). The aim of this study was to evaluate the prognostic value of the DASI against well-established prognostic factors in 130 consecutive patients hospitalized for worsening HF symptoms (mean age 64 +/- 12 years, mean left ventricular ejection fraction 26 +/- 7%), followed for 9 months for major cardiovascular events, defined as death or hospitalization for HF decompensation. During follow-up, 77 of 130 patients (59%) experienced major cardiovascular events after a median time of 60 days (range 5 to 220). Patients with eventful courses were in higher New York Heart Association functional classes (p = 0.001) and had shorter 6-minute walking distances (p = 0.041), lower ejection fractions (p <0.001), higher plasma B-type natriuretic peptide (BNP) levels at hospital admission and discharge (both p <0.001), and lower DASI scores (16 +/- 12 vs 25 +/- 17, p = 0.003). In multivariate Cox regression analysis including all these variables, only BNP level at discharge (p = 0.006) and DASI score (p = 0.047) were independently associated with event-free survival. A BNP cutoff of 697 pg/ml predicted future events with 59% sensitivity and 86% specificity, while a DASI score cutoff of 8 had 76% sensitivity and 25% specificity. The combination of the 2 cutoffs predicted events with 33% sensitivity and 95% specificity. Event-free survival was significantly lower in patients with the 2 markers positive (BNP >697 pg/ml and DASI score <8) compared with those with with 2 markers negative (63 +/- 27 vs 183 +/- 15 days, log-rank p <0.0001). In conclusion, functional status assessment by the DASI bears prognostic value, and its combination with plasma BNP may provide quite specific risk stratification in patients with chronic HF.

Topics: Activities of Daily Living; Cardiomyopathy, Dilated; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Stroke Volume; Ventricular Function, Left

It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process-possibly affecting the prognostic power-of NT-proBNP-or reflect age-related subclinical pathological changes.. To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF).. Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443).. University hospital outpatient departments in the UK and Germany.. Chronic stable heart failure due to systolic left ventricular dysfunction.. None.. All-cause mortality.. In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09).. NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient.

Topics: Age Factors; Aged; Biomarkers; Chronic Disease; Epidemiologic Methods; Female; Germany; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Prognosis; United Kingdom; Ventricular Dysfunction, Left

Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long-term prognostic value in CHF outpatients.. Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64+/-12 years, mean ejection fraction 27+/-7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-alpha, soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ-summary (KCCQ-s<50) score had lower 6MWT (P<0.05), and higher BNP (P<0.05) and pro-inflammatory markers (P<0.05) than those with KCCQ-s>or=50. Worse health status was also associated with shorter event-free survival (115+/-12 days for KCCQ-s<50 vs. 214+/-15 days for KCCQ-s>or=50, P=0.0179). Separating patients according KCCQ-functional score (KCCQ-f, cut-off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR=0.637, 95% CI 0.450-0.900, P=0.011) and KCCQ-f (HR=0.035, 95% CI 0.002-0.824, P=0.037) were independent predictors of event-free survival at 250 days.. KCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ-f is an independent predictor of long-term event-free survival in CHF.

Topics: Attitude to Health; Biomarkers; Chronic Disease; Depression; Disease-Free Survival; Female; Health Status; Heart Failure; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Surveys and Questionnaires; Walking

Attenuation of the effects of natriuretic peptides has been demonstrated in animal models but studies in humans are scarce, particularly concerning renal attenuation. We investigated the attenuation of B-type natriuretic peptide (BNP) in chronic advanced heart failure (HF).. We included 62 outpatients with HF and severe left ventricular systolic dysfunction. Cases had at least one hospital admission or emergency department visit for acute HF in the previous year and were in NYHA class III/IV despite optimized therapy. The individual age- and sex-matched controls were symptomatically controlled (NYHA I and II). We collected 24 h urine and a blood sample from all patients. Plasma BNP and plasma (pcGMP) and urine cyclic guanosine monophosphate (ucGMP) were measured. Patients were followed for 3 months for hospital admission or all-cause death. ucGMP to plasma BNP (ucGMP/BNP) ratio was attenuated in cases vs. controls [median (IQR): 8354 (4293-16,456) vs. 12,693 (6896-22,851)]. There were no differences in pcGMP to BNP (pcGMP/BNP) ratio or urine cGMP excretion. Patients with worse outcome had lower pcGMP/BNP [260 (86-344) vs. 381 (244-728) in patients without adverse outcome events] and lower ucGMP/BNP [4146 (2207-9363) vs. 10,922 (7495-19,971)].. Renal NP's second messenger production is attenuated in advanced HF. Patients with worse outcome have lower ucGMP/BNP and pcGMP/BNP ratios.

Topics: Aged; Chronic Disease; Creatinine; Cyclic GMP; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Second Messenger Systems; Ventricular Dysfunction, Left

Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses.. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60).. We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Chronic Disease; Epinephrine; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Prognosis; Survival Rate

Chronic thromboembolic pulmonary hypertension (CTPH) is a potential complication of pulmonary embolism (PE). Only few studies have assessed the role of brain natriuretic peptide (BNP) in patients with chronic pulmonary hypertension, and there are no data on the potential utility of BNP as a preclinical biomarker of CTPH. To assess the correlation between pulmonary artery systolic pressures (PAPs) and amino terminal proBNP (Nt-proBNP) and its value in the diagnosis of CTPH in patients with previous PE. Patients were evaluated with echocardiography at least 6 months after the index event. Pulmonary hypertension was defined as PAPs > or =40 mmHg at rest. Each subject underwent measurement of Nt-proBNP. Forty-nine patients were enrolled (mean age 64.5 +/- 13.1 years; 22 men). Seven patients had CTPH, and two were symptomatic. There was a good correlation between PAP on echocardiography and Nt-proBNP (r 0.64; P = 0.00003). Nt-proBNP was elevated in 6 of 7 patients [sensitivity: 85.7%; 95% confidence interval (CI): 48.7, 97.4] and it was normal in 35 of 42 patients without CTPH (specificity: 76.2%; 95% CI: 61.5, 86.5%). Six of the 13 patients with high Nt-proBNP levels had CTPH, whereas 1 of 36 patients with normal Nt-proBNP levels had pulmonary hypertension. The resulting positive predictive value was 46.1% (95% CI: 19.2, 74.9), and the negative predictive value was 97.2% (95% CI: 85.5-99.9). In conclusion, Nt-proBNP correlates with PAPs and may be used to exclude preclinical or symptomatic CTPH in patients with previous PE. Prospective studies on a larger population are warranted to confirm our preliminary findings.

Topics: Aged; Biomarkers; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism

Brain natriuretic peptide (BNP) and N-Terminal pro natriuretic peptide (NT-proBNP) are widely accepted to diagnose congestive heart failure (CHF) in the emergency room. The aim of this study was to evaluate the value of BNP and NT-proBNP to diagnose CHF in primary care.. Clinical and Doppler-echocardiographic assessment of patients referred by their general practitioner (GP) with the diagnosis of CHF. Receiver operating curves were used to evaluate the accuracy of BNP and NT-proBNP for echocardiographically confirmed systolic and/or diastolic heart failure.. Three hundred and eighty four patients (mean age of 65) were included. One hundred and ninety three (50%) patients had systolic heart failure and 31 (8%) had isolated diastolic heart failure. Using currently recommended cut-off values of BNP (less than 100 pg/ml) and NT-proBNP (less than 125 pg/ml) for exclusion of CHF, BNP was false negative in 25% and NT-proBNP in 10% of the patients. The area under the curve was better for NT-proBNP than for BNP (0.742 vs. 0.691).. In this population with a high prevalence of CHF, BNP and NT-proBNP failed to adequately rule out CHF. GP's should be cautious when using BNP and NT-proBNP in primary care. An echocardiography remains compulsory in unexplained dyspnea.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Dyspnea; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Prospective Studies; Referral and Consultation; ROC Curve; Switzerland; Treatment Outcome

Although there is substantial interest in the use of newer biomarkers to identify patients with chronic heart failure (CHF), recently few investigations have evaluated the incremental usefulness of multiple conventional biomarkers. Combination of several biomarkers simultaneously could enhance risk stratification in CHF.. We analyzed 7 biomarkers (brain natriuretic peptide, uric acid, sodium, hemoglobin, creatinine, creatinine clearance, high-sensitivity C-reactive protein), which were known as established prognostic markers for CHF, in 154 consecutive CHF patients, and patients were prospectively followed with endpoints of cardiac death or re-hospitalization. When there was an abnormal value, we scored it for one point to calculate multimarker score. Patients were categorized into 3 strata according to multimarker score. There were 83 cardiac events during the follow-up period. A Cox proportional hazard model showed that patients in the high stratum were associated with the highest risk of cardiac events among the 3 strata. Kaplan-Meier analysis revealed that patients in the high stratum had a significantly higher cardiac event rate compared with lower strata.. The combination of conventional biomarkers could potentially improve the risk stratification of CHF patients for the prediction of cardiac events with low cost and wide availability.

Topics: Aged; Biomarkers; C-Reactive Protein; Chronic Disease; Creatinine; Female; Follow-Up Studies; Heart Failure; Hemoglobins; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Sodium; Uric Acid

Neurohormones are involved in the physiopathology of heart failure, but little is known about its behavior in significant chronic aortic regurgitation (AR). We aimed at analyzing the behavior of these mediators in AF.. We aimed at analyzing the behavior of these mediators in AF.. We analyzed 89 patients with AF, whose mean age was 33.6+/-11.5 years and of whom 84.6% were males, 60% asymptomatic, all with rheumatic etiology. After the clinical and echocardiographic assessment, plasma measurements of tumor necrosis factor (TNF), soluble TNF receptor types I and II (sTNFRI e sTNFRII), interleukin-6 (IL-6), its soluble receptor (sIL6R), endothelin-1 and B-type natriuretic peptide (BNP) were carried out; 12 healthy individuals were used as controls.. The mean values of the left ventricle diastolic diameter (LVDD) were 71.9+/-8.3mm, whereas the mean values of the LV systolic diameter (LVSD) were 50.4+/-9.3mm. The neurohormonal levels were elevated in patients with AF (TNF 92.65+/-110.24 pg/mL vs. 1.67+/-1.21 pg/ml in controls, p<0.001), (IL-6 7.17+/-7.78 pg/ml vs. 0.81+/-0.38 pg/mL in controls, p=0.0001) and TNFRI (894.75+/-348.87 pg/mL vs. 521.42+/-395.13 pg/ml, p=0.007). Except for the BNP levels, symptomatic and asymptomatic patients presented a similar neurohormonal profile. There was a correlation between TNFRII and LVDD (r=-0.329, p=0.038) and LVSD (r=-0.352, p=0.027). BNP levels were significantly higher in symptomatic patients and only in the latter it was possible to establish a correlation between BNP and ventricular diameters.. Patients with significant chronic AF present high neurohormonal levels, with no correlation with the symptomatic status. The TNFRII and BNP levels could be correlated with ventricular diameters, but only the latter could be correlated with symptoms.

Topics: Adult; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Interleukin-6; Male; Natriuretic Peptide, Brain; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Patients with a high plasma adiponectin have a poor prognosis in chronic heart failure (CHF). Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are reported to increase the plasma adiponectin concentration, but the effect of beta-blockers on plasma adiponectin in patients with CHF remains unknown.. Blood samples were collected at before and 6 months after administration of carvedilol in 44 CHF patients. The hemodynamic parameters, echocardiography, plasma concentrations of brain natriuretic peptide (BNP), norepinephrine and adiponectin were measured. Six months after treatment, there were significantly decreased plasma concentrations of adiponectin (15.8 +/-1.4 to 11.0 +/-1.1 microg/ml, P<0.0001), BNP and norepinephrine and increased left ventricular ejection fraction (LVEF). On stepwise multivariable analyses, a higher plasma adiponectin concentration before treatment (rs=-0.561, P<0.0001) was a significant independent predictor of a greater decrease in adiponectin concentration and the decrease in plasma adiponectin concentration was significantly correlated with the improvement of LVEF (r=-0.561, P<0.0001).. These findings indicate that carvedilol decreases plasma adiponectin concentration and that the decrease in plasma adiponectin is associated with the improvement of LVEF after treatment with carvedilol in CHF patients.

Topics: Adiponectin; Adrenergic beta-Antagonists; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Propanolamines; Severity of Illness Index; Stroke Volume; Tumor Necrosis Factor-alpha

Because both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) competitively bind to natriuretic peptide receptors but not N-terminal proBNP (NT-proBNP), the diagnostic value of BNP as a marker of the severity of heart failure in comparison with NT-proBNP during exogenous ANP (carperitide) infusion remains unclear. Forty-two patients with CHF (NYHA class III or IV) treated with the infusion of carperitide were included in the present study. We measured plasma levels of BNP and NT-proBNP at baseline and after the improvement of symptoms. We also measured these parameters before and 1 hour after stopping the infusion of carperitide. After stopping the infusion of carperitide, the plasma BNP level was significantly decreased by about 20% (394 +/- 53.8 versus 312.8 +/- 46 pg/mL, P < 0.0001) but plasma NT-proBNP did not change (1674.5 +/- 282.1 versus 1777.5 +/- 300.3 pg/mL, P = 0.259). The molar ratio of plasma BNP/NT-proBNP was significantly higher during carperitide infusion (0.74 +/- 0.08) than those at baseline (0.63 +/- 0.06) and after stopping carperitide (0.59 +/- 0.07). During carperitide infusion, plasma NT-proBNP may be a more reliable marker of endogenous cardiac natriuretic peptides than plasmaBNP, which may be increased by carperitide infusion.

Topics: Algorithms; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Diagnosis, Differential; Female; Heart Failure; Humans; Infusion Pumps; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome

Although cardiac output index (CI), stroke volume index (SVI), and total systemic vascular resistance (TSVR) are important hemodynamic parameters for the prognosis of chronic heart failure (CHF), they are difficult to measure in an outpatient setting. Whole body bioimpedance monitoring using a Non-Invasive Cardiac System (NICaS) allows for easy, non-invasive estimation of these parameters. Here, whether NICaS-derived hemodynamic parameters are clinically significant was investigated by relating them to other conventional cardiovascular functional indices, and by evaluating their predictive accuracy for CHF readmission.. Study subjects of 68 patients with CHF were enrolled in the study immediately upon discharge from the hospital. NICaS-derived CI, -SVI, and -TSVR values obtained at an outpatient clinic were significantly related with left ventricular ejection fraction (LVEF) measured by echocardiography, serum B-type natriuretic peptide (BNP), and exercise tolerance. During the 100 +/-98 days follow-up, 15 patients were readmitted to our hospital for CHF recurrence. Multivariate analysis indicated that LVEF, NICaS-derived CI, NICaS-derived SVI, and plasma BNP were significant indicators (receiver operating characteristic curve cut-off point, LVEF: 37%, NICaS-derived CI: 2.49L x min-1 x m(-2), NICaS-derived SVI: 27.2 ml/m(2), plasma BNP: 344 pg/ml) for readmission.. Hemodynamic parameters derived by NICaS are applicable for the non-invasive assessment of cardiac function in outpatient CHF follow up.

Topics: Aged; Cardiac Output; Chronic Disease; Electric Impedance; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Monitoring, Physiologic; Multivariate Analysis; Natriuretic Peptide, Brain; Outpatients; Prognosis; Stroke Volume; Vascular Resistance

In this study, circulating levels of proinflammatory and anti-inflammatory mediators are studied in patients with chronic heart failure (CHF) in China. Sixty-five patients with CHF and 32 control subjects are studied. The proinflammatory and anti-inflammatory cytokines interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in plasma are determined by immunoradiometric assay kits. Catecholamine (CA) in plasma is evaluated by high-performance liquid chromatography. Plasma levels of IL-6, IL-10, TNF-alpha, ANP, BNP, and CA in CHF patients are significantly higher than those in control subjects. Patients in a higher New York Heart Association (NYHA) class show higher concentrations of inflammatory mediators than those in a lower NYHA class, although the ratio of plasma IL-10 to TNF-alpha in patients with CHF is significantly lower than in the control group. It is concluded that proinflammatory and anti-inflammatory cytokine levels are increased and IL-10/TNF-alpha is decreased in Chinese patients with CHF.

Topics: Atrial Natriuretic Factor; Catecholamines; China; Chromatography, High Pressure Liquid; Chronic Disease; Cytokines; Female; Heart Failure; Humans; Immunoradiometric Assay; Inflammation Mediators; Interleukin-10; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Tumor Necrosis Factor-alpha

Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD.. In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification > or =100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment.. FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.

Topics: Aged; C-Reactive Protein; Calcinosis; Chronic Disease; Comorbidity; Coronary Occlusion; Cross-Sectional Studies; Diabetes Mellitus; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Phosphates; Radiography; Single-Blind Method; Ultrasonography; Vitamin D

It is difficult to evaluate the tolerance to anesthesia of patients undergoing operations, who have risk factors of congestive heart failure, such as hypertension, old age or various cardiac diseases. BNP (B type natriuretic peptide) is a useful biomarker as a screening tool for LV dysfunction. Therefore we hypothesized that the measurement of BNP may be useful for perioperative management of these patients.. Subjects were 101 (58 male and 43 female) gastro-intestinal cancer patients, aged 30 to 91 years (mean 63.9 +/- 12.4) scheduled for intraperitoneal surgery. All patients' plasma BNP concentrations were measured when the patient agreed to the operation. Forty-five patients were enlisted for remeasurements on 2 or 4 postoperative days. We checked patients' backgrounds, perioperative circulatory characteristics and cardiac events. The relationship of BNP to other characteristics and cardiac events were analyzed.. The preoperative mean BNP of patients under 55 years of age (n=20) was 20.4, in patients age 55 to 74 (n=60) it was 30.4, and in patients 75 years and over (n=21) it was 162.1. BNP in elderly patients was higher than in the younger. The mean BNP of the 44 patients with some complications (hypertension, ECG abnormality, cardiac disease etc.) was 97.8, as compared to 23.3 in the 57 patients without complications. The BNP was higher in patients who were elderly, had some cardiac disease, lower exercise capacity, chest X ray abnormality or who needed an echo cardiographic examination. Among the 45 patients who were checked pre and postoperatively, 19 patients' BNP increased postoperatively, while 26 patients showed no change or decrease. Excluding 2 patients, with newly onset congestive heart failure during the postoperative period, the preoperative mean BNP was 63.5, and the postoperative mean BNP was 54.6. During the perioperative period, there was no significant change of BNP. There was no relationship between the BNP and perioperative circulatory characteristics or cardiac events. There were 5 cases with high BNP levels (> 300). None of these patients had cardiac symptoms, and they had normal LV systolic function. It is probable that these patients had chronic heart failure due to LV diastolic dysfunction and risks of perioperative heart failure.. We cannot predict any circulatory characteristics and cardiac events from preoperative BNP measurement; however BNP measurement is useful for screening asymptomatic chronic heart failure due to LV diastolic dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia; Biomarkers; Chronic Disease; Digestive System Neoplasms; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Perioperative Care; Postoperative Complications; Risk Factors; Ventricular Dysfunction, Left

Topics: Adiponectin; Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Severity of Illness Index; Stroke Volume; Tumor Necrosis Factor-alpha

Topics: Chronic Disease; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism

Chronic mitral regurgitation (MR) results in volume overload followed by left ventricular (LV) and left atrial remodeling. The aim of this study was to investigate the relation of clinical, echocardiographic findings and N-terminal B-type natriuretic peptide (NT-proBNP) to LV reverse remodeling (LVRR) early after valve repair for severe chronic MR concomitant with modified maze procedure for atrial fibrillation (AF).. We retrospectively evaluated 60 patients who were surgically treated for severe chronic MR and AF. Plasma NT-proBNP and echocardiographic measurements were performed before surgery, before discharge and 12 months after surgery. Echocardiogram was additionally performed at 6 months. LVRR was assessed by looking at regression of LV mass index (LVMI) using echocardiography.. Fifty-two patients (87%) were classified in the LVRR group, defined as having a postoperative reduction in LVMI. The remaining patients were classified in the non-LVRR group. The non-LVRR group was older (p = 0.004), had a significantly higher ratio of patients with hypertension (p = 0.022), higher NT-proBNP levels (p = 0.007) and lower ejection fraction (p = 0.034) compared to the LVRR group. In multivariate analysis, age (odds ratio 0.874, p = 0.013) and NT-proBNP levels (odds ratio 0.185, p = 0.040) were independent predictors of LVRR.. Preoperative lower NT-proBNP levels and younger age may predict LVRR early after surgical correction of chronic MR with AF.

Topics: Age Factors; Aged; Atrial Fibrillation; Catheter Ablation; Chronic Disease; Cohort Studies; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Preoperative Care; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival Analysis; Treatment Outcome; Ventricular Remodeling

To determine plasmic concentrations of NT-proBNP, TNFalpha and IL-6 in patients with coronary heart disease (CHD) complicated with chronic cardiac failure (CCF); to compare these parameters with hemodynamic and functional ones.. A total of 157 CHD patients (84.1% males, mean age 54.3 +/- 6.8 years) were divided into 3 groups matched by sex and age according to the presence of CCF and left ventricular (LV) or systolic dysfunction.. CCF patients with LV dysfunction or intact LV function had much higher plasmic concentrations of neurohumoral mediators than CHD patients without CCF. A plasmic NT-proBNP level over 1000 fmol/ml was associated with a 5.5-fold increase in the relative risk of LV diastolic dysfunction for CCF patients (rR 5.6; 95% CI 1.4-30.0; p = 0.0065) while an IL-6 level over 6.1 pg/ml was associated with a 9-fold increase in this risk (rR 8.9; 95% CI 2.3-35.4; p = 0.00001). Plasmic NT-proBNP and IL-6 levels went up in correlation with a CCF functional class. A plasmic level of TNFalpha correlated with anginal functional class.. Changes in plasmic levels of the above neuromediators are associated with changes in some LV function and functional parameters of CCF patients.

Topics: Biomarkers; Chronic Disease; Echocardiography; Female; Heart Failure; Hemodynamics; Humans; Interleukin-6; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

Urinary excretion is currently regarded as the main mechanism of elimination of N-terminal prohormone brain natriuretic peptide (NT-proBNP). The clinical implications and the value of measurement of urinary NT-proBNP in patients with heart failure are largely unknown.. We studied 94 patients (age, 58+/-11 years; 79% men) with chronic heart failure (CHF) and 20 age- and sex-matched healthy control subjects. Glomerular filtration rate and effective renal plasma flow were measured as clearance of (125)I-iothalamate and (131)I-hippuran, respectively. NT-proBNP levels were determined in both plasma and 24-hour urine collections. Mean left ventricular ejection fraction of CHF patients was 0.28+/-0.09. Plasma NT-proBNP levels were higher in CHF patients compared with control subjects (median, 547 versus 41 pg/mL; P<0.001). Urinary NT-proBNP excretion, however, was substantially lower in CHF patients (median, 0.13 versus 2.3 mL/min; P<0.001). Urinary NT-proBNP excretion was independent of estimated glomerular filtration rate. In both CHF patients and control subjects, there was a strong and inverse relation between plasma NT-proBNP concentrations and urinary NT-proBNP excretion (r=-0.72 and r=-0.65 respectively; both P<0.001). Decreased renal plasma flow in CHF was significantly associated with a lower excretion of NT-proBNP (P=0.026).. Urinary NT-proBNP excretion is lower in patients with CHF compared with control subjects and is inversely related to plasma NT-proBNP. Urinary NT-proBNP is associated with renal plasma flow but not with estimated glomerular filtration rate. Elevated levels of plasma NT-proBNP in patients with CHF might be explained not only by myocardial stress but also by a marked decrease in urinary excretion.

Topics: Aged; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Iodine Radioisotopes; Iothalamic Acid; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Radionuclide Imaging; Renal Circulation; Renal Insufficiency; Urine

This study was designed to quantify the crude and adjusted effects of estimated glomerular filtration rate (eGFR) on N-terminal-pro-brain-natriuretic peptide (proBNP) measured with three immunoassays and brain natriuretic peptide (BNP) in elderly individuals.. Cross-sectional study.. 474 elderly outpatients with suspected heart failure (prevalence 13%) from the primary care.. The effects of eGFR on proBNP, measured with three different immunoassays (Roche Diagnostics, Oslo and Copenhagen), and BNP (Shionogi) concentrations were evaluated by multiple linear regression models.. In univariate analyses the effect of a 10% decrease in eGFR on proBNP concentrations was a 15% (95% confidence interval 11% to 18%), 9% (5% to 13%) and 21% (14% to 28%) increase. In multivariate models the effect was a 7% (3% to 11%), 4% (2% to 6%) and 13% (4% to 20%) increase. The effect of a 10% decrease in eGFR on BNP concentrations (Shionogi) was a 10% (5% to 15%) (univariate) and a 4% (1% to 9%) (multivariate) increase.. The effect of eGFR on proBNP measured with three different immunoassays and BNP is modest and within the same range. The effect of eGFR on proBNP and BNP concentrations is reduced substantially after adjustment for important clinical and echocardiographic confounders. These findings should be considered before renal function is offered as an explanation for increased proBNP or BNP levels.

Topics: Aged; Aged, 80 and over; Chronic Disease; Cross-Sectional Studies; Glomerular Filtration Rate; Heart Failure; Humans; Immunoassay; Kidney Diseases; Natriuretic Peptide, Brain; Peptide Fragments

The purpose of the study was to determine the independent and additive prognostic value of brain natriuretic peptide (BNP) in patients with severe asymptomatic mitral regurgitation and normal left ventricular function.. Early surgery could be advisable in selected patients with chronic severe mitral regurgitation, but there are no criteria to identify candidates who could benefit from this strategy. Assessment of BNP has not been studied in asymptomatic patients with severe mitral regurgitation; hence, its prognostic value remains unclear.. We prospectively evaluated 269 consecutive patients with severe asymptomatic organic mitral regurgitation and left ventricular ejection fraction above 60%. The first 167 consecutive patients served as the derivation cohort, and the following 102 patients served as a validation cohort. The combined end point was the occurrence of either symptoms of congestive heart failure, left ventricular dysfunction, or death at follow-up.. The end point was reached in 35 (21%) patients of the derivation set and in 21 (20.6%) patients of the validation cohort. The receiver-operating characteristics curve yielded an optimal cutoff point of 105 pg/ml of BNP that was able to discriminate patients at higher risk in both cohorts (76% vs. 5.4% and 66% vs. 4.0%, respectively). In both sets, BNP was the strongest independent predictor by multivariate analysis.. Among patients with severe asymptomatic organic mitral regurgitation, BNP > or =105 pg/ml discriminates a subgroup of patients at higher risk. Because of its incremental prognostic value, BNP assessment should be considered in clinical routine workup for risk stratification.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Radioimmunoassay; Reproducibility of Results; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Topics: Biomarkers; Cardiac Surgical Procedures; Chronic Disease; Echocardiography; Follow-Up Studies; Humans; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Severity of Illness Index

To assess the prognostic value of a wide spectrum of neurohormonal and inflammatory markers along with functional status and exercise capacity, in hospitalized chronic heart failure (CHF) patients with depressive symptoms.. A total of 300 consecutive hospitalized CHF patients were screened for depressive symptomatology using the Zung self-rated depression scale (SDS). Patients with depressive symptoms (Zung SDS > or = 40) underwent a 6 min walking test, and evaluation of left ventricular ejection fraction, B-type natriuretic peptide (BNP), and plasma inflammatory/anti-inflammatory factors [interleukin (IL)-6, IL-10, tumour necrosis factor-alpha, soluble intercellular adhesion molecule-1, and vascular cell adhesion molecule-1]. Patients were subsequently followed for up to 1 year for major adverse cardiovascular events (MACE, death or hospitalization due to cardiovascular causes). One hundred and fourteen patients (38%) had a Zung SDS > or = 40. One-year event-free survival of these patients was 19% (mean +/- SE, 150 +/- 12 days). In multivariate analysis, only BNP (HR = 1.001, P = 0.002) and IL-10 (HR = 0.864, P = 0.049) were independent predictors of MACE. Using receiver operator characteristics analysis-derived cut-offs, a BNP value of 290 pg/mL predicted MACE with 86% sensitivity and 69% specificity, whereas an IL-10 value of 5 pg/mL predicted MACE with 61% sensitivity and 78% specificity. Event-free survival differed significantly between patients with BNP < 290 pg/mL and IL-10 > 5 pg/mL (261 +/- 44 days) and those with BNP > 290 pg/mL and IL-10 < 5 pg/mL (79 +/- 11 days, P = 0.0001).. Neurohormonal activation and defective anti-inflammatory properties are independent predictors of long-term outcome in hospitalized CHF patients with depressive symptoms.

Topics: Adult; Aged; Analysis of Variance; Cause of Death; Chronic Disease; Cohort Studies; Cytokines; Depression; Disease-Free Survival; Female; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Interleukin-10; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Probability; Prognosis; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Analysis

The measurement of circulating brain natriuretic peptide (BNP) and its related peptide, the N-terminal fragment of proBNP (NT-proBNP), have a high degree of diagnostic accuracy and clinical relevance both in acute and chronic heart failure (HF). However, the role of measurement of BNP/NT-proBNP in the follow-up of treated HF patients is still debated. In this chapter, authors have studied the clinical impact of B-type natriuretic peptide assay in the follow-up of patients with heart failure, and, in particular, the possible role of the measurement of its circulating levels in guiding the treatment. A relatively small number of randomized studies were designed to specifically evaluate the clinical use of BNP/NT-proBNP assay in monitoring and tailoring the medical therapy in HF patients. A meta-analysis of results reported in these studies indicate that the inefficacy to improve the mortality rate of the peptide-guided compared to the control group found in some studies, may depend on to the inability of current therapeutic strategies to modify prognosis, especially in the elderly subset of patients, who are characterized by more advanced disease and comorbidities. Further prospective and randomized clinical studies are necessary to definitively demonstrate whether BNP/ NT-proBNP-guided therapy is able to significantly improve the outcome of patients with HF.

Topics: Age Factors; Chronic Disease; Heart Failure; Humans; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Sex Factors

The effect of the dose of carvedilol on cardiac sympathetic nerve activity (CSA) and mortality remain uncertain in patients with chronic heart failure (CHF).. To compare the dose of carvedilol and the transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were measured in 107 patients with systolic CHF who received carvedilol. Patients were divided into 2 groups [group I: low dose (<10 mg/day, n=41) and group II: high dose (>or=10 mg/day, n=66)]. There was no difference between the 2 groups for the hemodynamic parameters. The dose of carvedilol did not correlate with plasma NE, but was significantly correlated with the transcardiac increase in NE. During a median follow-up of 4.3 years, 13 patients died of cardiac disease. In the Cox stepwise multivariate analyses, a high level of transcardiac increase in NE (P<0.001), high level of plasma log NT-proBNP (P=0.004) and low dose of carvedilol (P=0.012) were significant independent predictors.. The carvedilol dose is important for the management of CSA and prognosis in patients with systolic CHF.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Biomarkers; Carbazoles; Carvedilol; Chi-Square Distribution; Chronic Disease; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Propanolamines; Proportional Hazards Models; Risk Assessment; Risk Factors; Sympathetic Nervous System; Time Factors; Treatment Outcome

Tumour necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a multifunctional cytokine that has recently been implicated in cardiovascular disease. The aim of this study was to define the plasma levels of sTWEAK in patients with stable chronic heart failure and evaluate the possibility of a prognostic impact of sTWEAK.. sTWEAK levels in plasma samples from 364 patients with systolic heart failure were compared with 36 control patients. The median levels of sTWEAK in heart failure patients were significantly lower than those of the control group (217 pg/mL, interquartile range 136-311 vs. 325 pg/mL, interquartile range 250-394 pg/mL). Moreover, sTWEAK levels were lower in patients with ischaemic cardiomyopathy vs. dilated cardiomyopathy and correlated significantly with functional NYHA class. Patients with plasma levels below a ROC-derived cut-off value of 227 pg/mL had a significantly higher mortality rate after 4 years. Upon univariate and multivariate analyses, sTWEAK levels below 227 pg/mL emerged as an independent predictor of subsequent death.. In contrast to other cytokines shown to be increased in heart failure patients, plasma levels of sTWEAK are significantly reduced in chronic stable heart failure. In addition, lower plasma levels of sTWEAK predict an adverse prognosis independent of established risk markers such as NT-proBNP.

Topics: Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Chronic Disease; Cytokine TWEAK; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Tumor Necrosis Factors

The increasing number of patients with progressive or exacerbated heart failure that is refractory to medical treatment necessitates the development of innovative cardiac assist devices. The aim of this study was to investigate whether a new percutaneously inserted system, which allows continuous aortic flow augmentation (CAFA), could be shown to be clinically effective with neurohormonal benefit in patients admitted with decompensated heart failure. Patients with exacerbations of chronic heart failure were recruited for the study. A percutaneous circulation assist device (Cancion system) promoting CAFA was implanted for up to 4 days in each patient. Clinical improvement was evaluated by measuring the clinical status according to the New York Heart Association (NYHA) classification and biochemical parameters including troponin and B-type natriuretic peptide (BNP) as markers of cardiac necrosis and cardiac overload; these parameters were measured before, during, and after CAFA treatment. The decrease in BNP was determined after implantation, reaching, on average, a maximum decrease of 57% at 72 h (P = 0.04). The neurohumoral response remained significant (P < 0.05) up to 120 h after implantation, with a decrease in BNP levels of 37%, on average, compared to baseline values. Troponin I did not show any significant change during mechanical assistance (P > 0.2). All patients had improved clinical status according to the NYHA classification, and the improvement lasted for more than 1 week. Percutaneous heart-assist devices promoting CAFA offer clinical improvement and a neurohumoral response, with a significant BNP reduction in severe exacerbation of chronic heart failure that is refractory to medical treatment.

Topics: Aged; Aged, 80 and over; Aorta; Biomarkers; Blood Flow Velocity; Chronic Disease; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Troponin I

The use of biomarkers, such as type B natriuretic peptide (BNP, NT pro-BNP) to finely tune the treatment during the follow-up of patients with chronic heart failure is under investigation. The few existing studies published up to now suggest that this approach leads to fewer hospital readmissions and a lower mortality due to heart failure, except in patients over 75 years of age. The positive effects of the use of biomarkers seem to be due to a greater use of target doses of the medications recommended in heart failure (angiotensin converting enzyme, angiotensin receptor blockers, or beta-blockers) and to a better adhesion to guidelines. Thus, it may prove more efficient to develop efforts to increase physicians' adhesion to guidelines than to rely on the dosage of a biomarker.

Topics: Aged; Chronic Disease; Follow-Up Studies; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain

The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress.. We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8+/-1.8 microg/dL versus 12.4+/-0.3 microg/dL, P=0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP (P=0.0003), renin (P=0.002), cortisol (P=0.02), and oxLDL (P=0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol > or =12.5 microg/dL, the hazard ratio of cardiac events in patients with oxLDL > or =12 U/mL was 3.5 compared with that in patients with oxLDL <12 U/mL (P=0.008).. These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Topics: Adrenocorticotropic Hormone; Aldosterone; Biomarkers; Chronic Disease; Diuretics; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Hydrocortisone; Kaplan-Meier Estimate; Linear Models; Lipoproteins, LDL; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Oxidative Stress; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Spironolactone; Time Factors; Treatment Outcome

Thoracic fluid content (TFC) is one of the basic parameters measured by impedance cardiography (ICG). The B-type natriuretic peptide (BNP) is a neuroendocrine mediator produced in the ventricular myocardium and released in response to the increase of wall tension.. To determine the relationship between TFC measured by ICG and BNP serum level in patients with systolic heart failure (HF).. The study population included 50 patients: a group of 30 patients with systolic HF in functional NYHA class II and III [27 males and 3 females, aged 53 +/- 6 years, with mean left ventricular ejection fraction (LVEF) 23 +/- 6%], and 20 controls without HF symptoms and preserved LVEF. The TFC and BNP serum level were measured on the same day.. Mean BNP serum concentration was 521 +/- 882 pg/ml in HF patients and 44 +/- 36 pg/ml in healthy controls (p = 0.02). The TFC values did not differ significantly between the two groups (27.3 +/- 4.5 1/kW in the study group versus 26.3 +/- 2.8 1/kW in control subjects, NS). A significant correlation between TFC and BNP was found in patients with overt HF (r = 0.57, p = 0.001); however, after excluding one patient with exacerbation of HF symptoms, the correlation was non-significant (r = 0.24, p = 0.22). No correlation between these parameters was observed in healthy controls (r = 0.17, p = 0.51).. There was no significant correlation between TFC measured by ICG and BNP serum level in haemodynamically stable patients with HF symptoms. The usefulness of ICG measurements in patients with exacerbated chronic HF needs further investigations.

Topics: Biomarkers; Body Fluids; Cardiography, Impedance; Chronic Disease; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Stroke Volume; Thoracic Cavity

A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in development and progress of heart failure. However, there is limited information about allergic cytokine interleukin-13 (IL-13). The inflammatory responses mediated by allergic cytokines can cause significant morbidity and mortality when they become chronic. Therefore, we elucidated the role of IL-13 in the pathophysiology of chronic heart failure. We measured plasma IL-13 levels by enzyme-linked immunosorbent assay in 110 patients with chronic heart failure and 20 control subjects. Plasma IL-13 levels were increased in heart failure patients, compared with the controls, in association with NYHA functional class. In addition, IL-13 levels were correlated positively with plasma levels of brain natriuretic peptide and C-reactive protein, and negatively with left ventricular ejection fraction. Plasma IL-13 levels may be useful for evaluating disease severity in chronic heart failure.

Topics: Aged; C-Reactive Protein; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Interleukin-13; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index

We evaluated whether right ventricular (RV) diastolic dysfunction assessed by pulsed tissue Doppler imaging (TDI) predicts cardiac events in patients with chronic pulmonary thromboembolism (CPTE).. In 63 consecutive patients with CPTE, early diastolic myocardial velocity (Ea) at the tricuspid annulus by TDI and early diastolic tricuspid inflow (E) by conventional pulsed Doppler were obtained, and E/Ea was calculated as an indicator of RV diastolic dysfunction. Brain natriuretic peptide (BNP) and other echo parameters were also obtained. A cardiac event (rehospitalization caused by congestive heart failure or cardiac death) was the study endpoint. Incidence of cardiac events was determined over a 374+/-451 day follow-up period.. In the follow-up period twelve patients had cardiac events. We divided patients into group A with cardiac events and group B without events. E/Ea was significantly increased in group A as compared with group B (8.3+/-4.1 vs. 5.7+/-2.6, p<0.01). BNP was higher in group A than group B (221+/-191 vs. 121+/-140 mg/dl, p<0.05), and in addition E/Ea was significantly positively correlated with BNP (r=0.48, p<0.001). A logistic regression model for predicting cardiac events was constructed and E/Ea was associated with an increased incidence of cardiac events (relative risk=1.33, 95% CI 1.00-1.75).. Elevated values of E/Ea obtained by TDI may predict cardiac events in patients with CPTE. BNP may also be a significant predictor.

Topics: Adult; Biomarkers; Chronic Disease; Death; Diastole; Echocardiography, Doppler, Pulsed; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Embolism; Ventricular Dysfunction, Right

The aim of this study was to determine if low-dose dobutamine stress echocardiography (LD-DSE) is associated with functional capacity in unselected elderly patients with chronic heart failure.. This was a prospective trial. Thirty five consecutive patients were included, with age >65 years and left ventricular dysfunction (12 ischemic), by blindly assessed LD-DSE and cardiopulmonary exercise testing (CPT). Contractile reserve was defined as a change (D) in wall motion score index (WMSI) = or <0.2 at peak dose dobutamine. At CPT treadmill exercise time, peak VO2, %Vo2 and VE/VCO2 slope were determined. Preserved functional capacity was defined as percent of maximal predicted O2 consumption (%VO2) >80%. Baseline NT-proBNP plasma levels were assessed.. CPT variables were not related to clinical and baseline echocardiography characteristics but were related to DWMSI (exercise time, P=0.004; peak VO2, P=0.008; %VO2, P<0.001; VE/Vco2, P<0.001). Contractile reserve was present in 16 of 17 patients with preserved functional capacity (sensitivity=94%) and in 2 of 13 patients without (specificity=85%). Baseline NT-proBNP levels were lower in patients with contractile reserve (476+/-365 pg/mL) than in those without (1 345+/-1 219 pg/mL) (P=0.019), but were mildly related to CPT variables (P=0.049 and 0.027 with exercise time and %VO2, respectively).. Contractile reserve elicited at LD-DSE is associated with functional capacity in unselected elderly patients with chronic heart failure.

Topics: Adrenergic beta-Agonists; Aged; Chronic Disease; Dobutamine; Echocardiography; Exercise Test; Female; Heart Failure; Humans; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Prospective Studies; Respiratory Function Tests; Ventricular Dysfunction, Left

Excess mortality in patients with chronic kidney disease (CKD) is predominantly due to cardiovascular disease. We explored the prognostic value of biomarkers of cardiac overload [B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and inflammation [high-sensitivity C-reactive protein (hsCRP)] for all-cause mortality in patients with CKD.. Plasma BNP (Siemens Medical Solutions Diagnostics, Frimley, Surrey, UK) and NT-proBNP (Roche Diagnostics PLC, East Sussex, UK), and hsCRP (Siemens Medical Solutions Diagnostics) were measured at study entry. Echocardiograms were undertaken, and left ventricular mass index (LVMI) was calculated. CKD patients (n = 213) were followed for up to 53 months. Kaplan-Meier survival analysis with log-rank testing and hazards ratios (HRs) were calculated for each cardiac biomarker, stratified by respective median values, as a predictor of death to assess outcome.. Fifty-four deaths occurred. NT-proBNP concentration >or=89 pmol/L (HR 5.6, P < 0.0001), BNP concentration >or=14 pmol/L (HR 3.5, P < 0.001), NT-proBNP/BNP ratio >or=6 pmol/pmol (HR 2.6, P < 0.01) and hsCRP concentration >or=4.7 mg/L (HR 2.4, P < 0.01) were unadjusted predictors of death. Only NT-proBNP >or=89 pmol/L (HR 2.5, P < 0.05) and hsCRP >or=4.7 mg/L (HR 1.9, P < 0.05) were independent predictors of death when the HRs were adjusted for significant clinical variables (age, estimated glomerular filtration rate, LVMI and vascular disease).. NT-proBNP and hsCRP can independently predict all-cause mortality in a non-dialysis CKD population and may have a useful role in risk stratification.

Topics: Aged; Biomarkers; C-Reactive Protein; Chronic Disease; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies

Exercise increases natriuretic peptide levels in chronic heart failure (CHF) patients, but the effect is considered minor. We assessed acute and short-term release (<24 h) of NT-proBNP in CHF patients after a maximal cardiopulmonary exercise test (CPET) and 2 different submaximal training sessions.. 102 CHF patients either performed CPET (Group 1), a 1 h endurance (Group 2) or a combined endurance-resistance training session (Group 3). NT-proBNP concentration was determined before, at exercise cessation and after 18-22 h (Protocol A). In 20 patients, samples were obtained before, at exercise cessation, after 15, 30, 45, 60, 90 min, 2, 3, 4, 5, 6, 12, 22 h (Protocol B). Protocol A: At peak exercise, a 15%, 11% and 17% relative increase (p<0.001 vs baseline, all 3 groups) was seen, with a return to baseline after 18-22 h. The increase correlated with indicators of more advanced heart failure. Protocol B: A biphasic pattern was derived with a first peak within 1 h of exercise termination and a second peak (39%, 31% and 33% higher than baseline; p<0.05, all 3 groups) after 4-12 h.. The observed biphasic release of B-type natriuretic peptides supports standardization of sampling, taking recent exercise into account.

Topics: Chronic Disease; Exercise; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Physical Endurance; Resistance Training

B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are biomarkers of cardiovascular disease that is common in patients with chronic kidney disease (CKD). Conflicting data on the influence of glomerular filtration rate (GFR) on BNP and NT-proBNP levels in CKD may stem from failure to account fully for the effects of coexistent cardiac disease, dysfunction, and volume overload.. Prospective head-to-head comparison of plasma BNP and NT-proBNP in ambulatory euvolemic CKD patients with normal LV ejection fraction and no manifest cardiac or vascular disease. GFR was estimated by the Modification of Diet in Renal Disease formula, BNP and NT-proBNP measured using Abbott AxSYM and Roche Elecsys assays, respectively, and cardiac morphology and function assessed by transthoracic echocardiography.. In 142 patients (42% female) of mean age 60 +/- 11 yr, mean left ventricular ejection fraction was 71% +/- 6%, GFR 38 +/- 14 ml/min per 1.73 m(2), and median BNP and NT-proBNP level 59 and 311 pg/ml, respectively. Multivariate predictors of NT-proBNP level were GFR, beta-blocker usage, LV mass index, and hemoglobin level. Plasma BNP was independently predicted by LV mass index and beta-blocker usage but not GFR. In the 74 patients without diastolic dysfunction, there was a significant rise in NT-proBNP but not BNP as GFR declined.. Unlike NT-proBNP, plasma BNP level is relatively independent of GFR. BNP may therefore be the more appropriate biomarker to screen for cardiac dysfunction in CKD.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Models, Biological; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Stroke Volume; Ventricular Function, Left

We evaluated the relation between serum erithropoietin level and the severity of disease and mortality in patients with chronic heart failure (CHF).. We enrolled 96 CHF patients and 50 age- and sex-matched control subjects. Haemoglobin, haemotocrit, N terminal pro-B type natriuretic peptide (NT-proBNP) and erythropoietin levels and echocardiographic parameters were measured. The patients were contacted 1 year after the evaluations to determine survival.. The patients had lower haemoglobin and haematocrit but higher serum erythropoietin and NT-proBNP levels than the control subjects. Serum erythropoietin and NT-proBNP levels increased with worsening functional class. The serum erythropoietin level correlated negatively with left ventricular ejection fraction (r = -0.404, P < 0.001), haemoglobin (r = -0.530, P < 0.001) and haematocrit (r = -0.496, P < 0.001) levels. The patients who died (n = 17) had lower haemoglobin and haematocrit levels and significantly higher erythropoietin and NT-proBNP levels. However, multivariate logistic regression analysis showed that only NT-proBNP level was an independent predictor of mortality (P = 0.002).. Anaemia and resistance to erythropoietin develop proportionately to disease severity and left ventricular systolic dysfunction in patients with CHF. Although serum erythropoietin level seems related with mortality, this observation needs to be confirmed by studies with more patients and longer follow-up.

Topics: Biomarkers; Chronic Disease; Echocardiography; Erythropoietin; Female; Follow-Up Studies; Heart Failure; Hematocrit; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index; Survival Rate; Time Factors; Turkey

Prognostication of patients with chronic heart failure (HF) stabilized by therapy may be difficult. Therefore, the aim was to evaluate whether combined assessment of plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) and Doppler left ventricular (LV) diastolic variables was relevant to the prognosis of patients with stable HF. Outpatients with LV systolic HF (ejection fraction < or =45%), classified using clinical criteria as decompensated (n = 94) and stable HF (n = 219), underwent a complete Doppler echocardiographic study. NT-pro-BNP was measured together with mitral wave velocities, E wave deceleration time, and tissue Doppler early septal annular velocity. Median follow-up was 22 months. Freedom from all-cause mortality or HF hospitalization at 24 months was worst (44%) in patients with decompensated HF, intermediate (58%) in patients with stable HF with NT-pro-BNP higher than the median (>1,129 pg/ml), and best (92%) in patients with lower NT-pro-BNP (log-rank p <0.0001). In patients with stable HF, NT-pro-BNP >1,129 pg/ml (hazard ratio [HR] 2.84, p = 0.003), E wave deceleration time <150 ms (HR 2.31, p = 0.004), and tissue Doppler early septal annular velocity <8 cm/s (HR 2.18, p = 0.01) were predictors of the end point at multivariate analysis. The addition of Doppler LV diastolic variables and NT-pro-BNP significantly improved the chi-square test for outcome prediction (from 14.4 to 46.4). In conclusion, NT-pro-BNP and spectral and tissue Doppler variables of LV diastolic dysfunction added independent and incremental contributions to prognostic stratification of patients with stable HF.

Topics: Aged; Chronic Disease; Diastole; Female; Heart Failure; Heart Septum; Humans; Male; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; ROC Curve; Sensitivity and Specificity; Stroke Volume; Systole; Ultrasonography, Doppler; Ventricular Dysfunction, Left

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chronic Disease; Confounding Factors, Epidemiologic; Humans; Liver Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors

To investigate the relationship between body mass index (BMI) and N-terminal pro-brain natriuretic peptide (NTproBNP) level and resultant prognostic capacity in chronic heart failure (CHF) controlled for known confounders.. We formed 206 triplets of patients (n = 618) with stable systolic CHF matched with respect to age, sex, renal function (MDRD, modification of diet in renal disease formula), and NYHA class, each with a BMI >30 kg/m(2) (group 3), 20-24.9 kg/m(2) (group 1), and 25-29.9 kg/m(2) (group 2). BMI conveys a 4% drop in NTproBNP per unit increase. This influence remained significant after correction for age, sex, MDRD, NYHA, heart rate, rhythm, and ejection fraction. NTproBNP remained an independent predictor of adverse outcome after correction for age, sex, BMI, NYHA, MDRD, and ejection fraction. Despite numerical differences, prognostic power was comparable between BMI groups (log-transformed NTproBNP; group 1: hazard ratio (HR) 1.435, 95% CI 1.046-1.967, chi(2) 5.02, P = 0.03; group 2: HR 1.604, 95% CI 1.203-2.138, chi(2) 10.36, P = 0.001; group 3: HR 1.735, 95% CI 1.302-2.313, chi(2) 14.12, P = 0.0002) (P = NS, all). An NTproBNP correction factor was calculated.. Even matched for NYHA, age, sex, and renal function, BMI exerts a significant and independent inverse influence on NTproBNP in patients with stable CHF. NTproBNP retained equal statistical power in all three BMI groups.

Topics: Biomarkers; Body Mass Index; Chronic Disease; Epidemiologic Methods; Female; Germany; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Registries

Left ventricular diastolic dysfunction has been reported in patients with liver cirrhosis. Although conventional Doppler echocardiography has been used to assess diastolic filling dynamics, this technique is limited in diagnosing left ventricular diastolic dysfunction. The aim of the study was to validate the N-terminal propeptide of the brain natriuretic peptide (NT-proBNP) in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease.. In 64 patients, left ventricular diastolic dysfunction was classified using tissue Doppler imaging and serum levels of NT-proBNP were measured.. Left ventricular diastolic dysfunction was found in 25 of 31 (80.6%) patients with severe liver fibrosis/cirrhosis versus 2 of 8 (25.0%) patients with moderate and 6 of 25 (24.0%) patients with mild liver fibrosis (P<0.001). Mean NT-proBNP levels were 407.1+/-553.4 pg/ml in patients with severe fibrosis/cirrhosis as compared with 60.8+/-54.9 pg/ml and 55.4+/-41.4 pg/ml in patients with mild and moderate fibrosis (P=0.001). NT-proBNP was most accurate in predicting advanced left ventricular diastolic dysfunction with an area under the receiver-operating characteristic curve of 0.90 (95% confidence interval, 0.77-1.0; P<0.001). A cutoff value of greater than 290 pg/ml was highly predictive of advanced left ventricular diastolic dysfunction.. NT-proBNP is a useful marker in detecting advanced left ventricular diastolic dysfunction in patients with chronic liver disease. Patients with severe liver fibrosis/cirrhosis and NT-proBNP levels exceeding 290 pg/ml should undergo further cardiac evaluation.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Echocardiography, Doppler, Pulsed; Electrocardiography; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Reproducibility of Results; Severity of Illness Index; Ventricular Dysfunction, Left

Renal impairment, as measured by reduced glomerular filtration rate (GFR) and increased urinary albumin excretion (UAE), is prevalent in patients with chronic heart failure (CHF) and is associated with reduced survival. The prevalence of structural tubular damage in CHF is unknown. We investigated 90 CHF patients and 20 age and sex matched healthy controls, and determined estimated GFR, UAE, N terminal-pro brain natriuretic peptide (NT-proBNP) and urinary neutrophil gelatinase associated lipocalin (NGAL) as a marker for tubular damage. CHF patients had significantly lower averaged estimated GFR (64+/-17 vs 90+/-12 mL/min/1.73 m(2), P<0.0001), but higher NT-proBNP and UAE levels (both P<0.0001). Median urinary NGAL levels were markedly increased in CHF patients compared to controls (175 (70-346) vs 37 (6-58) microg/gCr, P<0.0001). Both serum creatinine (r=0.26, P=0.006) and eGFR (r=-0.29, P=0.002) were significantly associated with urinary NGAL levels as were NT-proBNP and UAE but to a lesser extent. In conclusion, renal impairment in CHF patients is not only characterised by decreased eGFR and increased UAE, but also by the presence of tubular damage, as measured by increased urinary NGAL concentrations.

Topics: Acute-Phase Proteins; Albumins; Case-Control Studies; Chronic Disease; Creatine; Disease Progression; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Diseases; Kidney Tubules; Lipocalin-2; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Proto-Oncogene Proteins; Stroke Volume; Ventricular Function, Left

We aimed to evaluate levels of amino-terminal pro-brain natriuretic peptid (NT-proBNP) in prediction of left ventricular ejection fraction (LVEF) in heart failure patients. Prospective study on 60 consecutive patients with symptoms and signs of heart failure was performed. Blood samples for NT-proBNP analysis was taken from all test subjects and echocardiography was also done in all of them. According to LVEF value, patients were divided into four groups; those with or=50%. NT-proBNP values correlated with LVEF value. Regression analysis was used to evaluate how well NT-proBNP values predict LVEF. We used Receiver Operating Characteristic Curve calculation to evaluate diagnostic performance of NT-proBNP in estimation of LVEF. Average value of NT-proBNP in test group was 3191.69+/-642.89 pg/ml (p<0.001). Average value of NT-proBNP decreased with higher LVEF categories with significant (p<0.001) and high negative correlation (r= -0,75). Stepwise multivariate linear regression analysis showed that logarithmic value of NT-proBNP was excellent predictor of LVEF value (p<0.05). Model equation based on regression analysis was LVEF=88.645-15.311 x log (NT-proBNP). Predictive model for LVEF yielded from regression analysis had sensitivities of 98% and 81%, specificities of 20% and 90%, positive predictive values of 86% and 78% and negative predictive values of 67% and 92% for predicting patients with LVEF<50% and LVEF<40%, respectively. There was negative linear correlation between NT-proBNP and LVEF. NT-proBNP was excellent predictor of LVEF value (p<0.05).

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Regression Analysis; Sensitivity and Specificity; Stroke Volume; Ventricular Function

To investigate the diagnostic and prognostic value of N-terminal probrain natriuretic peptide(NT-proBNP)and atrium natriuretic peptide(ANP)in chronic congestive heart failure.. One hundred and eighteen coronary heart disease patients were enrolled in the study. Among them 78 patients were accompanied by heart failure and 40 with no heart failure. Plasma NT-proBNP was determined with Elecsys Chemiluminescence Immunoassay method, and plasma ANP was determined with radioimmunoassay method.The results were compared with those of 40 healthy individuals. All patients were followed up accordingly.. Compared with patients with no heart failure and healthy individuals, the patients with heart failure had a higher plasma NT-proBNP and ANP contents(P<0.05). Cardiac function grade IV patients had a significantly higher plasma NT-proBNP than cardiac function grade II and III patients, and their plasma ANP level was significanthy higher than that of cardiac function grade III patients, but there was no significantly difference in ANP content between cardiac function grade IV and II.The diagnostic sensitivity of NT-proBNP and ANP was 91.25% and 73.46%, respectively. The diagnostic specificity of NT-proBNP and ANP was 90.25%, 80.33%, respectively. In the heart failure group, it was found that there was no significant difference in the plasma NT-proBNP and ANP between the deaths and surviving patients.. The diagnostic value of NT-proBNP in chronic heart failure is higher than that of ANP. According to our follow- up result, the plasma NT-proBNP and ANP can not be relied up on to predict short -term cardiogenic death in heart failure.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Radioimmunoassay

B-type natriuretic peptide (BNP), heart-type fatty acid-binding protein (H-FABP), and pentraxin 3 (PTX3) each predict adverse cardiac events in chronic heart failure (CHF) patients. For prognostic evaluation from different aspects, the utility of combined measurement of the 3 biomarkers in patients with CHF was examined in the present study.. Levels of BNP (associated with left ventricular dysfunction, positive if >200 pg/ml), H-FABP (marker of myocardial damage, positive if >4.1 ng/ml), and PTX3 (marker of inflammation, positive if >4.0 ng/ml) were measured in 164 consecutive CHF patients, and patients were prospectively followed with endpoints of cardiac death or rehospitalization. When patients were categorized on the basis of the number of elevated biomarkers, patients with 1, 2, and 3 elevated biomarkers had a 5.4-fold (not significant), 11.2-old (p<0.05), and 34.6-fold increase (p<0.01), respectively, in the risk of adverse cardiac events compared with those without elevated biomarkers. Kaplan-Meier analysis revealed that patients with 3 elevated biomarkers had a significantly higher cardiac event rate than patients with a lower number of elevated biomarkers.. The combination of these 3 biomarkers could reliably risk-stratify CHF patients for prediction of cardiac events.

Topics: Aged; Biomarkers; C-Reactive Protein; Chronic Disease; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Serum Amyloid P-Component

No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF).. To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF.. We measured haemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF.. During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273+/-276 vs. 472+/-433 pg/mL, p<0.0001), NT-proBNP (417+/-700 vs. 928+/-1093 pg/mL, p<0.0001) and NE (114+/-160 vs. 473+/-992 pg/mL, p<0.0001) were significantly higher in non-survivors than survivors. After adjustment for clinical variables associated with CHF including haemodynamics and neurohumoral factors, the transcardiac gradient of NE (p<0.0001) and plasma log NT-proBNP (p<0.0001) were independent prognostic predictors. Among 67 patients in whom 123I-metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE was correlated with the washout rate (r=0.398, p=0.0009) and was a superior predictor of mortality than MIBG parameters on stepwise multivariable Cox proportional hazards regression analyses.. The transcardiac increase in NE is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients.

Topics: Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Sympathetic Nervous System; Time Factors

In patients with chronic heart failure (CHF) QRS prolongation is a frequent finding and is related to increased morbidity and mortality. It is not clear if prolonged QRS in CHF of ischaemic origin (CAD) represents the same severity of the syndrome as in non-ischaemic (non-CAD) cardiomyopathy.. To assess the relationship between QRS duration and BNP levels, diastolic function and peak VO2 in patients with CAD CHF and non-CAD CHF.. In 70 patients with left ventricular ejection fraction (LVEF) <45% [35 with left bundle branch block (LBBB)] echocardiography, cardiopulmonary exercise test and standard ECG were performed as well as BNP level was measured.. Peak VO2 was significantly lower, BNP level higher in patients with LBBB than those without LBBB. In the non-CAD CHF peak VO2 was significantly lower, whereas BNP levels and restrictive filling pattern prevalence higher in the group with LBBB than without LBBB, which was not seen in the CAD CHF group. A significant correlation between peak VO2 and BNP levels (r=-0.31; p=0.02), QRS duration (r=-0.27; p=0.02), and diastolic function parameter - DTE (r=0.28; p=0.02) was found. Peak VO2 was significantly lower in the CAD CHF than in non-CAD CHF. In multivariate regression analysis, LVEF (r=-0.32; p=0.012) and LVEDD (r=0.30; p=0.015) were independently associated with QRS duration.. In patients with CHF, QRS duration is independently related to LVEF and LVEDD. It seems that prolonged QRS may be a better predictor of more advanced CHF in patients with non-ischaemic rather than ischaemic cardiomyopathy.

Topics: Aged; Bundle-Branch Block; Chronic Disease; Coronary Disease; Diastole; Echocardiography; Electrocardiography; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume

Heart rate turbulence (HRT) is modulated by the baroreceptor reflex, and it has been suggested that it could be used as a measure of autonomic dysfunction. Impaired HRT has a significant prognostic value in patients after myocardial infarction. The usefulness of HRT parameters in CHF patients has not yet been well established.. To assess the relationship between HRT parameters, clinical course of CHF and selected biochemical markers with respect to their prognostic value in CHF patients.. A 64 of 100 consecutive CHF patients, in whom it was possible to calculate HRT, were divided into four groups according to NYHA class. Uric acid (UA) and brain natriuretic peptide (BNP) concentrations were measured. Heart rate turbulence was analysed from 24-hour Holter ECG and characterised by two parameters: turbulence onset (TO) and turbulence slope (TS). The results of 20 healthy persons served as a control group. Follow-up examinations were performed after 6 and 12 months.. In patients with CHF both HRT parameters (TO and TS) were significantly impaired in comparison to TO and TS in healthy subjects. A negative correlation between these parameters was found. A strong positive correlation between TO and NYHA class and a significant negative correlation between TS and BNP and UA concentrations were observed. There were 11 deaths during one-year follow-up. Patients who died due to CHF had significantly lower TS and higher TO values in comparison to survivors.. Heart rate turbulence is impaired in CHF patients. HRT parameters show a significant correlation with some clinical factors: NYHA class, BNP and UA concentrations. Both HRT parameters, TO and TS, seem to be significant prognostic markers in patients with CHF.

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Case-Control Studies; Causality; Chronic Disease; Comorbidity; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pressoreceptors; Prognosis; Survival Analysis; Uric Acid

Topics: Biomarkers; CA-19-9 Antigen; Chronic Disease; Female; Heart Failure; Humans; Hypertrophy, Right Ventricular; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Ultrasonography

The Myocardial performance index (MPI) is an echocardiographic index of combined systolic and diastolic function, calculated as isovolumetric relaxation time plus isovolumetric contraction time divided by ejection time. The aim of this study was to define the correlation of the MPI with plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters in patients with chronic mitral regurgitation (MR).. About 33 patients with at least moderate MR of organic etiology were enrolled to the study. All patients undergone complete 2D and Doppler echocardiography. Plasma BNP levels were studied.. BNP levels in NYHA classes I-III were 9.3 +/- 2.2 pg/ml, 61.3 +/- 12.2 pg/ml, and 199.6 +/- 55.2 pg/ml, respectively (I vs. II P < 0.001, I vs. III P < 0.001 and II vs. III P = 0.004). Myocardial performance index were 0.42 +/- 0.02, 0.49 +/- 0.02, and 0.52 +/- 0.03 in MR patients with NYHA I-III, respectively. MPI was significantly higher in patients with NYHA class III compared to NYHA I (P = 0.001) and NYHA II (P = 0.005). There were no correlations between MPI and left atrial diameter, MR jet area, MR index and systolic pulmonary artery pressure whereas left ventricle (LV) end-systolic volume (r = 0.38), LV end-diastolic volume (LVDV) (r = 0.40), LV ejection fraction (r = -0.59), NYHA class (r = 0.51) and plasma BNP levels (r = 0.67) were strongly correlated. Only independent variable affecting MPI was plasma BNP level (odds ratio [CI]: 2.18[0.002-0.098], P = 0.041).. MPI is a powerful index in assessing the severity of left ventricular function and symptom severity in patients with MR. Plasma BNP is an independent predictor of MPI where both parameters assess combined systolic and diastolic LV function, effectively.

Topics: Analysis of Variance; Biomarkers; Chronic Disease; Comorbidity; Diastole; Echocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Contraction; Natriuretic Peptide, Brain; Statistics, Nonparametric; Systole

Recent studies have shown that obesity is an independent predictor of lower N-terminal pro-BNP (NT-proBNP) levels and raised concerns about the validity of this biomarker in obese subjects. We evaluated the influence of obesity (body mass index>or=30 kg/m(2)) on the correlation between exercise capacity and serum NT-proBNP levels in 100 chronic heart failure (CHF) patients referred for cardiopulmonary exercise testing. Circulating NT-proBNP levels correlated well with lean body mass-adjusted peak oxygen consumption (VO(2)) in the entire cohort (R=-0.72, p<0.001) and in the obese (R=-0.71, p<0.001) and non-obese (R=-0.72, p<0.001) subgroups. There was no significant difference between the correlation coefficients of the two subgroups (p=0.934). In conclusion NT-proBNP levels predict exercise capacity in CHF patients irrespective of the presence of obesity.

Topics: Aged; Chronic Disease; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

Both, severe hypo- or hyperthyroidism may alter hemodynamic parameters. The aim of our study was to ascertain, whether also distinct changes within normal range of free thyroxine (fT4) would be associated with an impairment of left ventricle function in patients with chronic heart failure. Hundred-forty-eight patients (m121, f27, mean age 63.8 +/- 1.14 years) with chronic heart failure, fT4 levels within the normal range (9-22 pmol/l) and without thyrostatics or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP). Patients with fT4 in the range 11.9-14.6 pmol/l [optimal, second-third quintile] had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 [low-normal, bottom quintile](1236 +/- 223.6 pg/ml; p<0.03) and those with fT4 over 14.6 pmol/l [high-normal, top two quintiles] (1192 +/- 114.9 pg/ml; p<0.0002). These differences remain significant, also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were also found in BNP, but only when optimal and high-normal fT4 ranges were compared. In conclusion, the severity of heart failure seems to be also influenced by only mild deviations of fT4 concentrations from optimal levels.

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotensin; Odds Ratio; Thyroxine; Ventricular Function, Left

To determine whether plasma levels of B-type natriuretic peptide (BNP) predict left ventricular (LV) dysfunction on exercise echocardiography in patients with moderate to severe aortic regurgitation (AR).. Case-control study.. Outpatient cardiology departments.. 39 asymptomatic or mildly symptomatic patients with chronic moderate to severe AR and a normal LV ejection fraction (>50%), and 10 normal controls.. Plasma level of BNP and echocardiographic measures of LV function at rest and immediately after treadmill exercise.. LV end systolic volume index (LVESVI) was significantly increased in AR patients with normal BNP (0.05 for all). However, there were modest but statistically significant associations between the plasma level of BNP and severity of AR indicated by a greater AR:LV outflow tract width ratio (r = 0.37, p = 0.02) and lower diastolic blood pressure (r = -0.44, p = 0.004). Increased BNP was also associated with a greater LVESVI (r = 0.33, p = 0.04) and lower LV longitudinal strain rate (r = -0.037, 0.02) on echocardiography after exercise.. In moderate to severe AR compensatory LV remodelling can occur with no increase in plasma BNP. Increased BNP is associated with more severe regurgitation and changes consistent with early LV dysfunction on exercise echocardiography.

Topics: Adolescent; Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Case-Control Studies; Chronic Disease; Echocardiography, Stress; Exercise Test; Humans; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

To investigate the relationship between the plasma B-type natriuretic peptide (BNP) level and the occurrence of atrial fibrillation (AF) in nonobstructive hypertrophic cardiomyopathy (HCM) patients.. Patients (n=97) were classified into chronic AF (CAF; n=14), paroxysmal AF (PAF; n=18) and normal sinus rhythm (NSR; n=65) groups. The plasma BNP values were analyzed with logarithmic transformation.. The PAF group showed significantly higher plasma BNP levels than the NSR group [mean (range; -l SD and +1 SD); 248.3 (143.5, 429.5) vs. 78.2 (27.9, 218.8 ng/L), p<0.0001]. The CAF group also showed significantly higher plasma BNP levels than the NSR group [291.1 (161.4, 524.8 ng/L), p<0.0001]. Multivariate analysis with other clinical factors selected association of PAF as one of the factors that increased the plasma BNP level.. The present study indicated that plasma BNP level is clinically useful for identification of nonobstructive HCM patients who have a risk of PAF.

Topics: Aged; Atrial Fibrillation; Biomarkers; Cardiomyopathy, Hypertrophic; Chronic Disease; Echocardiography, Doppler; Female; Fluoroimmunoassay; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Risk Assessment; Tachycardia, Paroxysmal

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR.. This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001).. NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

Topics: Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Severity of Illness Index; Stroke Volume

Circulating levels of atrial natriuretic peptide and brain natriuretic peptide (BNP) are elevated in patients with cyanotic congenital heart disease and associated with the severity of ventricular dysfunction. We evaluated the effect of chronic hypoxemia on left ventricle pro-atrial natriuretic peptide and pro-BNP, the cytoplasmic precursors of the plasma hormones.. Forty newborn piglets were randomized to placement of a pulmonary artery to left atrium shunt to create hypoxemia or sham thoracotomy. Animals were studied at 1 or 2 weeks after the procedure (four groups, n = 10 per group). Arterial oxygen tension and hematocrit were obtained. Left ventricular shortening fraction was measured by echocardiography. Left ventricular tissue was harvested and cytoplasm was extracted. Pro-BNP levels were determined by Western blot analysis. Pro-atrial natriuretic peptide levels were determined using enzyme-linked immunosorbent assay.. Significant differences among treatment groups were observed for arterial oxygen tension (p < 0.001) and hematocrit (p < 0.001). Pairwise comparisons indicated lower arterial oxygen tension and higher hematocrit for hypoxemic piglets compared with control piglets at 1 and 2 weeks. Left ventricular shortening fraction was not decreased in the hypoxemic animals at any time (p = 0.638). Left ventricular pro-atrial natriuretic peptide decreased in hypoxemic piglets (p = 0.029), whereas left ventricular pro-BNP increased in hypoxemic piglets at 2 weeks (p = 0.002).. Chronic hypoxemia alone, even in the absence of cardiac dysfunction, is sufficient to increase ventricular levels of pro-BNP. This finding may have implications for the interpretation of BNP levels in the clinical management of patients with cyanotic congenital heart disease.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Heart Defects, Congenital; Hypoxia; Natriuretic Peptide, Brain; Probability; Prognosis; Protein Precursors; Random Allocation; Sensitivity and Specificity; Swine

To examine the efficacy and safety of torasemide in children with chronic heart failure (HF).. 102 children with chronic HF who had received oral torasemide were analysed. Of these, 62 (de novo group) were newly diagnosed as having HF and were given torasemide as a diuretic. The remaining 40 (replacement group) had been given furosemide for >3 months before the study, and furosemide was then replaced with torasemide. Clinical signs and symptoms of HF (assessed as the HF index), humoral factors and serum potassium concentrations before torasemide treatment were compared with those obtained 3-4 weeks after torasemide treatment. Patients were also monitored for adverse effects.. In the de novo group, torasemide significantly improved the HF index with concomitant improvement in plasma brain natriuretic peptide concentration (median (interquartile range) 52 (51) vs 43 (49) pg/ml). In a randomly selected group of 25 de novo patients with ventricular septal defect, echocardiography showed that torasemide significantly improved left ventricular geometry and function. In the replacement group, brain natriuretic peptide concentrations were also significantly decreased from 50 (104) to 45 (71) pg/ml after substitution of torasemide, but the HF index showed only a tendency for improvement (p = 0.07). Torasemide also had a potassium-sparing effect (de novo group, no change in potassium concentration; replacement group, significant increase from 4.2 (0.5) to 4.3 (0.5) mEq/l), and caused a significant rise in serum aldosterone concentration, consistent with the anti-aldosterone effect of this drug. Serum concentrations of sodium and uric acid had not changed after torasemide treatment, and there were no serious adverse events that necessitated drug withdrawal.. Torasemide can be safely used, and appears to be effective for treatment of HF in children. Future clinical trials are warranted to verify the present results.

Topics: Child, Preschool; Chronic Disease; Diuretics; Female; Heart Failure; Humans; Infant; Infant, Newborn; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Prospective Studies; Sulfonamides; Survival Rate; Torsemide; Treatment Outcome

Inflammation plays a pathogenic role in the development of chronic heart failure (CHF). Increasing evidence shows that CD40-CD40 ligand (CD40L) interaction plays a pathogenic role in inflammatory disorders. We assessed whether CD40 ligand expression was abnormal in patients with CHF.. Twenty normal controls and 86 patients with CHF were investigated. The expression of CD40L on platelets was analyzed by indirect-immunofluorescence flow cytometry, and the soluble CD40L (sCD40L) level was determined by a commercially available enzyme-linked immunosorbent assay (ELISA). B type natriuretic peptide (BNP) was measured by radioimmunoassay.. All patients with CHF showed a significant increased expression of CD40L (32.3+/-13.9 MFI) on platelets and sCD40L levels (20.5+/-8.6 microg/l) compared with controls(p<0.0001). CD40L expression on platelets and sCD40L levels positively correlated with New York Heart Association (NYHA) functional class, left ventricular ejection fraction and BNP levels in CHF.. Patients with CHF showed increased expression of CD40L system, which may create a pathogenic role in the development and progression of CHF.

Topics: Aged; Blood Platelets; CD40 Ligand; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Platelet Activation; Stroke Volume

Topics: Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

The role of the amino-terminal fragment of probrain natriuretic peptide (NT-proBNP) in monitoring the clinical status of outpatients with chronic heart failure has not yet been fully established. Fifty-nine patients with chronic heart failure were followed up at an outpatient clinic. The serum NT-proBNP level was measured and clinical status was assessed according to New York Heart Association (NYHA) functional class and Framingham clinical criteria. A positive correlation was found between the NT-proBNP level, NYHA functional class and Framingham score (P< .001). Patients who presented with a Framingham score > 2 were more likely to be readmitted to hospital (31.8% vs. 0%; P< .001), to visit an emergency department (36.4% vs. 5.4%; P=.002), or to die (13.6% vs. 0%; P=.021). The NT-proBNP level was higher in patients who needed to be readmitted to hospital (P=.004) and in those who attended an emergency department for decompensation (P=.002).

Topics: Aged; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Severity of Illness Index

In chronic heart failure, atrial and brain natriuretic peptide expression is increased and serves as a clinical marker of cardiac hypertrophy. Chromogranin A is also up-regulated during chronic heart failure and associated with disease severity and prognosis. Significant decrease of both natriuretic peptide and hypertrophy after left ventricular assist device (LVAD) treatment was reported. This study investigated whether chromogranin A and neural cell adhesion molecule (NCAM)/CD56 are associated with cardiac hypertrophy and regulated by LVAD.. Expression of atrial and brain natriuretic peptide, chromogranin A, and NCAM/CD56 were investigated by immunohistochemistry and morphometrically quantified in 33 paired myocardial samples before and after LVAD. In a different set of patients, chromogranin A was evaluated in the plasma. Cardiomyocyte colocalization of brain natriuretic peptide and chromogranin A was visualized by immunofluorescence doublestaining.. Natriuretic peptide and chromogranin A protein expression is significantly decreased after LVAD (p < 0.05). NCAM/CD56 expression remains unaltered by unloading. In contrast with natriuretic peptide, chromogranin A and NCAM/CD56 expression is not correlated with cardiomyocyte diameters. Although increased compared with controls, no significant differences for chromogranin A plasma levels were found before and after LVAD. Sarcoplasmic colocalization of chromogranin A and brain natriuretic peptide is considerably decreased after LVAD.. Neither chromogranin A nor CD56 is associated with cardiac hypertrophy. Chromogranin A is significantly decreased by ventricular support. Sarcoplasmic colocalization of brain natriuretic peptide and chromogranin A is diminished after unloading. However, owing to its low expression, the negative regulation of chromogranin A is not reflected by plasma levels and thus does not appear to be an appropriate biomarker of reverse cardiac remodeling after unloading.

Topics: Adolescent; Adult; CD56 Antigen; Child; Child, Preschool; Chromogranin A; Chronic Disease; Down-Regulation; Female; Heart Failure; Heart-Assist Devices; Humans; Hypertrophy; Male; Middle Aged; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Neural Cell Adhesion Molecules; Sarcoplasmic Reticulum; Tissue Distribution; Ventricular Remodeling

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Drug Therapy, Combination; Enalapril; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Risk Assessment; Time Factors; Treatment Outcome

Topics: Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Heart Valve Prosthesis Implantation; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Predictive Value of Tests; Preoperative Care; Severity of Illness Index; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

We evaluated the role of clinical, BNP and echocardiographic left ventricular (LV) indices in predicting the development of acute heart failure (HF) following beta-blocker initiation and uptitration in 50 stable CHF patients with LVEF < 40% and creatininemia < 250 micromol/l. Use of NYHA class alone predicted the development of acute HF decompensation in only 56% and the absence of this event in 93% of patients. Use of echocardiographic indices (systolic PAP < 40 mmHg or E/A ratio < 1.4 or EDT > 145 ms) predicted the absence of acute HF decompensation in 100% of patients. Use of NYHA > 3 combined with BNP > 398 pg/ml or with echocardiographic indices (i.e. systolic PAP > 40 mmHg or E/A > 1.4 or EDT < 145 ms) predicted the development of acute HF decompensation in 100% of patients. In conclusion use of BNP and echocardiographic LV filling pressure indices in combination with NYHA class may predict beta-blocker tolerance more accurately than clinical indices alone in patients with LV systolic dysfunction (LVEF < 40%).

Topics: Acute Disease; Adrenergic beta-Antagonists; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Systole; Ultrasonography; Ventricular Dysfunction, Left

Acute changes of the AV-delay in CRT patients have a significant impact on hemodynamics. However, the chronic functional effects of AV-delay optimization have not been systematically examined despite of their potential role for chronic functional improvement.. Therefore, in this study we investigated whether optimization of AV-delay in CRT patients as assessed by echocardiographic measurement of the velocity time integral of the left ventricular outflow tract (LVOT-VTI) chronically changes (1) echocardiographic parameters of systolic and diastolic left ventricular function, (2) walking distance in the 6-min walk test, (3) levels of NT-proBNP and (4) quality of life as assessed by a standard questionnaire. 33 patients underwent optimization of AV-delay 31+/-8 weeks after initiation of CRT. Follow up (FU) was conducted 43+/-5 days later.. E/Ea, the ratio of peak E-wave of mitral inflow and of TDI of the mitral annulus, significantly decreased immediately post-optimization (11+/-1 vs. 14+/-1 at baseline, p<0.05) and further decreased at FU (8+/-1, p<0.05 vs. immediately post-optimization) indicating improvement of diastolic function, while traditional parameters of diastolic function derived from pulse wave Doppler remained unchanged. There was a slight increase of LV-ejection fraction as assessed by echocardiography acutely after optimization (baseline: 25+/-2%, optimized: 28+/-1%, p<0.05), while LV-ejection fraction at FU did not differ from baseline. 6-min walk test improved from 449+/-17 m (baseline) to 475+/-17 m at FU (p<0.05). During this period NT-proBNP significantly decreased from 3193+/-765 ng/l to 2593+/-675 ng/l (p<0.05). Quality of life was unchanged at FU.. This study demonstrates for the first time chronic functional improvement due to AV-delay optimization in patients with CRT.

Topics: Acute Disease; Aged; Biomarkers; Cardiac Pacing, Artificial; Chronic Disease; Echocardiography, Doppler, Pulsed; Electrocardiography; Exercise Test; Exercise Tolerance; Female; Heart Conduction System; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pacemaker, Artificial; Peptide Fragments; Probability; Quality of Life; Stroke Volume; Treatment Outcome

Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF.. Fourteen patients (9 men, 5 women, mean age 68+/-13 years) undergoing biventricular pace-maker/ICD implantation were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP levels. The evaluation was repeated 48 h and 9+/-2 months after device implantation to assess the acute and chronic effects of CRT on apelin and NT-proBNP levels. Eight healthy age- and sex-matched subjects served as controls. In CHF patients, baseline apelin levels were reduced and NT-proBNP increased compared to control subjects (apelin: 0.47+/-0.2 vs. 0.97+/-0.3 ng/mL, p<0.001; NT-proBNP: 2007+/-114 vs. 229+/-72 pmol/L, p<0.001). Short-term evaluation did not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9+/-2 months follow-up, CRT responders showed left ventricular reverse remodelling and an increase in ejection fraction, together with a significant increase in plasma apelin levels (0.99+/-0.1 vs. 0.47+/-0.2 ng/mL, p<0.001) and decrease in NT-proBNP (938+/-591 vs. 2007+/-114 pmol/L, p<0.05).. Long-term CRT increases plasma levels of the endogenous inotrope apelin in patients with CHF.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Apelin; Biomarkers; Cardiac Pacing, Artificial; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Treatment Outcome

Brain natriuretic peptides are elevated in patients with systolic heart failure (HF) as well as in patients with atrial fibrillation (AF) and normal left ventricular ejection fraction (LVEF) and are strong predictors of death in HF patients. The aim of our study was to examine the levels of N-terminal pro brain natriuretic peptide (NT-proBNP) in patients with HF and AF versus HF and sinus rhythm (SR) and if NT-proBNP has prognostic influence in patients with AF.. We included 245 patients (72% men, 70 years) with HF referred to a HF clinic. NT-proBNP was measured at referral (baseline).. At baseline, 26% had AF and at follow-up 35% of the surviving patients. Patients with AF were older than patients with SR (p=0.009), but LVEF and NYHA distribution were similar. Median NT-proBNP levels were higher: 2528 vs. 899 pg/ml (p<0.001). NT-proBNP was significantly correlated with AF at baseline (p<0.001), age (p=0.001), P-creatinine (p<0.001) and reduced LVEF (p=0.002). NT-proBNP was an independent predictor of death in patients with AF, adjusted HR 4.0 (95% CI 1.6-10.2) (p=0.003).. NT-proBNP levels are higher in HF patients with AF than in HF patients with SR and has prognostic value despite the presence of AF.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

Several studies have reported that plasma brain natriuretic peptide (BNP) levels are increased in patients with chronic atrial fibrillation (AF). The objective of this study was to assess the factors influencing plasma BNP levels in patients with chronic AF and preserved left ventricular (LV) systolic function.. Transthoracic echocardiography was performed in 104 patients (48 men, 56 women; mean age, 63.9+/-10.7 years) with chronic AF. At the same time, plasma BNP levels were measured with a Triage kit (Biosite, San Diego, CA).. Women, long duration of AF, and hypertension were more prevalent in the highest quartile group of BNP levels than in the lowest quartile of BNP. Significant correlations were observed between plasma BNP levels and the following: mitral E velocity (r=0.343), mitral annular E' velocity (r=-0.402), ratio of mitral E velocity and mitral annular E' velocity (r=0.487), left atrial(LA) size (r=0.653), LA volume index (r=0.775), right atrial (RA) volume index (r=0.563), maximal velocity (V(max)) of mitral regurgitation (MR) (r=0.448), tricuspid regurgitation (TR) V(max) (r=0.532) and LV mass index (r=0.581). In stepwise multiple linear regression analysis, LA volume index (beta=0.326, p<0.001), LV mass index (beta=0.395, p<0.001) and duration of AF (beta=0.492, p<0.001) independently predicted plasma BNP levels in the study subjects. The patients with increased LA volume index exhibited a longer duration of AF, larger RA volume index and LV mass index, higher MR V(max), TR V(max) and plasma BNP level.. LA volume index, LV mass index and duration of AF are independent predictors of plasma BNP levels in patients with chronic AF and preserved LV systolic function.

Topics: Atrial Fibrillation; Biomarkers; Chronic Disease; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Sex Factors; Ultrasonography; Ventricular Function, Left

We sought to compare the additive value of right ventricular (RV) function assessed by longitudinal systolic strain (epsilon% - ROI: 9.2 at 10.8 mm) with cardiopulmonary exercise testing (CPET) or brain natriuretic peptide (BNP) in patients with heart failure (HF).. We studied 19-patients (age = 56 +/- 8 years) in New York Heart Association HF class III-IV, who underwent standard and tissue Doppler echocardiography, CPET and BNP measurements on the same day. RV function was assessed by systolic strain (epsilon, %, ROI: 9.2-10.8 mm) in the mid-segment. Clinical outcomes were examined at 6 months.. epsilon (-19.9+/-6.8%) was correlated with BNP (R = 0.52, P = 0.02), slope VE/VCO(2) (R = -0.65, P = 0.003), peak VO(2) (R = 0.46, P = 0.04) and the maximal workload (Watts) developed during CPET (R = 0.54, P=0.02). During follow-up, 1-patient died, 1-underwent heart transplantation, and 4 were re-hospitalized for worsening HF. Patients with major adverse cardiac events (MACE) had a significantly higher mean BNP concentration (852.8 ng/mL +/- 1114.3 vs. 201.4+ /- 293.8, P = 0.03), higher VE/VCO(2) (41.3 +/- 3.6 vs. 35.0 +/- 4.8 P < 0.001) and lower epsilon (-13.9 +/- 4.9 vs. -22.2+ /- 5.8, P < 0.001) than patients who remained MACE-free. By multivariate analysis, ST was the only predictor of MACE.. In HF-patients presenting, RV-function assessed by systolic epsilon was reliable, easily measurable and a stronger prognosticator than CPET or BNP.

Topics: Chronic Disease; Echocardiography, Doppler; Exercise Test; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Regression Analysis; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Right

Here, the aim is to assess long-term clinical variation (CV) of N-terminal pro-brain natriuretic peptide (NT-proBNP) in stable chronic heart failure (CHF) patients. The proposed use of NT-proBNP for monitoring of CHF patients will require accurate information about long-term CV of the peptide.. Medication, biochemical variables, and NYHA class were recorded at 1-year and 2-year follow-up in patients treated in our heart failure clinic. Only patients without changes in medication and the NYHA class who were not hospitalized or died in the period from first follow-up to 12 months after the second follow-up were included. A total of 78 patients fulfilled the criteria, and year-to-year CV was calculated to 30% (median) (range: 0-111%) (% changes range: -87 to 397%). Log transformation of NT-proBNP (skewed to the right) reduced the year-to-year CV to 4.7% (range: 0-22%) (% changes range: -18 to 38%).. Long-term CV of plasma concentrations of NT-proBNP in stable CHF patients is 30%, but the variation is substantial. Therefore, high long-term CV of NT-proBNP does not necessarily carry prognostic significance within the subsequent 12 months. Plasma concentrations of NT-proBNP followed a lognormal distribution, and the low CV of log(NT-proBNP) indicate that NT-proBNP levels are constant during stable conditions.

Topics: Aged; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors

Early diagnosis and treatment are pivotal for patients with acute aortic dissection (AAD). D-dimer is a rule-out diagnostic test for pulmonary embolism but there is evidence that it may also be applicable to AAD. We evaluated plasma D-dimer, white cell blood count (WBC), C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (BNP) in 18 consecutive patients with established AAD, 21 consecutive patients with dilated ascending aortas scheduled for elective surgery and 8 normal subjects. Patients with AAD had significantly higher elevated D-dimer, compared to chronic aneurysms and normal controls (p<0.0001). D-dimer level higher than 700 ng/ml had a sensitivity of 94% and specificity of 59% for diagnosis of AAD. The WBC count was also significantly increased compared to the other groups (p<0.01). CRP and BNP values were significantly higher compared to normal controls but these parameters did not distinguish between AAD and chronic aneurysms. D-dimer can be used as a 'rule-out' test in patients with suspected AAD and seems useful in the discrimination between AAD and chronic uncomplicated aneurysms, unlike CRP and BNP plasma levels.

Topics: Acute Disease; Acute-Phase Reaction; Adolescent; Adult; Aged; Aortic Aneurysm; Aortic Dissection; C-Reactive Protein; Chronic Disease; Female; Fibrin Fibrinogen Degradation Products; Humans; Leukocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sensitivity and Specificity

In chronic thromboembolic pulmonary hypertension, objective data to assess the functional outcome after pulmonary endarterectomy are lacking. We studied the 6-minute walk distance in relation to the clinical and hemodynamic severity of disease, and assessed the effect of pulmonary endarterectomy on the 6-minute walk distance.. A total of 50 consecutive patients with chronic thromboembolic pulmonary hypertension were studied. Subsequently, pulmonary endarterectomy was performed in 42 patients, 35 of whom underwent a 6-minute walk distance 1 year after surgery.. The mean +/- standard error of the mean 6-minute walk distance was 391 +/- 19 m. The 6-minute walk distance decreased in proportion to New York Heart Association functional class and correlated (all P < .0001) with mean pulmonary artery pressure (r = -0.62), cardiac output (r = 0.76), total pulmonary resistance (r = -0.75), mixed venous oxygen saturation (r = 0.77), and brain natriuretic peptide (r = -0.65). One year after pulmonary endarterectomy, the 6-minute walk distance increased from 417 +/- 19 m to 517 +/- 16 m (P < .0001). The change from baseline in 6-minute walk distance correlated with the changes after 1 year in New York Heart Association functional class (P < .01) and brain natriuretic peptide (r = 0.57, P < .002), and with the observed hemodynamic changes directly after pulmonary endarterectomy (change in mean pulmonary artery pressure: r = 0.52; change in cardiac output: r = 0.70; change in total pulmonary resistance r = 0.70; all P < .001). In patients with residual pulmonary hypertension after pulmonary endarterectomy, the 6-minute walk distance was significantly lower than in hemodynamically normalized patients. However, the absolute increase in the 6-minute walk distance was higher in patients with residual pulmonary hypertension (137 +/- 26 m and 82 +/- 20 m, respectively; P = .03).. The 6-minute walk distance was demonstrated to reflect the clinical and hemodynamic severity of disease in patients with chronic thromboembolic pulmonary hypertension. One year after pulmonary endarterectomy, the 6-minute walk distance had increased significantly, and the change in the 6-minute walk distance correlated with the observed clinical and hemodynamic improvement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Cohort Studies; Endarterectomy; Exercise Test; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Prospective Studies; Pulmonary Circulation; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Rate; Thromboembolism; Time Factors; Treatment Outcome; Vascular Patency; Walking

An increase in circulating B-type natriuretic peptide (BNP) is associated with a poor outcome in patients with acute heart failure. The primary aim of this study was to investigate the prognostic value of BNP levels in patients with chronic and advanced heart failure.. Fifty patients with New York Heart Association functional classes III and IV were enrolled in the study. Their blood BNP levels at admission were measured and patients were on follow up for 12 +/- 2 months.. There was no significant correlation between BNP levels on admission and left ventricular ejection fraction (r = 0.12, P > 0.05). Twelve patients (24%) died during the follow up. BNP levels were lower in patients who died (501 +/- 72 vs 877 +/- 89 ng/L, P < 0.01). The logistic stepwise regression analysis showed that lower BNP level (<520 ng/L) on admission was an independent predictor of cardiovascular mortality in these patients (odds ratio 1.21, 95% confidence interval 1.06-2.32, P < 0.01).. We conclude that patients with chronic and advanced heart failure have a lower circulating BNP level than those who survive. The paradoxically low BNP level is an adverse prognostic marker in advanced heart failure.

Topics: Adult; Aged; Cardiac Output, Low; Chronic Disease; Disease Progression; Echocardiography, Doppler, Pulsed; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Stroke Volume

Renal impairment (RI) has been shown to be one major risk factor in a number of diseases and is associated with a dismal clinical outcome. However, the influence of milder degrees of renal disease is less well defined, particularly not in patients with malignant diseases.. We analyzed 167 patients with solid tumors and hematological malignancies. Besides disease-specific parameters, serum creatinine, cystatin C and the estimated glomerular filtration rate (eGFR) ['modification of diet in renal disease' equation (MDRD)/Cockcroft-Gault (CG)] were determined. Patients were compared within eGFR, creatinine and cystatin C groups.. The median MDRD, CG, creatinine and cystatin C levels of all patients were 88 ml/min/1.73 m2, 89 ml/min, 1 mg/dl and 0.9 mg/l, respectively. Patients with chronic kidney disease stage 2 still showed normal creatinine and cystatin levels of 1 mg/dl and 1.1 mg/l, respectively, although mild RI was frequent. Those cancer patients with decreased eGFR (MDRD) (<60 ml/min/1.73 m2) had increased odds ratios (ORs) to have more concurrent diagnoses [OR 3.4; 95% confidence interval (CI) 1.5-8.1], a body mass index >24 kg/m2 (OR 2.1; 95% CI 1.0-4.5) and an elevated (> 245 pg/ml) pro-brain natriuretic peptide level (proBNP) (OR 9.2; 95% CI 3.0-28.3).. These observations suggest that grouping cancer patients according to renal function, especially eGFR, may be one way to determine specific risk groups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Chronic Disease; Creatinine; Cystatin C; Cystatins; Female; Glomerular Filtration Rate; Hematologic Neoplasms; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Neoplasms; Protein Precursors

Growth hormone (GH) resistance with a reduction of insulin-like growth factor-I (IGF-I) serum concentrations seems to be implicated in the catabolic process associated with chronic heart failure (CHF). However, data concerning the prognostic value of these alterations in CHF patients without cachexia are scant. In this study, we aimed to determine in CHF patients the prognostic value of IGF-I/GH ratio and its relationships with N-terminal brain natriuretic peptide (NT-proBNP), a known marker of prognosis in these patients.. We enrolled 82 non-cachectic patients, mean age 61+/-13 years, with ejection fraction <40% and predischarge New York Heart Association (NYHA) functional classes II-IV. All patients underwent clinical examination, two-dimensional echocardiography and NT-proBNP, GH and IGF-I measurement with log IGF-I/GH ratio calculation. Mortality and clinical status was documented at follow-up (18.4+/-8.1 months).. During follow-up 17 patients died of cardiac causes. Non-survivors were at baseline in higher NYHA class (P<0.05) and showed higher values of NT-proBNP (P<0.001) than survivors; differently IGF-I, and log IGF-I/GH ratio were lower (P<0.05). At Cox multivariate analysis, NT-proBNP (P<0.001) and IGF-I/GH ratio (P<0.05) were independent predictors of death.. High NT-proBNP levels and low IGH-I/GH ratio may be useful to stratify CHF patients at higher risk of cardiac death.

Topics: Adult; Aged; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Insulin-Like Growth Factor I; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Regression Analysis; Risk Factors; Wasting Syndrome

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia.. This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays.. NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI.. High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Placental Circulation; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Third; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

To evaluate whether plasma high molecular weight (HMW) adiponectin provides prognostic information in addition to that obtained from clinical, haemodynamic, and biochemical variables previously known to be associated with a high mortality in chronic heart failure (CHF) patients.. We measured the plasma levels of total and HMW adiponectin, atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-terminal-proBNP (NT-proBNP), and haemodynamic parameters in 449 consecutive CHF patients. Based on body mass index (BMI), patients were classified into three groups: low (<21 kg/m(2), n = 133), normal (21-25 kg/m(2), n = 205), and high (>25 kg/m(2), n = 111). After adjustment for clinical variables associated with CHF including haemodynamics, plasma total adiponectin level was an independent prognostic predictor but HMW adiponectin was not in the overall patient group. On subgroup analyses, in patients with abnormal BMI, plasma total adiponectin level was not an independent prognostic predictor, but in patients with normal BMI, plasma levels of log NT-proBNP (P = 0.017) and log total adiponectin (P = 0.003) were independent prognostic predictors.. These findings indicate that total adiponectin is more useful for assessing mortality risk than HMW adiponectin and a high plasma total adiponectin is an independent prognostic predictor especially in CHF patients with normal BMI.

Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Molecular Weight; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Regression Analysis; Risk Factors; Survival Analysis

Natriuretic peptides are considered as reliable indicators of left-heart failure (HF) and are useful for differential diagnosis of dyspnoea.. We evaluated the clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic hypercapnic respiratory failure (CHRF).. In 60 patients with CHRF, plasma concentrations of NT-proBNP were assessed at baseline and after treatment including non-invasive ventilation (NIV). The relationship of NT-proBNP to disease severity and its predictive value for survival were evaluated up to 4 years.. NT-proBNP levels were markedly elevated in patients with CHRF (n=60; geometric mean (SD) 546.4 (4.9) pg/mL; p<0.001) compared to healthy controls (n=182; 49.0 (2.2) pg/mL). After excluding patients with concomitant HF or renal impairment, levels were still increased (n=43; 393.2 (3.8) pg/mL; p<0.001). According to multivariate regression, hypoxia and exacerbation independently determined NT-proBNP levels (p<0.05 each). After initiation of NIV, blood gases and lung function improved and NT-proBNP decreased (-31.3 (0.3)%; p<0.001). During 22.5 (2.2) months follow-up, NT-proBNP was not significantly associated with survival in the total population, however, the subgroup of patients with levels >722 pg/mL (67th percentile) and no adherence to NIV displayed poor prognosis (hazard ratio=0.21; 95%-CI=0.022-0.580; p=0.0091).. NT-proBNP was highly elevated in patients with CHRF and correlated with the degree of respiratory impairment and exacerbation. Correspondingly, treatment including NIV led to reduction of NT-proBNP. These data indicate a potential role of NT-proBNP in assessing disease severity, treatment efficacy and prognosis in CHRF.

Topics: Aged; Biomarkers; Carbon Dioxide; Case-Control Studies; Chronic Disease; Female; Humans; Hypercapnia; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Partial Pressure; Peptide Fragments; Prognosis; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; Treatment Outcome

N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore, a clinically useful algorithm for risk stratification based on NT-proBNP as a continuous variable has not yet been described. We therefore evaluated NT-proBNP as a risk marker for mortality and hospitalization and developed a simple algorithm for risk stratification based on NT-proBNP as a continuous variable.. Data from 345 patients with chronic heart failure were collected prospectively in our heart failure clinic, and the patients were followed for 28 months (median). Seventy patients died, and 201 patients were hospitalized. Cox proportional hazard models for mortality and hospitalization were constructed with NT-proBNP as a dichotomous (median 1381 pg/mL) and a continuous variable (log2 NT-proBNP).. Patients with supramedian levels of NT-proBNP had a 2.40-fold (95% CI 1.40-4.10) increased risk for mortality and 1.71-fold (95% CI 1.24-2.36) increased risk for hospitalization. The effect of doubling NT-proBNP on adjusted hazard ratios was 1.56 (95% CI 1.32-1.85) for mortality and 1.19 (95% CI 1.09-1.31) for hospitalization. We observed a curvilinear relationship between NT-proBNP and risk for mortality and hospitalization in the whole range of NT-proBNP.. N-terminal pro-brain natriuretic peptide predicts risk for hospitalization and mortality. A simple algorithm indicates that every time NT-proBNP is doubled, estimated hazard ratio for death increases by a factor of 1.56 (56%) and by a factor of 1.19 (19%) for hospitalization. Finally, the relationship between NT-proBNP and risk is curvilinear if NT-proBNP is considered as a continuous variable.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Risk Assessment; Survival Rate

Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to identify RV dysfunction in CTEPH patients. Therefore, plasma BNP levels were studied in relation to cardiac remodeling and function as determined by cardiac magnetic resonance imaging (MRI).. Thirty-eight patients with CTEPH (55 +/- 15 years), and ten healthy controls (46 +/- 15 years) were studied. The BNP was determined by an immunoradiometric assay.. The CTEPH patients had a mean pulmonary artery pressure of 49 +/- 13 mm Hg, cardiac index 2.1 +/- 0.7 l x min(-1) x m(-2), and pulmonary vascular resistance of 867 +/- 432 dynes x s x cm(-5). In CTEPH patients, compared with controls, right ventricular (RV) remodeling was demonstrated. In the patients, BNP was increased and correlated (all p < 0.0001; Spearman rank test) with MRI parameters of RV remodeling and function: end diastolic (r = 0.71) and end systolic (r = 0.74) volumes, RV mass (r = 0.68), leftward ventricular septal bowing (r = -0.80) and ejection fraction (EF; r = -0.81). By receiver operating curve analysis, BNP levels of 11.5 picomole (pmol)/L and 48.5 pmol/L, respectively, detected RV dysfunction as defined by RVEF less than 0.45 and less than 0.30, respectively, with high sensitivity and specificity. Hemodynamically, BNP levels greater than 48.5 pmol/L identified the most severely affected patients.. In CTEPH patients, BNP levels correlate with RV remodeling and can be used to identify RV dysfunction. Future studies are warranted on the role of BNP to identify "high risk" CTEPH patients and its relation to postoperative hemodynamic outcome, RV failure, and mortality.

Topics: Adult; Aged; Atherectomy; Biomarkers; Cardiac Catheterization; Chronic Disease; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Artery; Thromboembolism; Ventricular Dysfunction, Right

Aortic regurgitation (AR) causes left ventricular (LV) volume overload, leading to progressive LV dilatation and dysfunction. In the present study it was examined whether blockade of angiotensin II type 1 receptor (AT1) could improve survival in cases of chronic severe AR.. AR was induced by puncturing the aortic valves of wild-type (WT) and AT1a knockout (KO) mice. Mice that survived for 4 weeks after the operation were deemed to be a model of chronic severe AR and were followed up for 50 weeks (WT, n=29; KO, n=31). Baseline measurements made 4 weeks after surgery showed similar LV cavity and function in both genotypes. These conditions progressively worsened in both genotypes, but 16 weeks after baseline, KO mice showed significantly less LV dilatation, hypertrophy and interstitial fibrosis than WT mice. Cardiac mRNA expression of B-type natriuretic peptide and type I collagen was lower in KO than WT mice. The 50-week mortality rate was significantly lower among KO (45.2%) than WT (86.2%) mice, and postmortem findings indicated that the lower mortality was attributable to a lower incidence of congestive heart failure.. In cases of chronic severe AR, blockade of AT1 attenuates the progression of LV dilatation, hypertrophy and fibrosis, thereby mitigating heart failure and improving long-term survival.

Topics: Animals; Aortic Valve Insufficiency; Chronic Disease; Disease Models, Animal; Heart Failure; Mice; Mice, Knockout; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 1; RNA, Messenger; Survival Rate; Ventricular Dysfunction, Left; Ventricular Remodeling

Cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) each predict adverse cardiac events in chronic heart failure (CHF). However, little is known about the utility of these novel biomarkers of CHF in combination.. : We hypothesized that simultaneous assessment of the three biomarkers would enable clinicians to stratify risk more effectively among patients with advanced CHF.. Measurements of the biomarkers were performed on 152 patients with symptomatic advanced CHF. Major adverse cardiac events during a median follow-up period of 186 days were determined.. Univariate and multivariate analysis revealed that elevations of each biomarker were significant predictors of clinical outcome independently of clinical variables. When patients were categorized on the basis of the number of elevated biomarkers, patients with one, two and three elevated biomarkers respectively had a 2.7-(p = 0.125), 8.6- (p < 0.0001) and 23.4-(p < 0.0001) fold increase in the risk of adverse events.. Simultaneous measurement of cTnI, hsCRP, and NT-proBNP could provide complementary information and a simple multimarker strategy that categorizes the patients with advanced CHF based on the number of elevated biomarkers, allowing rapid risk stratification in these patients.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Research Design; Risk Assessment; Risk Factors; Troponin I

This study aims to evaluate the role of NT-proBNP and six minute walking distance (6MWD) in the pre- and post-operative assessment of subjects undergoing pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH).. Subjects undergoing PEA between August 2004 and July 2006 were assessed at baseline and 3 months post-operatively with resting haemodynamics, NT-proBNP and 6MWD.. A number of 111 subjects underwent surgery, of which 102 were included. 15 subjects died before their 3 month assessment. Non-survivors had significantly worse preoperative NT-proBNP and 6MWD (4728 pg/mL vs 1863 pg/mL, p=0.001, 182.4 m vs 263.5 m, p=0.001). Taking pre-operative cut-off values of 1200 pg/mL for NT-proBNP and 345 m for 6MWD, both tests had high negative predictive value for predicting mortality (97.3% and 100%, respectively). Amongst survivors, peri-operative changes in NT-proBNP and 6MWD correlated with changes in total pulmonary resistance (TPR) (r=0.49, p<0.001 and r=-0.46, p<0.001). Post-operatively, both NT-proBNP and 6MWD also correlated with mPAP (r=0.65, p<0.001 and r=-0.50, p<0.001) and PVR (r=0.63, p<0.001 and r=-0.47, p<0.001). The ability of NT-proBNP to predict persistent pulmonary hypertension was significantly confounded by age, but not gender, BMI or renal function.. Pre-operative evaluation with NT-proBNP and 6MWD helps risk-stratify patients prior to PEA. Post-operatively, both markers correlate with changes in disease burden and right ventricular function. These results suggest that both NT-proBNP and 6MWD offer effective 'bedside' tools for the long term follow up of patients with CTEPH.

Topics: Aged; Chronic Disease; Endarterectomy; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Postoperative Period; Predictive Value of Tests; Pulmonary Artery; Pulmonary Embolism; Time Factors; Ventricular Dysfunction, Right; Ventricular Pressure

Topics: Acute Disease; Biomarkers; Chronic Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels.. In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 +/-0.4 vs 1.8+/-0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01).. A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Flow Velocity; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Mitral Valve; Natriuretic Peptide, Brain; Ventricular Function, Left

Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF).. To evaluate the prognostic role of CT-1 in patients with CHF.. We measured the plasma levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9 years. Plasma levels of CT-1 increased with severity of CHF. There was a significant negative correlation between plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High plasma levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with plasma BNP>170 pg/mL and CT-1>658 fmol/mL was 2.48 (95% confidence interval, 1.217-5.060) compared to those with plasma BNP>170 pg/mL and CT-1<658 fmol/mL (p=0.0124).. These findings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cytokines; Female; Heart Failure; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; RNA, Messenger; Stroke Volume

Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR.. We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using multiple linear regression models.. Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P <0.0001), and left ventricular ejection fraction (P <0.0001) were associated with log(NT-proBNP). After adjustment for GFR estimated by the Cockcroft and Gault equation, the parameter estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became insignificant, but BMI (P = 0.0067) remained significant and unchanged. The eGFR(MDRD) is adjusted for body surface area, which may explain the difference.. In CHF patients, the effect of age on NT-proBNP is associated with estimates for GFR derived from serum creatinine, and the significance of the effects of BMI on NT-proBNP depends on the method by which GFR is estimated.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Body Mass Index; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce.. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points.. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points.. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

Topics: Adrenergic beta-Antagonists; Aged; Cardiac Output, Low; Catecholamines; Chronic Disease; Female; Follow-Up Studies; Heart Transplantation; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis; Prospective Studies; Time Factors

Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.

Topics: Animals; Biomarkers; Chronic Disease; Disease Models, Animal; Female; Follow-Up Studies; Heart Failure; Humans; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Protein Precursors; Rabbits; RNA, Messenger; Species Specificity; Ventricular Dysfunction, Left

This study evaluates the prognostic utility of renal dysfunction estimated by the recently validated modification of diet in renal disease (MDRD) equations and compares it with the currently most promising predictor of prognosis in patients with advanced heart failure.. We prospectively studied 182 consecutive patients with advanced chronic heart failure (CHF) referred for consideration of cardiac transplantation, with a median follow-up of 642 days. Glomerular filtration rate (GFR) was estimated using the MDRD equations and plasma taken for NT-proBNP analysis. The primary endpoint of all-cause mortality was reached in 40 patients (13.2% crude 1-year mortality), and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 44 patients. The mean GFR estimated by MDRD-1 was 58 mL/min/1.73 m(2). The median NT-proBNP concentration was 1505 (517-4014) pg/mL. Although GFR estimated by MDRD-1 was a univariate marker of all-cause mortality, the only predictor of either endpoint independent of other variables was an NT-proBNP concentration above the median.. NT-proBNP appears superior to GFR estimated by MDRD in patients with advanced CHF. Moreover, NT-proBNP was able to identify patients with a poor prognosis whose GFR was already low.

Topics: Biomarkers; Chronic Disease; Epidemiologic Methods; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Our aim was assess the prognostic value of midregional pro-atrial natriuretic peptide (MR-proANP) using a new immunoassay in patients with chronic heart failure (HF).. Assessment of natriuretic peptides represents a useful addition in establishing the diagnosis of chronic HF. Their plasma values are powerful predictors of survival in chronic HF.. We assessed MR-proANP in 525 chronic HF patients (derivation study: age 61 +/- 12 years, New York Heart Association (NYHA) functional class I/II/III/IV 6%/44%/41%/9%, N-terminal pro-B-type natriuretic peptide (NT-proBNP) 3,637 +/- 6,362 pg/ml) and validated our findings in 249 additional chronic HF patients (age 63 +/- 9 years, NYHA functional class I/II/III/IV 14%/50%/33%/3%, NT-proBNP 1,116 +/- 1,991 pg/ml).. The MR-proANP levels (mean 339 +/- 306 pmol/l, range 24.5 to 2,280 pmol/l) increased with NYHA functional class (p < 0.0001). During follow-up (>6 months in survivors), 171 patients (33%) died. Increasing MR-proANP was a predictor of poor survival (risk ratio 1.35 per increase in standard deviation, 95% confidence interval 1.17 to 1.57; p = 0.0061), adjusted for NT-proBNP, age, left ventricular ejection fraction, NYHA functional class, creatinine, and body mass index (BMI). In receiver operating characteristic curve analysis of 12-month survival, the area under the curve for MR-proANP was 0.74 and that of NT-proBNP was 0.75 (p = 0.7). In a validation study, MR-proANP levels above the optimal prognostic cutoff value from the validation cohort remained a significant independent predictor of death. In chronic HF patients in NYHA functional class II to III and all subgroups of BMI and kidney function, MR-proANP added prognostic value to NT-proBNP. In patients with BMI > or =30 kg/m2, MR-proANP had higher prognostic power than NT-proBNP.. Midregional proANP is an independent predictor of mortality in patients with chronic HF. Midregional proANP adds prognostic information to NT-proBNP.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Survival Rate

Left atrial (LA) volume and B-type natriuretic peptide (BNP) represent powerful outcome predictors in patients with heart failure (HF).. To assess the comparative prognostic role of LA volume (indexed to body surface area, LAVi), left ventricular diastolic dysfunction (LVDD) and BNP levels on long-term outcome in patients with symptomatic but stable chronic HF. methods: We studied consecutively 46 patients with symptomatic stable chronic HF (73 +/- 10 years, 30 men), in sinus rhythm, without significant valvular disease. Echocardiographic measurements included: LV mass, LV volumes and ejection fraction, and LAVi. LVDD was graded using a comprehensive Doppler algorithm. Blood taken before echocardiography was assayed for BNP levels. Primary end point was combined: all-cause mortality and hospitalization for worsening HF.. During 20 +/- 14 months of follow-up 19 events occurred: 8 deaths, and 11 hospitalizations for HF. In univariate analyses LAVi, LVDD, BNP levels, LV ejection fraction, LV volumes, and LV mass were significant outcome predictors (P < 0.05). At multivariate regression LAVi was the only independent predictor of outcome (hazard ratio: 1.03 per 1 ml/m(2) increase, 95% CI: 1.01-1.06, P = 0.02).. Although directly related to LVDD and to BNP levels, only LAVi emerged as an independent outcome predictor in this cohort of elderly patients with symptomatic stable chronic HF.

Topics: Aged; Cardiac Volume; Chronic Disease; Diastole; Echocardiography, Doppler, Pulsed; Female; Follow-Up Studies; Heart Atria; Heart Failure, Diastolic; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

No previous study has compared the transcardiac gradient of cardiac natriuretic peptides and prognosis.. To compare the prognostic value of the transcardiac increase in brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in patients with chronic heart failure (CHF), the hemodynamic parameters and plasma levels of BNP and NT-proBNP were measured in the aortic root (AO) and coronary sinus (CS) in 353 consecutive patients with CHF. During a median follow-up of 2.8 years, 35 patients died. The molar ratio of (CS-AO) NT-proBNP to (CS-AO) BNP correlated with hemodynamic abnormalities and it was significantly higher in non-survivors than in survivors (median value=0.702 vs 0.437, respectively; p=0.0009), suggesting that NT-proBNP is superior to BNP in terms of transcardiac increase. After adjustment for clinical variables associated with CHF, including hemodynamics and an estimated glomerular filtration rate, it was found that only the plasma NT-proBNP level was an independent prognostic predictor, even after considering the transcardiac increases in BNP and NT-proBNP.. These findings suggest that the transcardiac gradient of NT-proBNP to BNP molar ratio increases with the severity of left ventricular dysfunction, and that plasma NT-proBNP level may be more useful than BNP for evaluating the prognosis of patients with CHF.

Topics: Adult; Aged; Aorta; Biomarkers; Chronic Disease; Coronary Sinus; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Ventricular Dysfunction, Left

To evaluate whether NT-proBNP levels are associated with resting hemodynamic parameters assessed by thoracic electrical bioimpedance (TEB) in patients with chronic heart failure (CHF).. We studied 55 consecutive patients with dilated cardiomyopathy and CHF--42 male, aged 50.3 +/- 13.5 years, 39% ischemic, 36% in NYHA functional class III and 9% in class IV, left ventricular ejection fraction 24.7 +/- 8.2%, 85% in sinus rhythm. After 15 minutes of rest, NT-proBNP was obtained and TEB studies were performed (BioZ ICG Monitor, CardioDynamics; mean of 20 minutes acquisition). Thoracic fluid content (TFC) is a TEB parameter that shows a good correlation with pulmonary capillary wedge pressure.. NT-proBNP levels ranged from 42 to 12983 pg/ml (mean = 2505.8, SD = 2608.0, median = 1545). The correlations obtained presented in the table.. In patients with CHF resting NT-proBNP levels correlate with SVI, LCWI and TFC assessed by TEB, the strongest correlation being with TFC.

Topics: Chronic Disease; Electric Impedance; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

We set out to evaluate whether changes in N-terminal pro-brain natriuretic peptide (proBNP) can predict changes in functional capacity, as determined by cardiopulmonary exercise testing (CPET), in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM).. We studied 37 patients with CHF due to DCM, 81% non-ischemic, 28 male, who performed symptom-limited treadmill CPET, with the modified Bruce protocol, in two consecutive evaluations, with determination of proBNP after 10 minutes rest prior to CPET. The time between evaluations was 9.6+/-5.5 months, and age at first evaluation was 41.1+/-13.9 years (21 to 67). RESULTS IN THE FIRST AND SECOND EVALUATIONS RESPECTIVELY WERE: NYHA functional class >II 51% and 16% (p<0.001), sinus rhythm 89% and 86.5% (NS), left ventricular ejection fraction 24.9+/-8.9% and 26.6+/-8.6% (NS), creatinine 1.03+/-0.25 and 1.09+/-0.42 mg/dl (NS), taking ACE inhibitors or ARBs 94.5% and 100% (NS), beta-blockers 73% and 97.3% (p<0.001), and spironolactone 89% and 89% (NS). We analyzed the absolute and percentage variation (AV and PV) in peak oxygen uptake (pVO2--ml/kg/min) and proBNP (pg/ml) between the two evaluations.. (1) pVO2 AV: -17.4 to 15.2 (1.9+/-5.7); pVO2 PV: -56.1 to 84% (11.0+/-25.2); proBNP AV: -12850 to 5983 (-778.4+/-3332.5); proBNP PV: -99.0 to 379.5% (-8.8+/-86.3); (2) The correlations obtained--r value and p value [r (p)]--are shown in the table below; (3) We considered that a coefficient of variation of pVO2 PV of >10% represented a significant change in functional capacity. On ROC curve analysis, a proBNP PV value of 28% showed 80% sensitivity and 79% specificity for pVO2 PV of >10% (AUC=0.876, p=0.01, 95% CI 0.75 to 0.99).. In patients with CHF due to DCM, changes in proBNP values correlate with variations in pVO2, as assessed by CPET. However, our results suggest that only a proBNP PV of >28% predicts a significant change in functional capacity.

Topics: Adult; Aged; Chronic Disease; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Peptide Fragments; Prospective Studies

Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear.. We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured.. The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age.. Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.

Topics: Adult; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain

Immune system activation and oxidative stress are involved in the pathogenesis of heart failure (HF). We aimed to test the hypothesis that upgrading from right ventricular pacing (RVp) to biventricular pacing (BiVp) can counteract these phenomena.. 28 HF patients, with BiVp were switched to RVp for one week, and then returned to BiVp. Immediately prior to, and 48 h after the return to BiVp, left ventricular (LV) systolic function was evaluated by echocardiography, and serum N-terminal pro-brain natriuretic peptide (NTproBNP), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL6), nitric oxide metabolites (NO(x)) and malondialdehyde (MDA) were assayed.. LV systolic function significantly improved 48 h after switching from RVp to BiVp: Ao-VTI (p<0.001), SV (p<0.001) and CO (p<0.001), and mitral regurgitation significantly decreased (p=0.003). At the same time, indices of peripheral immune activation decreased: TNF-alpha (p=0.02) and IL6 (p<0.001). MDA decreased (p<0.001), whereas NO(x) increased (p=0.04). NTproBNP and CRP did not change. In addition, in "responders" (i.e. CO increase >10% during BiVp vs. RVp) NTproBNP decreased and NO(x) increased. However, during BiVp, the decreases in TNF-alpha, IL6, and MDA occurred both in responders and in non-responders and were accompanied by a reduction in mitral regurgitation.. The beneficial effect of BiVp compared to RVp extends beyond improving cardiac haemodynamics and comprises a decrease in immune activation accompanied by an increase in serum NO(x) and decrease in serum MDA.

Topics: Aged; Aged, 80 and over; Cardiac Output, Low; Cardiac Pacing, Artificial; Chronic Disease; Female; Heart Ventricles; Humans; Inflammation; Interleukin-6; Male; Malondialdehyde; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Pacemaker, Artificial; Systole; Tumor Necrosis Factor-alpha; Ventricular Function, Left

Topics: Alprostadil; Biomarkers; Cardiotonic Agents; Chronic Disease; Cytokines; Dose-Response Relationship, Drug; Heart Failure; Humans; Hydrazones; Natriuretic Peptide, Brain; Pyridazines; Simendan; Stroke Volume; Vasodilator Agents

Congestive heart failure (CHF) is associated with marked endothelial dysfunction. We hypothesized that acute and chronic CHF may manifest different degrees of endothelial damage/dysfunction and activation, as reflected by different plasma endothelial markers, such as von Willebrand factor (vWF) and soluble thrombomodulin (both are indexes of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation). Second, we hypothesized a relation between endothelial markers and B-type natriuretic peptide (BNP, an index of cardiac function) in acute and chronic CHF that could be linked to prognosis. To test this hypothesis, we studied 35 patients with acute CHF, 40 patients with chronic CHF, and 32 healthy controls. The patients with CHF were followed up for the combined outcomes of cardiovascular death, nonfatal myocardial infarction, stroke, thromboembolism, and recurrent admissions to the hospital. vWF (p = 0.001), soluble thrombomodulin, E-selectin, and BNP (all p <0.0001) were higher in patients with acute and chronic CHF compared with controls. When the 2 CHF groups were compared, no significant differences were found in vWF or E-selectin (p = NS), but soluble thrombomodulin was significantly elevated in acute CHF (Tukey's post hoc test, p <0.05). Only high vWF was associated with a poorer outcome (log-rank test, p = 0.0188). None of the endothelial indexes correlated with plasma BNP. After a median follow-up of 18 months, only high (median or higher) vWF levels were predictive of adverse outcomes in the patients with CHF (log-rank statistic = 5.52, degree of freedom 1, p = 0.0188). In conclusion, despite similar ejection fractions, patients with acute and chronic CHF have different degrees of endothelial damage/dysfunction and activation, which may be related to differences in pathophysiology. High levels of vWF were associated with a worse short-term outcome. These endothelial markers were unrelated to plasma BNP levels and may imply a different release mechanism.

Topics: Acute Disease; Aged; Biomarkers; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; E-Selectin; Endothelium, Vascular; Female; Follow-Up Studies; Heart Failure; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Admission; Prognosis; Stroke Volume; Thrombomodulin; von Willebrand Factor

Further investigations are warranted to better characterize variables that may confound the clinical interpretation of plasma natriuretic peptide measurements, which are increasingly recognized to have diagnostic and predictive importance.. Blood samples (EDTA plasma) from patients (n = 206) attending clinics for the medical treatment and follow-up of obesity were analyzed for B-type natriuretic peptide (BNP; Bayer assay) and the N-terminal segment of its prohormone (NT-proBNP; Roche assay). Natriuretic peptide concentration ranges were evaluated in those without diagnosis of congestive heart failure (CHF) or chronic kidney disease (CKD).. BNP and NT-proBNP were directly correlated (r = 0.87; P = 0.01), with NT-proBNP concentrations higher relative to BNP. Of obese patients without CHF or CKD, 21.6% (40 of 185) had NT-proBNP concentrations greater than the published assay upper reference limit. Concentrations of both natriuretic peptides were higher in patients currently exposed to beta blockers, patients with the diagnosis of hypertension or type 2 diabetes, and patients with a history of gastric bypass surgery. An inverse relationship between body mass index (BMI) and both BNP and NT-proBNP was evident. According to the National Institutes of Health, National Heart, Lung, and Blood Institute classification, more than 95% of the participants sampled in this study were either obesity class 2 (35 kg/m(2) < BMI < 39.9 kg/m(2)) or class 3 (BMI >or=40 kg/m(2)). A substantial proportion of obese patients without CHF or CKD have concentrations greater than the upper reference limit for NT-proBNP but not for simultaneously measured BNP. A history of gastric bypass surgery appeared to be a significant predictor of increased natriuretic peptide concentrations when assessed in a population of patients with class 2 or 3 obesity.

Topics: Adult; Body Mass Index; Chronic Disease; Cross-Sectional Studies; Female; Gastric Bypass; Heart Failure; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Reference Values

Heart failure is responsible for a huge burden in hospital care. Our goal was to evaluate the value of N-terminal-pro-brain natriuretic peptide (Nt-proBNP) on predicting death or hospital readmission after hospital discharge in patients with chronic heart failure (CHF).. From March 2003 to April 2005, 135 consecutive patients (97 male and 38 female, mean age 60.7 years +/- 13.1 years) with chronic heart failure [dilated cardiomyopathy (44%) and coronary heart disease (35%)] were included in this study. Plasma concentrations of the Nt-proBNP were measured by ELISA on admission. All patients received conventional therapy and were followed up for 24 months. The primary end point was death or readmission.. (1) During the follow up period (640 days +/- 100 days), 11 patients died and 39 patients rehospitalized, the median Nt-proBNP level on admission was significantly higher in patients died during the follow up period (5908 ng/L) than that of rehospitalized patients (2768 ng/L, P = 0.038). Plasma Nt-proBNP level on admission were significantly higher in primary end point group (n = 50, 2947 ng/L) than that in non-primary end point group (n = 85, 917 ng/L, P < 0.01). (2) Variables associated with an increased hazard of death and/or rehospitalization were Nt-proBNP and NYHA degree when analyzed by logistic regression models. Increased Log Nt-proBNP was the strongest independent predictor of an adverse outcome of CHF (odds ratio 13.8, 95% confidence interval 2.29 to 2.78, P < 0.01). (3) Area under the curve for Nt-proBNP in evaluating prognosis of CHF patients was 0.885 (positive predictive value 88.5%, negative predictive value 11.5%).. Nt-proBNP level on admission is a strong predictor of rehospitalization and death within 24 months after hospital discharge in patients with chronic heart failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiac Output, Low; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Function; Young Adult

To study the relationship of the level of N-terminal portion of brain natriuretic (NT-ProBNP) with the treatment and prognosis of patients with acute attack of chronic left heart failure.. Patients (age range 18-80 years) with decompensated heart failure treated in the emergency department in Fuwai Hospital were included in this study. Dynamic changes of plasma levels of NT-ProBNP, angiotensin (AO), renin activity (PRA), angiotensin II (AT II) and aldosterone (ALD) were detected by enzyme linked immunoadsorbent assay (ELISA) before anti-cardiac failure treatment and 3-5, 5-7 days after the treatment. All enrolled patients were followed up for 2 years after leaving hospital, and cardiovascular events such as death, myocardial infarction, worsening of heart failure, severe arrhythmia or delayed discharge from hospital were recorded.. Compared with baseline level at admission, plasma NT-ProBNP levels were lowered on 3rd -5th day and 5th-7th day after admission and treatment (both P<0.05) in 44 patients with chronic left heart failure, but there was no difference in NT-ProBNP levels between the 3rd-5th and 5th -7th day after treatment. The levels of plasma NT-ProBNP increased much higher at all observation times in patients with cardiovascular events than without the events (all P<0.05), but the changes in AO, PRA, ATII and ALD showed no significant difference between two groups (all P>0.05).. During acute onset, plasma NT-ProBNP levels in patients with chronic left heart failure can be lowered at 3-7 days after admission and treatment. Higher baseline levels of plasma NT-ProBNP may have certain predictive values for long term prognosis in patients with chronic left heart failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Young Adult

Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) are elevated in severe mitral regurgitation, but their relation to functional capacity and cardiac remodeling is not well defined. We evaluated the role of NT-pro-BNP as a marker of functional capacity, symptoms, and cardiac remodeling in 38 patients with severe degenerative mitral regurgitation and preserved left ventricular ejection fraction. The NT-pro-BNP levels increased progressively with New York Heart Association (NYHA) functional class: NYHA class I (geometric mean [GM] 97.1 pg/ml), NYHA class II (GM 169.8 pg/ml), and NYHA III (GM 457.6 pg/ml; p = 0.015). The end-systolic volume index (r = 0.52, p = 0.001), end-diastolic volume index (r = 0.46, p = 0.003), left atrial volume index (r = 0.4, p = 0.01), regurgitant volume index (r = 0.38, p = 0.02), regurgitant fraction (r = 0.46, p = 0.003), and end-diastolic sphericity index (r = 0.56, p <0.001) all correlated significantly with NT-pro-BNP. The NT-pro-BNP levels correlated significantly with the exercise parameters: maximum oxygen uptake (r = -0.6, p <0.001), exercise time (r = -0.52, p <0.001), and oxygen pulse (r = -0.57, p <0.001). In contrast, only weak correlations were obtained between the exercise and echocardiographic variables. NT-pro-BNP was a strong independent predictor of maximum oxygen uptake (p = 0.001). In conclusion, the results of this study have demonstrated that NT-pro-BNP increases progressively with worsening symptoms, is linked to the extent of LV remodeling, and is an independent predictor of functional capacity. NT-pro-BNP may have a role in the optimal treatment of patients with severe mitral regurgitation.

Topics: Analysis of Variance; Biomarkers; Chronic Disease; Echocardiography; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments

Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure.. Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP.. In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.

Topics: Aged; Cardiac Output, Low; Chronic Disease; Endothelin-1; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Osmolar Concentration; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Severity of Illness Index

The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NT-proBNP in patients with chronic and stable HF.. We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves.. NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P=0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P=0.032) or hospitalization for HF (P=0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696.. The natriuretic peptides BNP and NT-proBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF.

Topics: Aged; Biomarkers; Cardiac Output, Low; Chronic Disease; Female; Humans; Linear Models; Male; Multicenter Studies as Topic; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; ROC Curve; Severity of Illness Index

This study assessed the relation between B-type natriuretic peptide (BNP) and echocardiographic indexes of left ventricular (LV) filling pressure in 53 patients with stable heart failure and without significant valvular dysfunction. Left atrial volume indexed to body surface area (LAVi), an indicator of chronic LV filling pressure, was correlated with BNP (r = 0.692, p <0.001) and was the strongest independent predictor of elevated levels in this cohort. LAVi was also the best predictor of BNP >or=100 pg/ml, with an area under the receiver-operating characteristic curve of 0.85 (95% confidence interval 0.74 to 0.96, p <0.001). Using the optimal cutoff of >31 ml/m(2), LAVi had a sensitivity of 92% and a specificity of 65% for BNP >or=100 pg/ml. Patients with LAVi >31 ml/m(2) had a median BNP of 122 pg/ml, compared with 21 pg/ml in patients with LAVi

Topics: Aged; Atrial Function, Left; Biomarkers; Body Surface Area; Chronic Disease; Cohort Studies; Female; Heart Atria; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Regression Analysis; Stroke Volume; Ultrasonography

The prognostic role of serum C-reactive protein (CRP) in chronic heart failure (CHF) patients, especially those with nonischemic dilated cardiomyopathy (DCM), remains unknown. In the present study, whether CRP provides prognostic information in DCM patients was evaluated.. Neurohumoral factors and hemodynamics in 84 consecutive DCM patients were measured and these patients were followed up for a mean period of 42 months. During the follow-up period, 23 patients developed cardiac events and 18 patients died of cardiac causes. Using stepwise multivariate Cox proportional hazards regression analyses, log brain natriuretic peptide (BNP) (p = 0.007) and high-sensitivity CRP (hsCRP) > 1 mg/L (p = 0.008) were significant independent predictors of cardiac events. The patients were stratified into 4 groups based on the normal serum concentration of hsCRP (1 mg/L) and median plasma concentration of BNP (110 pg/ml). Survival rates were significantly higher in patients with hsCRP < 1 mg/L and BNP < 110 pg/ml. The hazard ratio of patients with BNP > 110 pg/ml and hsCRP > 1 mg/L was 15.8 (95% confidence interval, 1.9-127.2) compared with those with BNP < 110 pg/ml and hsCRP < 1 mg/L for cardiac death.. Serum hsCRP level is an independent prognostic predictor in patients with DCM and the combination of hsCRP and BNP may be useful for the management of CHF patients with DCM.

Topics: C-Reactive Protein; Cardiomyopathy, Dilated; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Survival Rate

To determine whether acute left ventricular dysfunction (LVD) causes significantly higher elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than comparable chronic LVD.. Plasma levels of NT-proBNP were measured in 10 pediatric patients diagnosed with acute LVD, in 7 pediatric patients with stable chronic dilated cardiomyopathy (DCM) and comparable levels of echocardiographic dysfunction, and during 5 episodes of acute exacerbation in patients with heart failure. Levels were compared using Mann-Whitney and analysis of variance for rank tests.. Plasma levels of NT-proBNP were excessively elevated in patients with acute LVD in the first 24 to 48 hours of hospitalization (median level, 65,600 pg/mL), and were significantly higher than those in patients with chronic DCM (median level, 1125 pg/mL; P < .0001). NT-proBNP levels decreased in the subsequent days in 83% of patients with serial measurements. The NT-proBNP levels were lower In 5 episodes of acute exacerbation than in acute LVD (median level, 7185 pg/mL; P < .003).. Acute LVD is associated with elevated NT-proBNP level in children.

Topics: Acute Disease; Adolescent; Adult; Cardiomyopathies; Child; Child, Preschool; Chronic Disease; Heart Failure; Hospitalization; Humans; Infant; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Ventricular Dysfunction, Left

N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a predictor of prognosis in patients with left ventricular dysfunction. Although a similar prognostic significance has been suggested in 1 study of right ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP has not been assessed as a marker of disease severity in a more heterogenous group of patients with chronic precapillary pulmonary hypertension (PH). Hence, this study assessed plasma NT-pro-BNP and other clinical variables in 61 consecutively recruited patients with various forms of chronic precapillary PH. Right-sided cardiac catheterization and cardiopulmonary exercise testing were performed at baseline, and the prognostic significance of NT-pro-BNP was investigated with a mean follow-up of 25 months. Compared with age-matched controls (n = 10), plasma NT-pro-BNP was significantly greater in those with idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH associated with other diseases (n = 26), and chronic thromboembolic disease (n = 19) and was correlated with hemodynamic variables and functional capacity. In 17 medically treated patients, the significant decrease in NT-pro-BNP levels correlated with improved hemodynamics. During follow-up, 15 patients died from cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of mortality. Kaplan-Meier survival analysis according to the median value of NT-pro-BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with supramedian values than in those with low plasma levels (p = 0.010). In conclusion, these findings suggest that in a heterogenous group of patients with chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical severity of disease and is independently associated with long-term mortality.

Topics: Biomarkers; Cardiac Catheterization; Chronic Disease; Exercise Test; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Pulmonary Wedge Pressure; ROC Curve; Severity of Illness Index; Survival Rate; Time Factors

Type V phosphodiesterase (PDE V) metabolizes cyclic guanosine monophosphate (cGMP) and is abundant in the kidney and vasculature and was found recently in the heart. Sildenafil is a PDE V inhibitor that is used clinically for erectile dysfunction. Brain natriuretic peptide (BNP) is a cardiac peptide with vasodilating, lusitropic, and natriuretic properties that are mediated via cGMP. It was hypothesized that chronic inhibition of PDE V (PDE VI) will enhance the renal actions of exogenous BNP by potentiating the renal cGMP. The cardiorenal and humoral function was determined at baseline in two groups of dogs with pacing-induced overt chronic heart failure (CHF; 240 bpm for 10 d): Group 1 (n = 6) received Sildenafil 50 mg orally three times daily during the 10 d of pacing, and group 2 (n = 5) received no PDE V inhibitor. The response to acute subcutaneous BNP (5 microg/kg) administration also was compared in both groups on day 11. The GFR was assessed by inulin clearance (P < 0.05). There was no improvement of renal function in group 1 after 10 d of PDE VI as compared with group 2, despite having higher cardiac output (P < 0.05). Group 1 had significantly higher plasma (44 +/- 2 versus 21 +/- 3 pmol/ml; P < 0.05) and urinary cGMP (4219 +/- 900 versus 1954 +/- 300 pmol/min; P < 0.05) as compared with group 2. With acute subcutaneous BNP administration, group 1 had a natriuretic and diuretic response that was associated with an increase in GFR (30 +/- 6 to 45 +/- 6 ml/min; P < 0.05) and that was not observed in group 2 (25 +/- 6 to 29 +/- 4 ml/min). Plasma BNP increased to a similar extent in both groups with subcutaneous BNP. In contrast, group 1 had a much greater urinary cGMP excretion (4219 +/- 900 to 8600 +/- 1600 pmol/min; P < 0.05) as compared with group 2 (1954 +/- 300 to 3580 +/- 351 pmol/min; P < 0.05). In experimental overt CHF, chronic administration of PDE V inhibitor did not enhance renal function despite an improvement in cardiac output. However, chronic PDE VI significantly enhanced the renal hemodynamic and excretory responses to exogenous BNP. This study supports a role for PDE V as contributing to renal maladaptation in a model of experimental overt CHF and the strategy of maximizing the renal cGMP system by combined PDE VI and natriuretic peptides in CHF to improve renal function.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Chronic Disease; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclic Nucleotide Phosphodiesterases, Type 5; Dogs; Heart Failure; Kidney; Male; Natriuretic Peptide, Brain; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

This study compared the correlation and prognostic utility of B-type natriuretic peptide (BNP) and the N-terminal fragment of proBNP (NT-proBNP) in 171 outpatients with renal dysfunction. The NT-proBNP correlated well with BNP in all cases (r = 0.911; P pound .01), regardless of degree of renal impairment or type of left ventricular dysfunction. BNP and NT-proBNP concentrations (P < .005) and their ratios (P pound .01) increased as the glomerular filtration rate (GFR) declined, indicating a greater effect of GFR on NT-proBNP levels. Both natriuretic peptide levels were higher in patients with systolic dysfunction (P < .05) compared with patients with normal echocardiograms. In contrast, BNP and NT-proBNP levels were below the diagnostic cutoffs for congestive heart failure exacerbations in patients with normal heart function or diastolic dysfunction, with no statistical difference between these groups (P = .99). Both peptides are useful prognostic tools for predicting mortality and cardiac hospitalization in renal patients.

Topics: Aged; Biomarkers; Chronic Disease; Female; Hospitalization; Humans; Kidney Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Survival Rate; Ventricular Dysfunction, Left

Chronic kidney disease (CKD) is common in systolic heart failure (SHF) and is associated with poor outcomes. It is also associated with underuse of angiotensin-converting enzyme (ACE) inhibitors, yet the effect of these drugs in these (SHF-CKD) patients has not been well studied. The objective of this analysis was to determine if ACE inhibitor use was associated with reduction in mortality and hospitalization in SHF-CKD patients.. Of the 6800 SHF patients (ejection fraction < or = 45%) in the Digitalis Investigation Group trial, 1707 had CKD (serum creatinine 1.3-2.5 mg/dL for women and 1.5-2.5 mg/dL for men). Propensity scores for ACE inhibitor use were calculated for each of the 1707 patients and were used to match 104 of the 127 no-ACE inhibitor patients with 104 ACE inhibitor patients. We estimated the effect of ACE inhibitor use on outcomes at 2 years using multivariable-adjusted Cox regression analyses. Overall, 35% of patients died and 67% were hospitalized. Compared with 30% of ACE inhibitor patients, 39% of no-ACE inhibitor patients died (adjusted HR = 0.58; 95% CI = 0.35-0.96; P = .034). Compared with 64% of ACE inhibitor patients, 69% of no-ACE inhibitor patients had hospitalizations from all causes (adjusted HR = 0.69; 95% CI = 0.48-0.98; P = .040).. We observed an association between use of ACE inhibitor and reductions in mortality and hospitalization in ambulatory chronic SHF patients with mild to moderate CKD. However, the results of this observational study should be interpreted with caution, and need to be replicated in larger and more recent databases, and confirmed prospectively in well-designed follow-up studies and/or randomized clinical trials.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Chronic Disease; Cohort Studies; Female; Hospitalization; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Randomized Controlled Trials as Topic; Severity of Illness Index; Survival Analysis; Systole

Although oxidative stress mediated by reactive oxygen species plays an important role in the pathogenesis of heart failure (HF), good clinical markers for reactive oxygen species in patients with HF have not been established. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is formed from deoxyguanosine in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced in cells as a radical scavenger against oxidative stress. The aim of this study is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients with chronic HF with idiopathic dilated cardiomyopathy (DCM).. We estimated serum 8-OHdG and TRX levels using enzyme-linked immunosorbent assay in 32 patients with DCM and investigated the impact of these markers to the clinical characteristics of these patients. Serum levels of 8-OHdG, but not TRX were significantly correlated with New York Heart Association functional class, left atrial diameters, left ventricular end-diastolic diameters, left ventricular end-systolic diameters, and plasma levels of brain natriuretic peptide.. These data suggest oxidative DNA damage is increased in patients with DCM according to the severity of HF. Serum levels of 8-OHdG may represent clinically useful markers of left ventricular remodeling.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Deoxyguanosine; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Severity of Illness Index; Thioredoxins

Natriuretic peptides, particularly brain natriuretic peptide (BNP), are elevated in heart failure and therefore considered to be excellent predictors of outcome. Vasopressin is also known to be related to the severity of heart disease. Copeptin--an inactive fragment of the vasopressin precursor--has not been previously investigated in the context of heart failure.. We prospectively studied 268 patients with advanced heart failure after they had been discharged from the hospital. We investigated the ability of BNP and copeptin to predict death, re-hospitalization due to heart failure, and a combination of the two endpoints.. Over a mean follow-up period of 15.8 months (up to 24 months), 83 patients died, 122 patients experienced worsening of heart failure, and 145 patients achieved the combined endpoint. Univariate predictors of death were copeptin, BNP, age and impaired kidney function. In multivariate analysis, copeptin (chi(2) = 16, P < 0.0001) and age (chi(2) = 4, P < 0.05) were independent predictors. Univariate predictors of re-hospitalization due to heart failure were copeptin, BNP, age and impaired kidney function. Furthermore, in multivariate analysis BNP (chi(2) = 18, P < 0.0001), age (chi(2) = 11.8, P < 0.001) and copeptin (chi(2) = 4.2, P < 0.05) were found to be independent predictors.. Our study is the first to show that copeptin is an excellent predictor of outcome in advanced heart failure patients. Its value is superior to that of BNP in predicting death and a combined endpoint, although BNP is still suitable for predicting chronic heart failure (CHF) re-hospitalization. Our data imply that vasopressin antagonism might be a new target to improve outcome in this population.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Glycopeptides; Heart Failure; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies

To evaluate asymptomatic patients with chronic Chagas disease to determine prevalence of ventricular arrhythmias, left ventricular dysfunction, and B-type natriuretic peptide (BNP) plasma levels.. One hundred and six patients from the Chagas disease outpatient clinic underwent clinical evaluation, electrocardiogram (ECG), cardiothoracic index (CTI), ambulatory electrocardiogram (Holter monitoring), echocardiogram, and BNP measurement and then were distributed into three groups: GI, with normal ECG (n = 50); GIIA, with ECG changes characteristic of Chagas disease (n = 31); and GIIB, with other ECG changes (n = 25).. The most common electrocardiographic changes were the following. GIIA: complete right bundle branch block (35%), left anterior hemiblock (35%), and electrically inactive areas (32%); GIIB: inferolateral repolarization change (28%), and left ventricular overload (24%). Mean CTI index values were similar (p = 0.383). Ventricular arrhythmia prevalence was higher in the GIIA (77%) and GIIB (75%) groups than in the GI group (46%) (p = 0.002). Ventricular dysfunction was more prevalent in the GIIA (52%) and GIIB (32%) groups than in the GI group (14%) (p = 0.001). Systolic dysfunction was more prevalent in the GIIA group (29%) than in the GIIB (20%) and GI groups (2%) (p < 0.001). Diastolic dysfunction was more prevalent in the GIIA (42%) and GIIB (28%) groups than in the GI group (12%) (p = 0.005). Mean B-type natriuretic peptide levels were 30 +/- 88 pg/mL in the GI group, 66 +/- 194 in the GIIA group and 24 +/- 82 for the GIIB group (p = 0.121), respectively.. Arrhythmias and left ventricular dysfunction are more prevalent in asymptomatic patients with chronic Chagas disease and abnormal ECG than in patients with normal ECG. Plasma BNP levels were similar among the groups.

Topics: Adult; Arrhythmias, Cardiac; Biomarkers; Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Cross-Sectional Studies; Echocardiography; Electrocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Prevalence; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

Little is known about the relationship of body fluid status with the levels and fluctuations of B-type natriuretic peptide (BNP) over the long-term.. If BNP is to become useful for monitoring of patients with chronic heart failure (HF), the levels should reliably reflect both decompensation and improvement in the patient's condition.. Forty-six patients with chronic HF who were stable at study entry but had previous decompensation were recruited and followed up between June 2003 and September 2005. At each visit, they were examined for BNP level and HF-related signs of body fluid retention based on physical evaluation and pleural ultrasonography.. During the study period, 26 patients developed decompensation and 20 maintained a stable clinical course. In the 26 decompensated patients, BNP levels fluctuated widely (110 +/- 73.7 pg/ml; range 25-290 pg/ml) even during stable periods. In all but three patients in this group, the maximum BNP level during decompensation was higher than that reached during stable periods. The BNP levels also fluctuated widely (180 +/- 123 pg/ml; range 16-489 pg/ml) in the 20 stable patients with HF. In all but one patient in this group, the BNP level was lower than the maximum BNP level obtained during the previous decompensation.. In patients with chronic HF with previous decompensation, there was a strong link between the appearance of clinical HF sign(s) of fluid retention and an increased BNP level despite wide intraindividual fluctuations in BNP over time. Thus, BNP levels reliably reflect both decompensation and improvement.

Topics: Aged; Body Fluids; Cardiac Output, Low; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Water-Electrolyte Balance

Since chronic heart failure (CHF) is a complex clinical syndrome, a single biomarker may not reflect all of its characteristics. In this study, the clinical significance of combination and serial measurement of biochemical markers of myocyte injury and myocardial load in patients with CHF from various etiologies was examined. Serum concentrations of cardiac troponin-T (cTnT) and plasma concentrations of brain natriuretic peptide (BNP) were measured simultaneously in 190 patients with CHF, including dilated cardiomyopathy (DCM) (n = 41), ischemic heart disease (n = 40), valvular or congenital disease (n = 53), hypertensive heart disease (n = 16), and hypertrophic cardiomyopathy (HCM) (n = 22). Serum cTnT concentrations >or=0.01 ng/ml were found in 46/190 patients (24%) at baseline (20% in DCM, 42% in ischemic heart disease, 21% in valvular or congenital disease, 43% in hypertensive heart disease, and 9% in HCM). Follow-up samples were obtained in 137 patients after a mean treatment period of 31.8 days. Although BNP decreased significantly in each disease category (P < 0.0001: DCM; P < 0.005: ischemic heart disease; P < 0.05: valvular or congenital disease; P < 0.005: hypertensive heart disease; P < 0.05: HCM), cTnT remained high in 36/137 patients (26%) (19% in DCM, 39% in ischemic heart disease, 25% in valvular or congenital disease, 38% in hypertensive heart disease, and 19% in HCM). The rate of adverse cardiac events was significantly higher in patients with high cTnT than in patients with low cTnT concentrations (P < 0.0001) (P < 0.05: DCM; P < 0.05: ischemic heart disease; P < 0.01: valvular or congenital disease). Multivariate analysis showed that both cTnT and BNP are independent prognostic factors, and patients with elevations of both cTnT and BNP had the poorest prognosis (P < 0.0001). In patients with CHF, the evolution and prognostic value of cTnT and BNP are different. The combined measurements of these markers should refine our understanding of the state and evolution of CHF.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Troponin T

Cardiovascular complications proportionally increase as chronic kidney diseases (CKD) progress into chronic renal insufficiency or failure. The present study addressed whether the long-term use of angiotensin II receptor blocker (ARB) exerts a cardio-protective effect in CKD patients with mild to moderate renal damage.. Fifteen patients with CKD above stage 3 were enrolled in the study. While their previous antihypertensive therapy remained unchanged, the ARB candesartan, was newly added to the concurrent therapy and the patients were followed for 12-24 months thereafter.. The main results were as follows: 1) The use of ARB improved the status of BP control classifications, shifting them to the better control categories where there was less morning hypertension. 2) ARB significantly reduced the left ventricular (LV) mass index(LVMI), the relative wall thickness (RWT), the LV intra-dimension in diastole(LVIDd), and as a result, the LV ejection fraction(LVEF) improved. In parallel, the LV mass category shifted to lower categories, indicating a significant improvement. 3) The levels of BNP decreased significantly from 135.2 +/- 136.0 to 85.0 +/- 80.3 pg/mL. 4) ARB reduced urinary protein excretion in all cases. Regardless of an inevitable increase in the serum creatinine(Cr) concentration, the slope of reciprocal serum Cr concentration (l/Cr) in the treatment period with ARB was significantly less steep compared to that in the run-in period. 5) Throughout the observation period, no serious side effects were found in any of the patients.. The present study indicated that the long-term use of ARB exerts both cardio-, and renoprotective effects in patients with advanced CKD. This agent could be especially indicative and useful not only for patients with CKD, but also for patients of CKD with cardiac hypertrophy.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Cardiomegaly; Chronic Disease; Female; Humans; Kidney Diseases; Male; Natriuretic Peptide, Brain

Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an alpha-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF.

Topics: Cardiomyopathy, Dilated; Chronic Disease; Disease Progression; Echocardiography; Female; Glucose Intolerance; Glucose Tolerance Test; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Severity of Illness Index

Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion.. NT-proBNP and BNP were measured in a nonconsecutive patient cohort receiving clinically indicated intravenous nesiritide. Blood samples were drawn before, at 6 and 24 h during, and at 6 h after infusion. A reduction in NT-proBNP was defined as a decrease from baseline during infusion ("infusion responders") of >3 SD of the variability of the assay measurement (approximately 20%). Patients with decreases >20% in both NT-pro BNP and BNP at 6 h post infusion were designated "biochemical responders".. Forty patients [27 males; mean (SE) age, 68 (2) years; mean (SE) left ventricular ejection fraction, 25 (1.4)%] were studied. All patients improved clinically. Overall, the changes in NT-proBNP were a 18 (4.6)% [mean (SE)] and 19.8% (median) decrease from baseline at 24 h of infusion and a 22 (6.0)% and 17.8% decrease at 6 h post infusion (P <0.001 compared with baseline). In a large number of patients, decreases in NT-proBNP were, however, within the variability of the assay. Subgroup analysis showed that 22 of 40 patients were infusion responders with a >20% decrease from baseline in NT-proBNP during nesiritide infusion, whereas only 12 patients were biochemical responders with >20% decreases from baseline postinfusion for both NT-proBNP and BNP.. In this study, many patients had decreased NT-proBNP and BNP values after therapy with nesiritide, but the majority of patients did not demonstrate biochemically significant decreases in analytes despite a clinical response. Until we know more about the responses of natriuretic peptides to therapies such as nesiritide, a strategy of monitoring NT-proBNP and BNP to guide therapy cannot be universally advocated.

Topics: Aged; Biomarkers; Chronic Disease; Cohort Studies; Drug Monitoring; Female; Heart Failure; Humans; Immunoassay; Infusions, Intravenous; Luminescent Measurements; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Recombinant Proteins; Treatment Outcome

The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population.. Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death.. cTn-T (> or =0.03 microg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (> or =0.03 microg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01).. BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the "real world" situation.

Topics: Acute Disease; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Predictive Value of Tests; Prognosis; Troponin T

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Chronic Disease; Circadian Rhythm; Comorbidity; Continuous Positive Airway Pressure; Heart Failure; Humans; Natriuretic Peptide, Brain; Oxygen; Polysomnography; Sleep Apnea Syndromes; Wakefulness

Topics: Adult; Biomarkers; Case-Control Studies; Chronic Disease; Disease Progression; Echocardiography, Doppler; Female; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

A noninvasive marker of disease severity and presence of symptoms is required in patients with chronic rheumatic valve disease (RVD).. We sought to test the utility of measuring of N-terminal pro-B type natriuretic peptide (NT-proBNP) in chronic phase RVD. We also evaluated whether echocardiographic measures are interrelated with NT-proBNP levels.. The study comprised 92 patients with RVD (mean age of 40+/-14 years) and 50 age/gender-matched control subjects. Functional status was assessed. Detailed echocardiographic examination was performed and mitral valve score was estimated. Venous blood samples were taken for measuring the level of NT-proBNP.. The plasma levels of NT-proBNP rose with increasing severity of mitral valve stenosis (p<0.001), increasing severity of mitral valve score (p<0.001), increasing severity of clinical symptom (p<0.001), increasing severity of mitral regurgitation (p<0.013), presence of mitral valve calcification (p<0.001), presence of tricuspid valve stenosis (p<0.001), increasing severity of tricuspid regurgitation (p<0.011), presence of aortic stenosis (p=0.043), decreasing left ventricular ejection fraction (p<0.001), presence of left atrial thrombus (p=0.0019), and with increasing left atrium dimensions (p=0.002).. NT-proBNP levels in patients with chronic RVD are a potential marker of disease severity and correlates with symptoms.

Topics: Adolescent; Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Rheumatic Heart Disease; Ultrasonography

B-type natriuretic peptide (BNP) is an established tool for the diagnosis of acute congestive heart failure in patients presenting with dyspnea. Some patients have moderately elevated BNP levels (ie, 100 to 500 pg/mL) in the absence of acute congestive heart failure. The objective of the current study was to identify independent predictors of elevated BNP concentrations in the absence of congestive heart failure.. We studied 781 patients without acute congestive heart failure and BNP levels 0 to 500 pg/mL drawn from a cohort of 1,586 patients with acute dyspnea who had BNP levels measured on emergency department arrival. Two cardiologists blinded to BNP results reviewed all clinical data and categorized patients according to whether they had acute congestive heart failure or not.. Independent predictors of elevated BNP levels (ie, >100 pg/mL) were a medical history of atrial fibrillation, radiographic cardiomegaly, decreased blood hemoglobin concentration, decreased body mass index, and increased age.. Knowledge of these commonly obtained variables should aid clinicians in the interpretation of moderately elevated BNP results in patients presenting with acute dyspnea in the emergency department.

Topics: Aged; Arrhythmias, Cardiac; Biomarkers; Chronic Disease; Comorbidity; Dyspnea; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Embolism; Respiration Disorders; Retrospective Studies

To study the clinical significance of plasma adrenomedullin (ADM) and brain natriuretic polypeptide (BNP) in the patients with chronic cor pulmonale on highland (HACCP).. The levels of ADM and BNP in plasma of 44 patients with HACCP in the acute and in the remission stages were determined with radioimmunoassay. Their correlations with partial pressure of oxygen in arterial blood (PaO(2)), endothelin-1 (ET-1), and the ratio of right ventricular pre-ejection time to the pulmonary flow acceleration time (RVPEP/AT), which reflected the degree of pulmonary hypertension, were investigated. Twenty healthy subjects served as a normal control group.. The levels of ADM [(38.8+/-7.2)ng/L and (26.2+/-5.3)ng/L] and BNP [(81.4+/-13.8)ng/L and (58.9+/-9.3)ng/L] in the acute and remission stages of cor pulmonale groups were both significantly higher than those in the normal control group [(15.0+/-3.2)ng/L, (38.6+/-3.4)ng/L, respectively, all P<0.01]. The levels of ADM and BNP in acute stage were both significantly higher than those in remission stage (both P<0.01). In the acute and in the remission stages, the levels of ADM in plasma were negatively correlated with PaO(2) (r(a)=-0.826, P<0.01; r(r)=-0.783, P<0.01), positively correlated with ET-1 (r(a)=0.755, P<0.01; r(r)=0.668, P<0.01) and RVPEP/AT ratio (r(a)=0.788, P<0.01; r(r)=0.734, P<0.01). In the acute and in the remission stages, the levels of BNP in plasma were negatively correlated with PaO(2) (r(a)=-0.787, P<0.01; r(r)=-0.554, P<0.01), positively correlated with ET-1 (r(a)=0.725, P<0.01; r(r)=0.679, P<0.01) and RVPEP/AT ratio (r(a)=0.771, P<0.01; r(r)=0.722, P<0.01).. The study suggests that ADM and BNP are involved in the pathophysiological process of HACCP in the patients and may play a compensatory role in the disease.

Topics: Adrenomedullin; Aged; Altitude; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Heart Disease

N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level predicts underlying heart disease in the general population. However, because NT-proBNP clearance may depend on renal function, the significance of an elevated level in patients with chronic kidney disease (CKD) without cardiac symptoms is uncertain. We sought to determine whether there is an association between NT-proBNP level and coronary artery disease (CAD) and left ventricular hypertrophy (LVH) in this population.. We enrolled 207 ambulatory patients with CKD not on dialysis therapy. Medical records were reviewed for cardiac history and risk factors. NT-proBNP and troponin T (cTnT) levels were measured. Echocardiograms were analyzed from 99 patients.. NT-proBNP levels were elevated in 116 patients (56%), and 67 patients (33%) had experienced prior CAD events (myocardial infarction or revascularization). The prevalence of advanced age, diabetes, prior CAD events, myocardial injury (cTnT > 0.03 ng/mL [>0.03 microg/L]), and LVH increased, whereas glomerular filtration rate decreased, across quartiles of NT-proBNP levels. After adjustment for glomerular filtration rate, cTnT level, age, and diabetes, NT-proBNP remained an independent indicator of prior CAD events compared with quartile 1 (cTnT range, 4 to 116 pg/mL) for quartile 2 (range, 122 to 490 pg/mL): odds ratio, 1.6; 95% confidence interval, 0.5 to 5.0; for quartile 3 (range, 490 to 1,819 pg/mL): odds ratio, 5.3; 95% confidence interval, 1.7 to 16.2; and for quartile 4 (>1,975 pg/mL): odds ratio, 4.1; 95% confidence interval, 1.3 to 13.5. For patients with echocardiograms, NT-proBNP level predicted prior CAD events independent of LVH.. NT-proBNP level elevation in asymptomatic patients with CKD reflects underlying ischemic heart disease and hypertrophy independent of renal function in a population with anticipated high cardiac morbidity.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Comorbidity; Coronary Disease; Creatinine; Ethnicity; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prospective Studies; Retrospective Studies; Risk Factors; Ultrasonography

Topics: Acute Kidney Injury; Aged; Cardiotonic Agents; Chronic Disease; Digoxin; Emergency Medicine; Fatal Outcome; Female; Heart Failure; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Natriuretic Peptide, Brain

Topics: Adult; Chronic Disease; Electrocardiography; Heart Failure; Homocysteine; Humans; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Severity of Illness Index

A common key question in clinical medicine is whether coronary artery disease (CAD) is present in a patient. This applies not only to patients with symptomatic chest pain, but also to those at high risk of sudden unexpected death due to asymptomatic CAD, such as diabetics. In both groups of patients, it would be of great benefit if a simple blood test could identify those most likely to have CAD. Such individuals could then be selected for more definitive but more invasive tests for CAD, such as angiography, exercise testing, etc. In addition to its established role in diagnosing heart failure, it appears that BNP may fulfil this function of pre-screening for both symptomatic and asymptomatic CAD. We review the evidence for this new prospect, which has the potential to reduce cardiac deaths by using a simple blood test to better target cardioprotective strategies to those who most need them.

Topics: Biomarkers; Chronic Disease; Coronary Disease; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Reproducibility of Results

We sought to determine the safety and efficacy of repeated 60 degrees C sauna bathing in patients with chronic systolic congestive heart failure (CHF).. This study included 15 hospitalized CHF patients (New York Heart Association class = 2.8 +/- 0.4) in stable clinical condition on conventional treatments. Sauna bathing was performed once per day for 4 weeks. Repeated sauna bathing was safely completed without any adverse effects in all patients. Symptoms improved in 13 of 15 patients after 4 weeks. Sauna bathing decreased systolic blood pressure without affecting heart rate, resulting in significant decrease in the rate-pressure product (6811 +/- 1323 to 6292 +/- 1093). Echocardiographic left ventricular ejection fraction was significantly increased from 30 +/- 11 to 34 +/- 11%. Sauna bathing significantly improved exercise tolerance manifested by prolonged 6-minute walking distance (388 +/- 110 to 448 +/- 118 m), increased peak respiratory oxygen uptake (13.3 +/- 1.8 to 16.3 +/- 2.1 mL/kg/min), and enhanced anaerobic threshold (9.4 +/- 1.2 to 11.5 +/- 1.9 mL/kg/min). Four-week bathing significantly reduced plasma epinephrine (40 +/- 42 to 21 +/- 23 pg/mL) and norepinephrine (633 +/- 285 to 443 +/- 292 pg/mL). Sauna bathing reduced the number of hospital admission for CHF (2.5 +/- 1.3 to 0.6 +/- 0.8 per year).. Repeated 60 degrees C sauna bathing was safe and improved symptoms and exercise tolerance in chronic CHF patients. Sauna bathing may be an effective adjunctive therapy for chronic systolic CHF.

Topics: Adult; Aged; Anaerobic Threshold; Biomarkers; Blood Pressure; Chronic Disease; Epinephrine; Exercise Tolerance; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Patient Admission; Quality of Life; Steam Bath; Stroke Volume; Systole; Treatment Outcome

Natriuretic peptides are promising markers in diagnosing acute and chronic heart failure and assessing prognosis in these patients. Increasing routine use to unselected patients is challenged by false-positive results. The aims of this study were to assess (a) the distributions of N-terminal B-type natriuretic peptide (NT-proBNP) values in various diagnostic groups, (b) factors that influence NT-proBNP, and (c) the value of NT-proBNP in risk stratification in unselected emergency room (ER) patients.. NT-proBNP was measured in 876 unselected consecutive patients [mean (SD) age, 58 (18) years; 53% male] attending the ERs of 2 university hospitals and 1 community hospital. Diagnoses, age, sex, hemoglobin, creatinine (CREA), C-reactive protein (CRP), troponin T, and intensity of care were documented. In a subset consisting of all 417 patients at 1 center, in-hospital follow-up was completed with respect to a complicated clinical course, including intensive care treatment and death.. NT-proBNP was significantly increased in patients with cardiac diagnoses or histories compared with patients with only pulmonary or other diagnoses. In patients with other diagnoses, NT-proBNP values increased significantly with the number of atherosclerotic risk factors (P=0.044). Age, renal function, CRP, and to a much lesser extent, hemoglobin significantly influenced NT-proBNP values. The amount of care was positively correlated with NT-proBNP (P<0.001). Classification and regression tree analysis showed a superior impact of NT-proBNP for identification of high-risk patients.. NT-proBNP is a promising marker for identification of patients with structural heart disease in the ER and a suitable tool for risk stratification. Its use in the ER should be limited to clearly clinically defined patient groups at present to avoid a potential excess of additional diagnostic procedures in positive but asymptomatic patients.

Topics: Acute Disease; Age Factors; Biomarkers; C-Reactive Protein; Chronic Disease; Creatinine; Emergency Medical Services; Female; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Troponin T

To investigate the diagnostic and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and atrium natriuretic peptide (ANP) in chronic congestive heart failure.. Seventy-one coronary heart disease patients were enrolled in the study. Among them 58 patients were accompanied by heart failure and 13 with no heart failure. Plasma NT-ProBNP was determined with enzyme linked immunoadsorbent assay method, and plasma ANP was determined with radioimmunoassay method. The results were compared with those of 30 healthy individuals. All patients were followed up accordingly.. Compared with patients with no heart failure and healthy individuals, the patients with heart failure had a higher plasma NT-proBNP and ANP contents. Cardiac function grade IV patients had a significantly higher plasma NT-ProBNP than cardiac function grade II and III patients, and their plasma ANP level was significantly higher than that of cardiac function grade III patients, but there was no significantly difference in ANP content between cardiac function grade IV and II. The diagnostic sensitivity of NT-proBNP and ANP was 94.38% and 75.86%, respectively. The diagnostic specificity of NT-proBNP and ANP was 96.67%, 83.33%, respectively. In the heart failure group, after being followed up for (11.35+/-1.69) months, it was found that there was no significant difference in the plasma NT-proBNP and ANP between the deaths and surviving patients.. The diagnostic value of NT-proBNP in chronic heart failure is higher than that of ANP. According to our follow-up result, the plasma NT-proBNP and ANP can not be relied upon to predict short-term cardiogenic death in heart failure.

Topics: Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Recent studies have suggested that higher body mass index (BMI) is associated with improved prognosis in chronic heart failure (CHF). The adipocytokine adiponectin is inversely associated with BMI, and in healthy subjects, low adiponectin is a predictor of mortality. In a prospective study, we therefore evaluated the association between plasma adiponectin levels and mortality among patients with CHF.. In 195 CHF patients (age 69.3+/-10.2 years, BMI 27.3+/-5.2 kg/m2, left ventricular ejection fraction 30+/-8.9%, mean+/-SD), plasma adiponectin and N-terminal pro brain natriuretic peptide (NT-proBNP) were measured at baseline. Adiponectin was positively associated with NT-proBNP (beta=0.47, P<0.001), and both biomarkers were negatively associated with BMI (beta=-0.43, P<0.001 for adiponectin and beta=-0.38, P<0.001 for NT-proBNP, respectively) During a median follow-up of 2.6 years, 46 (23.5%) of the patients died. After adjustment for clinical variables associated with CHF severity (age, systolic blood pressure, left ventricular ejection fraction <25%, duration of CHF, and creatinine clearance) and for NT-proBNP, the hazard ratio of mortality for values in the 2 upper tertiles relative to the lowest tertile of adiponectin was 3.23 (P=0.032). BMI predicted mortality independently of clinical parameters of CHF severity (hazard ratio=0.63, P=0.012), but this association became insignificant after additional adjustment for NT-proBNP (hazard ratio=0.74, P=0.13).. A high adiponectin level was a predictor of mortality, independent of risk markers of CHF severity, presumably because of its role as a marker for wasting. BMI was also associated with mortality, but a part of this relation may be mediated by adiponectin and NT-proBNP levels.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Regression Analysis; Survival Analysis

It is a prevailing concept in chronic heart failure (CHF) that ventricular remodelling (evaluated via imaging) and neurohormonal activation (via biomarkers) exert major influences, such that the need to subject patients to haemodynamic evaluations and exercise testing has been questioned. We sought to investigate whether exercise and haemodynamic parameters lack independent prognostic value in a cohort of unselected ambulatory patients with mild-moderate CHF.. Eighty-five consecutive patients with stable CHF in New York Heart Association functional classes I-IV, aged 55 +/- 12 years, 84% males, left ventricular ejection fraction (LVEF) 37 +/- 15%, participated in this study. Survivors were followed for a median of 5.08 years. All subjects underwent cardiopulmonary exercise testing to measure standard parameters including peak oxygen consumption, exercise duration and blood pressure. A sample of venous blood was taken to determine the N-terminal pro-brain natriuretic peptide (N-BNP) level. Echocardiography was performed at rest to measure LVEF. Predictors of mortality were sought using the Cox proportional hazards model.. All-cause mortality was 19% (16 deaths, 95% CI 11-29%). Age and LVEF did not independently predict mortality. Although various parameters including New York Heart Association class, peak oxygen consumption and N-BNP level were all predictive of outcome on univariate analysis, multivariate analysis identified reduced exercise duration and peak systolic blood pressure (SBP) to be the only independent predictors of all-cause mortality. Hazard ratios of 0.78 (95% CI 0.65-0.93, p = 0.007) and 0.79 (95% CI 0.66-0.95, p = 0.01) were associated with an increase in exercise duration of 1 min and 10 mm Hg peak SBP, respectively.. Two simple parameters (exercise duration and peak SBP) that are easily measured by standard exercise testing are the strongest independent predictors of mortality which outperform LVEF and N-BNP in ambulatory patients with mild-moderate CHF.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Chronic Disease; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Oxygen Consumption; Physical Endurance; Predictive Value of Tests; Proportional Hazards Models; Research Design; Severity of Illness Index; Stroke Volume; Survival Analysis; Systole; Ultrasonography; Ventricular Dysfunction, Left

The aim of this study was to assess the predictive potency of impaired endothelium-dependent flow-mediated vasodilation (FMD) in patients with chronic heart failure (CHF).. Chronic heart failure is associated with reduced FMD; the prognostic impact of this observation is unknown.. Seventy-five ambulatory CHF patients (United Network of Organ Sharing [UNOS] status 2) with a left ventricular ejection fraction (LVEF) < or =30%, despite optimized medical therapy (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 100%; beta-blocker, 81%), were evaluated. Using high-resolution ultrasound, FMD of the brachial artery was assessed in addition to other neurohormonal, clinical, and hemodynamic variables. Age, gender, New York Heart Association (NYHA) functional class, LVEF, hemodynamic variables, B-type natriuretic peptide (BNP) levels, medical therapy, cardiovascular risk factors, and FMD were analyzed for prediction of the combined end point conversion to UNOS status 1 or death in a multivariate Cox model.. Up to three years, 21 patients (28%) converted to UNOS status 1, and 6 patients (8%) died. Univariate risk factors for the combined end point were log BNP (p = 0.0032), FMD (p = 0.0033), NYHA functional class (p = 0.0132), beta-blocker therapy (p = 0.0367), and mean blood pressure (p = 0.0406). In the multivariate analysis, only FMD (p = 0.0007), log BNP (p = 0.0032), and mean blood pressure (p = 0.0475) were independently related to the combined end point. In the Kaplan-Meier plot, significantly more patients with FMD <6.8% (median) reached the combined end point, as compared with patients with FMD >6.8% (p = 0.004).. In CHF, impaired FMD is a strong, independent predictor of conversion to UNOS status 1 or death.

Topics: Adult; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Regional Blood Flow; Ultrasonography; Vasodilation

Elevated plasma natriuretic peptides in heart failure (HF) usually indicate a poor outcome and low levels a compensated state. In advanced chronic HF, however, low levels may reflect an impaired neurohormonal response. To assess this hypothesis, this study analyzed whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and B-type natriuretic peptide (BNP) levels were related to mortality in 40 patients treated for decompensated chronic HF. Cardiovascular mortality during follow-up (10 +/- 1 months) was 40%. BNP levels were lower in patients who died (487 +/- 60 vs 836 +/- 99 pg/ml, p <0.02), as were NT-pro-BNP levels (9,507 +/- 1,178 vs 17,611 +/- 4,338 pg/ml, p <0.05). These data support the hypothesis that patients with end-stage HF and poor short-term survival have lower natriuretic peptide levels than those who survive. These findings suggest that the natriuretic peptide system can no longer contribute adequately to neurohormonal compensation and that paradoxically low peptide levels are an adverse prognostic marker in advanced HF.

Topics: Aged; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Predictive Value of Tests; Survival Rate; Treatment Outcome

Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2).. Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35.. Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01).. In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.

Topics: Aged; Chronic Disease; Exercise Test; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Ventilation; Reproducibility of Results

Most patients with chronic kidney disease (CKD) develop cardiovascular complications. Natriuretic peptides are novel markers that can be used to identify and monitor heart failure, but the effect of renal disease on these markers is not fully understood. The aim of the present study is to explore the relationship among circulating B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) concentrations and clinical variables in a cohort of patients with CKD.. Plasma BNP and NT-proBNP concentrations and left ventricular (LV) mass index were measured in 213 predialysis patients with CKD.. Plasma BNP and NT-proBNP concentrations increased with declining estimated glomerular filtration rate (GFR; P < 0.0001). Estimated GFR had an independent effect on plasma BNP (P = 0.0028) and, to a greater extent, plasma NT-proBNP (P < 0.0001) concentrations: mean BNP concentration increased by 20.6% per 10-mL/min/1.73 m2 (0.17-mL/s) reduction in estimated GFR compared with 37.7% for NT-proBNP. NT-proBNP/BNP ratio increased with CKD stage (P < 0.0001). Median plasma BNP and NT-proBNP concentrations were greater in patients with LV hypertrophy (P < 0.0001), and LV mass index had an independent effect on both BNP (P = 0.0223) and NT-proBNP (P < 0.0017).. Estimated GFR and LV mass index have independent effects on both plasma BNP and NT-proBNP concentrations in patients with CKD. NT-proBNP appears to be affected more by declining kidney function, in keeping with the hypothesis that its clearance is predominantly renal. Our data have significant implications for application of these peptides as cardiac biomarkers in patients with CKD.

Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Cohort Studies; Comorbidity; Female; Glomerular Filtration Rate; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Kidney; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Prospective Studies; Single-Blind Method; Stroke Volume; Ultrasonography

Microalbuminuria is associated with increased risk for cardiovascular morbidity and mortality. However, the relation between microalbuminuria and chronic heart failure has not been well described yet. In this cross-sectional study, we aim to evaluate the prevalence of microalbuminuria and the association with neurohormonal parameters in severe chronic heart failure patients.. We studied 94 stable chronic heart failure patients (New York Heart Association class III/IV) receiving therapy with angiotensin-converting enzyme (ACE) inhibitors for over three months. In all patients, renal function and neurohormonal status were evaluated and correlated with urinary albumin/creatinine ratio. The studied population consisted of 70 men and 21 women (mean age 69 +/- 12 years). Ischemia was the underlying cause of heart failure in 61 patients. Overall, 100% of the patients were treated with an ACE inhibitor, 72% with a beta-blocker, and 47% with spironolactone. In 32% (95% confidence interval 22-42) of the patients, microalbuminuria was present, which is significantly higher than in the general population. However, we found no significant association between the presence of microalbuminuria and renal function. Plasma NT-proBNP, active renin protein, angiotensin I, angiotensin II, and aldosterone did not differ significantly between groups with and without microalbuminuria.. In 32% of the patients, microalbuminuria was present. No association was found with either renal or neurohormonal parameters.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Albuminuria; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prevalence; Renin; Research Design; Spironolactone; Treatment Outcome

The mechanisms of cardiac remodeling during chronic heart failure remain poorly defined. We sought to advance a chronic canine model of nonischemic cardiomyopathy.. Male dogs (n = 6) received decremental right ventricular apical tachypacing (12 months) to achieve and maintain stable left ventricular (LV) dysfunction. After 10 months of tachypacing, 120 beats/min was sufficient to maintain stable LV dysfunction. Electrocardiography, echocardiography, and tissue Doppler imaging were done to evaluate electrophysiology, LV dimensions and function, and dyssynchrony during normal sinus rhythm. The 6-minute walk test was used to evaluate functional capacity. We observed increases in both QRS duration (P < .0001) and QRS amplitude (P < .0001). LV fractional shortening was reduced from a baseline of 38.0 +/- 1.4% to 11.2 +/- 1.4% (P < .0001). LV end-diastolic dimension increased from 3.8 +/- 0.1 cm at baseline to 5.3 +/- 0.3 cm (P < .0001); LV end-systolic dimension increased from 2.3 +/- 0.1 cm to 4.7 +/- 0.2 cm (P < .0001). LV mass increased from 85.9 +/- 3.5 g at baseline to 179 +/- 13.7 g (P < .0001). There was evidence of LV dyssynchrony (P < .04) during both normal sinus rhythm and right ventricular tachypacing, compared with control dogs. The distance a dog walked in 6 minutes was significantly less at 12 months compared with normal controls (540 +/- 32 m versus 277 +/- 64 m, P < .008).. This nonischemic model of canine cardiomyopathy reproduces many aspects of chronic human heart failure including reduced fractional shortening, dilated ventricular dimensions, increased LV mass, decreased functional capacity, and dyssynchrony.

Topics: Animals; Biomarkers; C-Reactive Protein; Cardiomyopathies; Chronic Disease; Disease Models, Animal; Dogs; Echocardiography, Doppler; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Hypertrophy, Left Ventricular; Male; Models, Cardiovascular; Natriuretic Peptide, Brain; Research Design; Stroke Volume; Time Factors; Troponin C; Troponin I; Ventricular Dysfunction, Left; Ventricular Remodeling

To determine the predictive power of B-type natriuretic peptide (BNP) regarding death in older, functionally impaired patients with multiple comorbidity.. Prospective cohort study.. Specialist geriatric assessment clinic and day hospital.. Two hundred ninety-nine older, functionally impaired patients, mean age 79 at enrollment.. Full clinical history and examination, baseline BNP, and echocardiography. Date and cause of death were ascertained from Scottish death records. Kaplan-Meier survival curves were constructed for quartiles of log (BNP), and the contribution of BNP to prediction of death was investigated.. The follow-up period ranged from 3.9 to 5.2 years (mean 4.4 years). BNP was a powerful independent predictor of all-cause and cardiovascular mortality. BNP was a more powerful predictor than blood pressure, diabetes mellitus, smoking, echocardiographic left ventricular hypertrophy, left ventricular systolic dysfunction, or age. BNP predicted death in those with and without a previous cardiovascular event at baseline.. BNP has significant predictive power for death in older, functionally impaired patients.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Chronic Disease; Cohort Studies; Disabled Persons; Female; Frail Elderly; Geriatric Assessment; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Radioimmunoassay; Scotland; Survival Analysis

The accuracy of the tissue Doppler E/Ea and color M-mode Doppler E/Vp indexes in diagnosing congestive heart failure (HF) was investigated in 20 chronic hypertensive patients with acute dyspnea and normal left ventricular ejection fractions who met Vasan's criteria for definite diastolic HF, compared with 20 gender- and age-matched hypertensive patients with noncardiac cause of acute dyspnea. The E/Ea ratio appeared to be more reproducible (variability 4% to 9% vs 6 to 14%) and more precise (sensitivity 77.8%, specificity 100%, and accuracy 89.5% for the optimal cutoff of 11 vs sensitivity 73.7%, specificity 75%, and accuracy 74.3% for the optimal cutoff of 1.5) than the E/Vp ratio in this clinical setting.

Topics: Aged; Aged, 80 and over; Blood Flow Velocity; Chronic Disease; Coronary Angiography; Coronary Artery Disease; Echocardiography; Echocardiography, Doppler, Color; Emergency Medical Services; Female; Heart Failure; Humans; Hypertension; Male; Mitral Valve; Natriuretic Peptide, Brain; Observer Variation; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Stroke Volume; Ventricular Function, Left

It is evident, that overt thyroid dysfunction (both, hypo- or hyperthyroidism) could be associated with heart failure. The aim of our study was to establish whether also mild changes in free thyroxin (fT4) may influence the degree of heart failure in patients with chronic heart insufficiency.. There were included 148 patients (m 121, f 27, mean age 63.8 +/- 1.14) with clinical chronic heart failure were, with fT4 levels within the normal range (9-22 pmol/l) and without thyroid suppression or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and big endothelin. Patients with fT4 in the range 11.9-14.6 pmol/l (optimal, 3rd-6th decile) had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 (low-normal, bottom two deciles) (1236 +/- 223.6 pg/ml; p < 0.03) and those with fT4 over 14.6 pmol/l [high-normal, top four deciles] (1192 +/- 114.9 pg/ml; p < 0.0002). These differences remain significant also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were found also in BNP and high endothelin, but only between optimal and high-normal fT4 strata.. The degree of heart failure could be influenced also by mild changes in fT4 concentration.

Topics: Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Thyroxine; Ventricular Dysfunction, Left

We investigated the correlations between exercise intolerance and the plasma levels of neurohormonal factors and proinflammatory cytokines in chronic heart failure (CHF) patients. Sixty-two CHF patients who underwent cardiopulmonary exercise testing (CPX) were enrolled in this study. Peak oxygen uptake (peak VO2) and the plasma concentrations of noradrenaline (NA), brain natriuretic peptide (BNP), and soluble tumor necrosis factor receptors I and II (TNFR-I and -II) were all measured during the CPX. The patients were divided into three groups according to their peak VO2; a severe exercise intolerance group (severe group; peak VO2 < 18 mL/min/kg), moderate exercise intolerance group (moderate group; 18 24). There were no significant differences in left ventricular ejection fraction (EF) among the three groups. NA and BNP both increased gradually in parallel with the worsening of exercise intolerance (NA, 211.5 +/- 75.7 pg/mL, 331.8 +/- 163.7, 441.9 +/- 202.9, respectively; BNP, 37.9 +/- 25.4 pg/mL, 148.9 +/- 117.1, 247.9 +/- 150.0, respectively). TNFR-I and II were significantly higher in the severe group than in the moderate group (1746.1 +/- 950.7 versus 1085.2 +/- 370.5 pg/mL and 2855.3 +/- 1550.9 versus 2047.7 +/- 648.7 pg/mL, respectively), while the values in the moderate group were not significantly different from those in the mild group. EF showed no significant correlations with NA, BNP, TNFR-I, or TNFR-II, whereas peak VO2 exhibited significant negative correlations with NA (r = -0.50, P < 0.0001), BNP (r = -0.53, P < 0.0001), TNFR-I (r = -0.50, P < 0.0001), and TNFR-II (r = -0.45, P < 0.0001). It is concluded that NA and BNP rise in parallel with the degree of exercise intolerance, while TNFR-I and -II rise only when exercise intolerance reaches severe levels.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Exercise Test; Exercise Tolerance; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

B-type natriuretic peptide (BNP) and the amino-terminal fragment of the BNP prohormone (NT-proBNP) are markers for functional cardiac impairment and are elevated in heart failure (HF). Aim of the present study was to perform a head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease.. We prospectively classified 180 consecutive subjects according to ACC/AHA guidelines. Blood concentrations of BNP and NT-proBNP were determined by two fully automated chemiluminescent assays (Bayer and Roche method). Diagnostic utilities were tested by ROC analyses and logistic regression.. ROC curves of BNP and NT-proBNP in patients with symptomatic HF (n=43) and asymptomatic subjects (n=137) did not differ significantly (AUC 0.930 vs. 0.918, p=0.650), but comparison of patients with asymptomatic structural heart disease (n=56) and subjects without structural disorder of the heart (n=81) revealed different AUCs for the respective assays (0.735 vs. 0.839, p=0.009). In the population studied, age, sex and renal function had no impact on the diagnostic performance of both tests when compared by logistic regression models.. Both assays facilitate diagnosis of symptomatic and asymptomatic structural heart disease. BNP and NT-proBNP may be equally useful as an aid in the differential diagnosis of probable signs or symptoms of HF. In contrast, NT-proBNP might be a more discerning marker of early cardiac dysfunction than BNP.

Topics: Adult; Aged; Area Under Curve; Biomarkers; Chronic Disease; Electrocardiography; Female; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Immunoassay; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Reproducibility of Results

Topics: Acute Disease; Atrial Fibrillation; Chronic Disease; Heart Atria; Humans; Natriuretic Peptide, Brain

The relations between muscle strength, muscle endurance, and cardiopulmonary parameters were investigated in patients with chronic heart failure.. The subjects comprised 33 outpatients with stable chronic heart failure (27 men, 6 women, mean age 60.3 +/- 12.7 years). A pedal-type isokinetic device was used throughout the study. The safety of the study protocol was examined first. Maximum muscle power (peak power), an index of muscle strength, was measured for 6 consecutive revolutions(3 revolutions of each leg). The strength decrement index (SDI) was measured for 20 consecutive maximal revolutions (10 revolutions in each leg). The SDI is an index of muscle endurance and compares the mean power for revolutions 9 and 10 with that for revolutions 2 and 3. Each subjects underwent symptom-limited cardiopulmonary exercise testing with a cycle ergometer on another day.. No subject experienced continuous abnormal heart rate or blood pressure response, chest pain, ischemic ST-T change, or severe arrhythmia. The peak power and the SDI were correlated with the anaerobic threshold (r = 0.42, 0.52, respectively), with peak oxygen uptake (r = 0.66, 0.61), and with the increase in oxygen uptake per unit increase in work rate (r = 0.43, 0.63). However, the slope of the ventilation equivalent to carbon dioxide output was correlated only with the SDI (r = -0.54) and the time constant for the oxygen uptake decrease was correlated only with the peak power (r = -0.46).. Peak functional capacity depends on both muscle strength and endurance, and subjective symptoms in daily activity, especially dyspnea on exertion, depend mainly on muscle endurance in patients with chronic heart failure.

Topics: Aged; Chronic Disease; Exercise Test; Female; Heart Failure; Humans; Leg; Male; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Oxygen Consumption; Physical Endurance; Stroke Volume

Because the real prognosis of Japanese patients with chronic heart failure (CHF) is still unknown, the aim of the present study was to clarify the prognosis and predictors for mortality of CHF patients using the Chronic Heart failure Analysis and Registry in Tohoku district (CHART).. As of February 2003, 1,154 stable CHF patients with optimum standard therapy have been enrolled in the registry since February 2000 and of these, 175 died of some cause during the follow-up period (mean follow-up period, 1.9+/-0.9 years), giving 1- and 3-year all-cause mortality rates of 7.3% and 20.9%, respectively. Multivariate analysis showed that age at entry, diabetes, ventricular tachycardia, plasma concentration of brain natriuretic peptide (BNP), New York Heart Association (NYHA) functional class and rural residence were significantly associated with all-cause mortality (hazard ratio: 1.028, 1.940, 1.650, 1.001, 1.713, and 2.226). The 1-year all-cause mortality rates of CHF patients with a left ventricular ejection fraction <25%, left ventricular end-diastolic diameter > or =60 mm, BNP > or =500 pg/ml, NYHA > or = III, or with underlying coronary artery disease were 15.0%, 11.4%, 16.8%, 16.3%, and 10.8%, respectively.. The prognosis of Japanese CHF patients with these predictors remains poor. A stratified approach is necessary to improve their survival and quality of life.

Topics: Aged; Cardiac Output, Low; Chronic Disease; Coronary Disease; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Registries; Risk Factors; Severity of Illness Index; Stroke Volume

The kinetics of brain natriuretic peptide (BNP) secretion in chronic heart failure (CHF) during dynamic exercise have been the subject of controversial debate. The present study was therefore aimed to further clarify whether marked changes in BNP levels occur during and directly after vigorous exercise in CHF patients.. We prospectively studied 37 patients with CHF (60+/-10 years, LVEF 26+/-6%) and 20 healthy controls (58+/-11 years, LVEF 60+/-3%). Standardized exercise testing was performed in all CHF patients and controls. Venous blood samples for measurement of BNP were obtained prior to symptom-limited exercise, at peak exercise and at 1 and 5 min of recovery time.. BNP concentrations were significantly higher in CHF compared to controls at rest, peak exercise and at 1 and 5 min of recovery. BNP levels did not change significantly during exercise in the control group. In CHF patients, BNP levels showed no marked difference at rest (428+/-421 pg/ml), peak exercise (507+/-450 pg/ml, n.s.), 1 min (560+/-460 pg/ml, n.s.) and 5 min recovery (526+/-424 pg/ml, n.s.). Strikingly, 6 of 37 CHF patients (16%) showed a decrease in BNP at exercise compared to rest but none of the controls.. BNP levels in CHF patients and healthy controls are not significantly altered by vigorous exercise. In contrast to controls, 16% of CHF patients showed a decrease in BNP levels at exercise. In CHF, BNP levels were inversely correlated with peak VO(2), VO(2)-AT and LVEF.

Topics: Aged; Biomarkers; Cardiomyopathy, Dilated; Chronic Disease; Coronary Artery Disease; Exercise; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Prospective Studies; Statistics as Topic; Stroke Volume; Survival Analysis

This study aimed to investigate the prognostic importance of plasma erythropoietin (EPO) levels in chronic heart failure (CHF) patients.. Anemia is common and is associated with an impaired survival in patients with CHF. Erythropoietin is a hematopoietic growth factor, upregulated in anemic conditions. Little is known about the pathophysiology of anemia in CHF and the prognostic importance of plasma EPO levels in CHF patients.. In 74 patients with CHF (age, 61 +/- 2 years; left ventricular ejection fraction, 0.31 +/- 0.01; peak oxygen consumption, 19.1 +/- 0.6 [mean +/- SEM]) and in 15 control patients, hemoglobin levels and plasma concentrations of EPO and brain natriuretic peptide were measured.. During a mean follow-up of 3.0 years (range, 2.3 to 5.3 years), 22 patients (30%) died. Anemia was present in 24% of the patients. Multivariate analysis showed that plasma EPO (p = 0.026) and hemoglobin levels (p = 0.005) were independent predictors of survival in this CHF population. We observed only a mild inverse correlation between the logarithm of EPO and hemoglobin levels (r2 = 0.08, p = 0.02) in CHF patients, whereas the control group showed a clear significant inverse correlation (r2 = 0.44, p = 0.007).. Elevated plasma EPO levels are associated with an impaired prognosis independent of hemoglobin levels and other established markers of CHF severity. Furthermore, in the CHF patients, EPO levels poorly correlate with the hemoglobin levels, in contrast with the control group.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Erythropoietin; Female; Follow-Up Studies; Heart Failure; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Prognosis; Retrospective Studies; Severity of Illness Index; Statistics as Topic; Survival Analysis

We compared brain natriuretic peptide (BNP) levels in patients with obstructive sleep apnea (OSA) with and without cardiovascular disease to BNP in healthy control subjects. OSA was not associated with increased plasma BNP or atrial natriuretic peptide (ANP) in otherwise healthy subjects during wakefulness. Untreated OSA increased ANP overnight, and ANP levels decreased with treatment of OSA. However, OSA did not elicit acute overnight changes in BNP, either in normal subjects or in patients with coexisting cardiovascular disease (including chronic heart failure).

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiovascular Diseases; Chronic Disease; Circadian Rhythm; Comorbidity; Continuous Positive Airway Pressure; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Polysomnography; Reference Values; Sleep Apnea Syndromes; Wakefulness

Serum B-type natriuretic peptide (BNP) levels reflect myocardial strain and are known to be elevated in patients with heart failure. To determine if BNP levels are elevated in patients with aortic regurgitation, we measured BNP levels in patients with chronic asymptomatic aortic regurgitation and normal left ventricular systolic function.

Topics: Adult; Aged; Aortic Valve Insufficiency; Chronic Disease; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function, Left

Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in the diagnosis of heart failure (HF) depends traditionally on whether it is as good as the putative 'gold-standard', left ventricular ejection fraction (LVEF), in indicating cardiac dysfunction. However, since HF is primarily an impairment of function of the cardiac pump, we explored the relationship between N-BNP and direct and indirect indicators of cardiac pump dysfunction.. Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/-15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the study and had resting N-BNP measured. Cardiopulmonary exercise testing was performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects underwent further exercise haemodynamic assessment to evaluate peak cardiac power output (CPO). The CHF group had significantly higher N-BNP (median [interquartile range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml, P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant. Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as independent predictors of peak Vo(2).. We have found that N-BNP was surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart failure is an inadequacy of function, these results strongly support the notion that N-BNP is a useful blood test in estimating the extent of cardiac pump dysfunction and helpful in establishing positive diagnosis of heart failure.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chronic Disease; Exercise Test; Exercise Tolerance; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Research Design; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

To examine the prognostic contribution of combined cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure (CHF) in the absence of acute coronary syndrome.. Between July 2001 and March 2002, 71 consecutive patients (mean age = 68.4+/-1.4 years, 37 men), hospitalised for heart failure, were studied during hospitalisation and follow up until December 2002. Serum cTnT and NT-proBNP were measured on admission. Actuarial rates of adverse cardiac events, including sudden or CHF death, or rehospitalisation for CHF during follow up were compared with patients grouped according to initial serum cTnT and/or NT-proBNP concentrations. The adverse cardiac event-free rate among the 20 patients with cTnT > or 0.01 ng/ml was significantly lower than the 51 patients with cTnT <0.01 ng/ml (P<0.05). Similarly, the adverse cardiac event-free rate among the 36 patients with NT-proBNP > or =1,357 pg/ml (median) was significantly lower than the 35 patients with NT-proBNP <1,357 pg/ml (P<0.01). The 16 patients with high concentrations of both cTnT and NT-proBNP had a lower adverse cardiac event-free rate than the 31 patients with low cTnT and low NT-proBNP upon commencement of the study (P<0.005).. Measurements of serum cTnT and NT-proBNP were reliable prognostic markers of adverse cardiac event in patients with CHF.

Topics: Aged; Cardiac Output, Low; Chronic Disease; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Patient Readmission; Peptide Fragments; Prognosis; Troponin T

Topics: Adolescent; Adult; Biomarkers; Chronic Disease; Echocardiography, Doppler, Color; Electrocardiography; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity; Severity of Illness Index

Data mining is a technique for discovering useful information hidden in a database, which has recently been used by the chemical, financial, pharmaceutical, and insurance industries. It may enable us to detect the interesting and hidden data on useful drugs especially in the field of cardiovascular disease.. We evaluated the current treatments for chronic heart failure (CHF) in our institute using a decision tree method of data mining and compared the results with those of large-scale clinical trials. We enrolled 1,100 patients with CHF (NYHA classes II-IV and EF < 40%) who were hospitalized at the National Cardiovascular Center during the past 31 months. Drugs prescribed at discharge were extracted from the clinical database. Both echocardiograms and plasma BNP level at 6-12 months after discharge were determined prospectively. It was found that beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor antagonists independently improve both the plasma BNP level and %fractional shortening (FS), while oral inotropic agents increased the plasma BNP level and decreased %FS. These findings agree with evidence accumulated from several large-scale trials. Interestingly, statins, histamine receptor blockers, and alpha-glucosidase inhibitors also attenuated the severity of CHF, suggesting the possibility of new treatment of CHF.. Clinical data mining using Japanese CHF patients yielded almost identical data to the results of large-scale trials, and also suggested novel and unexpected candidates for CHF therapy. Further validation of the data mining approved in the cardiovascular field is warranted.

Topics: Chronic Disease; Data Collection; Decision Trees; Drug Combinations; Evidence-Based Medicine; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Research Design; Ventricular Remodeling

Topics: Aged; Chronic Disease; Female; Forecasting; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.

Topics: Atrial Natriuretic Factor; Case-Control Studies; Chronic Disease; Epinephrine; Exercise Test; Female; Heart Failure; Humans; Interleukin-6; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Topics: Atrial Natriuretic Factor; Chronic Disease; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

The continuous IV administration of prostacyclin improves pulmonary hemodynamics and prognosis in patients with primary pulmonary hypertension. We investigated whether the administration of prostacyclin therapy to patients before they undergo pulmonary thromboendarterectomy ameliorates pulmonary hypertension in patients with the most severe form of chronic thromboembolic pulmonary hypertension (CTEPH).. Of the 33 patients with CTEPH who were candidates for pulmonary thromboendarterectomy, 12 patients with severe pulmonary hypertension (pulmonary vascular resistance, > 1,200 dyne. s. cm(-5)) received IV prostacyclin prior to undergoing pulmonary thromboendarterectomy. Right heart catheterization and plasma brain natriuretic peptide (BNP) measurements were repeated at baseline, immediately before surgery, and 1 month after surgery.. During a mean (+/- SEM) follow-up period of 46 +/- 12 days, the IV administration of prostacyclin resulted in a 28% decrease in pulmonary vascular resistance (1,510 +/- 53 to 1,088 +/- 58 dyne. s. cm(-5); p < 0.001) before surgery. Prostacyclin therapy markedly decreased plasma BNP level (547 +/- 112 to 188 +/- 30 pg/mL; p < 0.01), suggesting improvement in right heart failure. Pulmonary thromboendarterectomy caused a further reduction of pulmonary vascular resistance (302 +/- 47 dyne. s. cm(-5)) and plasma BNP levels (60 +/- 11 pg/mL) compared to each preoperative value (p < 0.05). Operative mortality rates were relatively low (8.3%) in patients with the most severe form of CTEPH.. The IV administration of prostacyclin caused beneficial hemodynamic effects in patients with severe CTEPH and may serve as pretreatment for patients undergoing pulmonary thromboendarterectomy.

Topics: Adult; Aged; Antihypertensive Agents; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Endarterectomy; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Premedication; Prognosis; Pulmonary Embolism; Survival Rate; Vascular Resistance

Topics: Aged; Case-Control Studies; Chronic Disease; Coronary Disease; Dipyridamole; Disease Progression; Endothelium, Vascular; Exercise Test; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Severity of Illness Index; Stroke Volume; Tomography, Emission-Computed; Vasodilator Agents; Ventricular Dysfunction, Left

Patients with liver cirrhosis and chronic heart failure (CHF) have a reduced capacity to excrete water. Studies in healthy humans have shown that an acute water load reduces the excretion of aquaporin-2 in urine (u-AQP-2). We wanted to test the hypothesis that an acute water load reduces u-AQP-2 less in patients with liver cirrhosis or CHF than in healthy humans.. Fourteen healthy subjects, 14 patients with liver cirrhosis, and 14 patients with CHF were given an oral water load of 20 mL/kg. Urine was collected every 30 minutes for 4 hours for analysis of u-AQP-2. Blood samples were drawn at the beginning and at the end of the study for analysis of arginine vasopressin (AVP). u-AQP-2 was determined by radioimmunoassay.. During the study period, urinary output was 22.8% higher than water intake in the healthy controls and increased 14-fold from baseline, but in patients with liver cirrhosis and CHF urinary output was 14% and 24% less than the intake, while urinary output increased 7- and 19-fold from baseline, respectively. u-AQP2 decreased significantly more in patients with CHF (39%) than in healthy controls (17%) but it was unchanged in those with liver cirrhosis. AVP decreased 46% in patients with CHF, but was unchanged in healthy controls and those with liver cirrhosis. A 24-hour urinary excretion of AQP-2 was significantly elevated in patients with CHF (median, 25.7 nmol/mol creatinine) compared to healthy controls (15.7 nmol/mol creatinine) and those with liver cirrhosis (17 nmol/mol creatinine).. The excretion of AQP-2 in urine is abnormal both in liver cirrhosis in which we find less suppression of u-AQP2 by an acute water load and in CHF in which we find a high baseline level and an exaggerated suppression of u-AQP2 by an acute water load.

Topics: Adult; Aldosterone; Angiotensin II; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin; Atrial Natriuretic Factor; Chronic Disease; Drinking; Female; Heart Failure; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Osmolar Concentration; Renin; Urine; Water-Electrolyte Balance

To determine if B-type natriuretic peptide (BNP) measurement could be useful in determination of functional capacity in patients suffering from chronic heart failure.. Evaluating functional capacity is a crucial factor in the follow-up of patients with chronic heart failure. There are numerous methods for measuring functional capacity and their relative merits remain under discussion. Clinical classifications are very subjective and other methods are difficult to use in clinical practice.. We evaluated functional capacity in 151 consecutive patients using the 6-min walk test. All patients were clinically classified using the New York Heart Association (NYHA) classification. We measured BNP plasma levels using a bedside BNP test.. Six minute walk test performance decreased through NYHA classes 1 to 4 (469+/-87, 411+/-82, 325+/-83 and 196+/-63 m, respectively, P<0.01) and BNP levels increased through NYHA classes 1 to 4 (26.3+/-7.2, 73+/-13, 401+/-74 and 924+/-84 pg/ml, respectively, P<0.001). There was a significant correlation between 6-min walk test performance and BNP plasma levels (R=0.69 P<0.001) and a weaker correlation between BNP and left ventricular ejection fraction (R=0.45 P<0.04). In some patients there was a mismatch between NYHA classification and 6-min walk test performance. In all cases BNP could correct the clinical estimation of functional capacity. When we divided the patients into three sub-groups within each NYHA class, we showed that using BNP could better define functional capacity in patients suffering from chronic heart failure in NYHA classes I to III.. The measurement of BNP levels thus usefully supplements the clinical examination. The existence of bedside BNP testing methods facilitates its use in routine clinical practice. It also permits easier follow-up of patients with chronic heart failure.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Follow-Up Studies; France; Furosemide; Heart Failure; Humans; Incidence; Lisinopril; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Severity of Illness Index; Spironolactone; Stroke Volume; Treatment Outcome

Clinical results of the Maze procedure for treatment of atrial fibrillation (AF) are excellent, suggesting improved ventricular function after restoring sinus rhythm. However, long-term corresponding effects on the release of cardiac natriuretic peptides and other vasoactive hormones are incompletely investigated after isolated Maze surgery.. Plasma levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), antidiuretic hormone, aldosterone, and angiotensin II were measured in 15 patients (mean age, 52 +/- 11 years) undergoing isolated surgical Maze (III) procedures for medically refractory AF, preoperatively and 6 months postoperatively. At the time of blood sampling, hemodynamic correlates were obtained at baseline and after 6 and 12 minutes of rapid ventricular pacing at 150 stimulations/minute.. All patients were free of AF at 6-month follow-up. The measured plasma levels of BNP, ANP, and angiotensin II were all significantly lower (p = 0.03) late after the isolated Maze procedure. Cardiac output was significantly higher postoperatively (p < 0.01). Other hemodynamic values and left atrial size were unchanged after surgery. Ventricular pacing caused almost identical hemodynamic changes in atrial pressures before and late after surgery, but the associated plasma ANP response was significantly attenuated postoperatively (p < 0.001).. Levels of cardiac natriuretic peptides and angiotensin II as markers of ventricular function are improved in the long term after clinically successful isolated Maze procedures. ANP response to hemodynamic challenge by ventricular pacing was attenuated postoperatively, possibly due to atrial scarring.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Cryosurgery; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Postoperative Complications; Vasopressins; Ventricular Dysfunction, Left; Ventricular Function, Left

The impaired ability to excrete sodium is a key feature of established congestive heart failure and is also apparent in asymptomatic left ventricular (LV) impairment. However, few studies have examined responses to chronic volume loading immediately post-myocardial infarction (MI). Experimental MI was induced in six sheep by thrombogenic coil coronary artery occlusion, and resulted in significant LV dysfunction with reduced LV ejection fraction ( P =0.001) and subsequent remodelling (increased LV volumes, P =0.015). Chronic volume loading with 2, 3 and 4 litres/day intravenous saline (each for 7 days) showed no evidence of renal sodium or volume retention in sheep with experimental MI compared with six normal control sheep. Plasma levels of brain natriuretic peptide (BNP), N-terminal pro-BNP and cGMP (all P <0.05) were higher in the MI group compared with normal control sheep. There were no differences in haemodynamics, body mass or renin-aldosterone levels between groups. This study provides evidence that natriuretic peptides play a pivotal role in preserving volume/electrolyte balance in the early stages of post-MI cardiac dysfunction.

Topics: Animals; Chronic Disease; Cyclic GMP; Female; Homeostasis; Models, Animal; Myocardial Infarction; Natriuretic Peptide, Brain; Sheep; Sodium; Sodium Chloride; Ventricular Dysfunction, Left

Topics: Biomarkers; Cardiac Output, Low; Chronic Disease; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Statistics, Nonparametric; Ventricular Dysfunction, Left

Previous reports indicate that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) increase in atrial fibrillation (AF), but decrease after successful direct current (DC) cardioversion. Although the maze procedure is the only curative therapy for AF, the effects on atrial and left ventricular function remain unclear. The study aim was to determine whether plasma ANP and BNP levels decrease after the maze procedure in patients with mitral valve disease.. Twenty-seven patients either with (n = 23) or without (n = 4) AF underwent mitral valve surgery; of these patients, 13 underwent a maze procedure for chronic AF. Blood samples and echocardiographic data were obtained before and at one year after surgery.. Ten patients with AF achieved sinus rhythm (SR) or junctional rhythm after the maze procedure. In patients subjected to mitral valve surgery, mean plasma levels of ANP and BNP were 59.8 +/- 11.9 and 139.2 +/- 53.7 pg/ml, respectively. ANP and BNP plasma levels fell significantly after surgery (to 32.1 +/- 4.1 and 46.7 +/- 10.2 pg/ml, respectively; p = 0.04 and p = 0.004). In patients with successful maze procedure, plasma levels of BNP and left ventricular end-diastolic dimension (LVDd) were significantly decreased by 35.7% and 82.7% compared with preoperative values (BNP, 35.7 +/- 4.9% for SR versus 83.4 +/- 9.6% for AF, p = 0.008; LVDd, 82.7 +/- 3.7% for SR versus 97.0 +/- 3.2% for AF, p = 0.0159).. A successful maze procedure significantly decreased LVDd and plasma levels of BNP after surgery. These results show that the maze procedure is effective in improving left ventricular diastolic dysfunction for a mid-term period in patients with mitral valve disease.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cohort Studies; Electric Countershock; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Probability; Prognosis; Regression Analysis; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes.. The present study evaluated 238 patients with advanced HF referred for cardiac transplantation evaluation who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from analysis. cTnI was detectable (cTnI > or =0.04 ng/mL) in serum of 117 patients (49.1%). Patients with detectable cTnI levels had significantly higher B-type natriuretic peptide (BNP) levels (P<0.001) and more impaired hemodynamic profiles, including higher pulmonary wedge pressures (P=0.002) and lower cardiac indexes (P<0.0001). A significant correlation was found between detectable cTnI and progressive decline in ejection fraction over time. Furthermore, detectable cTnI was associated with increased mortality risk (RR, 2.05; 95% CI, 1.22 to 3.43). After adjustment for other factors associated with adverse prognosis including age, sex, ejection fraction, and coronary artery disease, cTnI remained a significant predictor of death. cTnI used in conjunction with BNP further improved prognostic value.. cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.

Topics: Academic Medical Centers; Atrial Natriuretic Factor; California; Chronic Disease; Cohort Studies; Comorbidity; Disease Progression; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Survival Rate; Troponin I; Ventricular Dysfunction

Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE inhibitors. In cardiomyocyte/endothelial cell cocultures, bradykinin efficacy is abolished by high-glucose-induced endothelial NO dysfunction. We now demonstrate that antihypertrophic actions of natriuretic peptides, which stimulate cyclic GMP independently of NO, are preserved in cardiomyocytes despite high-glucose-induced endothelial dysfunction. Further, streptozotocin-induced diabetes significantly impairs the effectiveness of acute antihypertrophic strategies in isolated rat hearts. In hearts from citrate-treated control rats, angiotensin II-stimulated [(3)H]phenylalanine incorporation and atrial natriuretic peptide and beta-myosin heavy chain mRNA expression were prevented by B-type natriuretic peptide (BNP), bradykinin, the ACE inhibitor ramiprilat, and the neutral endopeptidase inhibitor candoxatrilat. These antihypertrophic effects were accompanied by increased left ventricular cyclic GMP. In age-matched diabetic hearts, the antihypertrophic and cyclic GMP stimulatory actions of bradykinin, ramiprilat, and candoxatrilat were absent. However, the blunting of hypertrophic markers and accompanying increases in cyclic GMP stimulated by BNP were preserved in diabetes. Thus BNP, which increases cyclic GMP independently of NO, is an important approach to prevent growth in the diabetic myocardium, where endothelium-dependent mechanisms are compromised.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Cardiomegaly; Cells, Cultured; Chronic Disease; Cyclic GMP; Diabetes Mellitus, Experimental; Gene Expression; Heart Ventricles; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phenylalanine; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tritium

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Chronic Disease; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and patients with chronic heart failure (CHF) are reported to have high plasma ET-1 levels. The aim of this study was to investigate the relation between plasma ET-1 levels and clinical correlates in patients with CHF. The effects of maximal exercise on plasma ET-1 levels were also investigated.. Plasma concentrations of ET-1, norepinephrine, and atrial and brain natriuretic peptide (ANP and BNP) both at rest and after maximal cardiopulmonary exercise test were determined in 100 patients with CHF (60 +/- 12 years, New York Heart Association [NYHA] class I-III, left ventricular ejection fraction [LVEF]=36 +/- 8%, peak oxygen uptake [VO2] = 18.2 +/- 5.0 mL/min/kg) and 27 controls.. Patients with NYHA class II and III CHF had higher ET-1 levels (controls, NYHA class I, II, III: 2.1 +/- 0.6, 2.1 +/- 1.0, 2.6 +/- 0.9, 3.4 +/- 0.8 pg/mL, analysis of variance P <.0001). Maximal exercise did not alter ET-1 levels in controls or in each CHF subgroup. When all CHF patients were analyzed together, cardiothoracic ratio (P<.01), peak VO2 (P<.001), plasma norepinephrine (P<.01), plasma ANP (P<.01), and plasma BNP (P<.001) were significantly related with resting ET-1 levels on univariate analysis. Multivariate analysis revealed peak VO2 and plasma BNP levels showed an independent and significant relationship with the resting plasma ET-1 levels.. Resting ET-1 levels were increased in symptomatic patients with CHF, and maximal exercise did not increase ET-1 levels. Peak VO2 and plasma BNP levels were independently associated with resting plasma ET-1 levels in patients with CHF.

Topics: Aged; Anaerobic Threshold; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Endothelin-1; Exercise; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Norepinephrine; Severity of Illness Index; Statistics as Topic; Systole; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) levels were measured in 72 outpatients with chronic atrial fibrillation (AF) and in 49 control patients without AF. BNP levels were significantly higher in patients with AF (median value 131 pg/ml) than without AF (median value 49 pg/ml; p <0.001), and remained significantly higher after controlling for demographic and clinical variables.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Demography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Severity of Illness Index

Cyclic GMP (cGMP) serves as an intracellular second messenger of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and nitric oxide (NO) and its peripheral blood concentration is an index of its biological activity. It has been reported that the plasma concentration of cGMP is correlated with the concentrations of ANP and BNP and is related to the prognosis of chronic heart failure patients, but the relation with NO has not been studied. Therefore, we investigated the roles of ANP, BNP, and NO in relation to cGMP in the blood during worsening and improvement of chronic heart failure. The subjects were 25 patients who were hospitalized in our hospital for acute worsening of chronic heart failure. Plasma concentrations of NO, norepinephrine (NE), ANP, BNP, and cGMP were measured on acute worsening (admission) and improvement (discharge) of heart failure. The cGMP concentration on worsening showed a positive correlation with the NO concentration (r = (0.57, P < 0.01), but no correlations with ANP or BNP were observed. The cGMP concentration on improvement showed no correlation with the NO concentration, but a positive correlation with ANP (r = 0.69, P < 0.001) and BNP (r = 0.67, P < 0.001). No correlation was observed between the NO and NE concentrations. We also studied serious cases of NYHA IV and mild cases of NYHA II to III. The cGMP concentration in the serious group showed a positive correlation with the NO concentration but no correlations with ANP or BNP concentrations on worsening. However, in the mild group, the cGMP concentration during worsening showed positive correlations with both the NO and BNP concentrations. On improvement, the cGMP concentration showed no correlation with the NO concentration but positive correlations with both the ANP and BNP concentrations in both the severe and mild groups. The results suggest the possibility that cGMP is produced mainly by NO during worsening, and by ANP and BNP rather than NO during improvement of chronic heart failure.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Nitric Oxide; Norepinephrine; Tropanes

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.

Topics: Atrial Natriuretic Factor; Chronic Disease; Cytokines; Exercise Test; Female; Heart Failure; Humans; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Oxygen Consumption; Renin-Angiotensin System; Tumor Necrosis Factor-alpha

Recent studies have suggested that cardiac troponin T (cTnT) and troponin I may detect ongoing myocardial damage involved in the progression of chronic heart failure (CHF). This study was prospectively designed to examine whether the combination of cTnT, a marker for ongoing myocardial damage, and B-type natriuretic peptide (BNP), a marker for left ventricular overload, would effectively stratify patients with CHF after initiation of treatment.. We measured serum cTnT, plasma BNP, and left ventricular ejection fraction (LVEF) on admission for worsening CHF [New York Heart Association (NYHA) functional class III to IV] and 2 months after initiation of treatment to stabilize CHF (n = 100; mean age, 68 years).. Mean (SD) concentrations of cTnT [0.023 (0.066) vs 0.063 (0.20) micro g/L] and BNP [249 (276) vs 753 (598) ng/L], percentage increased cTnT (>0.01 micro g/L; 35% vs 60%), NYHA functional class [2.5 (0.6) vs 3.5 (5)], and LVEF [43 (13)% vs 36 (12)%] were significantly (P <0.01) improved 2 months after treatment compared with admission. During a mean follow-up of 391 days, there were 44 cardiac events, including 12 cardiac deaths and 32 readmissions for worsening CHF. On a stepwise Cox regression analysis, increased cTnT and BNP were independent predictors of cardiac events (P <0.001). cTnT >0.01 micro g/L and/or BNP >160 ng/L 2 months after initiation of treatment were associated with increased cardiac mortality and morbidity rates.. The combination of cTnT and BNP measurements after initiation of treatment may be highly effective for risk stratification in patients with CHF.

Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Patient Readmission; Predictive Value of Tests; Prospective Studies; Risk Assessment; Troponin T; Ventricular Function, Left

The diagnostic and prognostic values of plasma B-type natriuretic peptide (BNP) testing are established. However, the range of plasma BNP levels present in the setting of chronic, stable systolic heart failure (HF) is unclear.. We followed up 558 consecutive ambulatory patients with chronic, stable systolic HF (left ventricular ejection fraction <50%) treated at a specialized outpatient HF clinic between November 2001 and February 2003. Retrospective chart review was performed to determine clinical and functional data at the time of BNP testing (Biosite Triage). The clinical characteristics of patients with plasma BNP levels <100 pg/mL and those with > or =100 pg/mL were compared. In our cohort, 60 patients were considered asymptomatic, and their plasma BNP levels ranged from 5 to 572 pg/mL (median, 147 pg/mL). Of the remaining 498 symptomatic (NYHA functional class II-III) patients, 106 (21.3%) had plasma BNP levels in the "normal" diagnostic range (<100 pg/mL). Patients in this "normal BNP" subgroup were more likely to be younger, to be female, to have nonischemic pathogenesis, and to have better-preserved cardiac and renal function and less likely to have atrial fibrillation.. In the ambulatory care setting, both symptomatic and asymptomatic patients with chronic, stable systolic HF may present with a wide range of plasma BNP levels. In a subset of symptomatic patients (up to 21% in our cohort), plasma BNP levels are below what would be considered "diagnostic" (<100 pg/mL).

Topics: Cardiac Output, Low; Chronic Disease; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Retrospective Studies; Systole

Topics: Cardiac Output, Low; Chronic Disease; Humans; Natriuretic Peptide, Brain; Treatment Outcome

To examine retrospectively the changes in ECG parameters over time and their correlation with other quantitative right ventricular (RV) function parameters in patients with chronic RV pressure overload caused by congenital heart disease.. 48 patients with chronic RV pressure overload caused by the following congenital heart diseases were studied: nine with congenitally corrected transposition of the great arteries (TGA), 12 with surgically corrected TGA, and 27 with a subpulmonary pressure overloaded RV. QRS duration and dispersion were measured manually from standard ECG recorded twice within five years. RV end diastolic volume (EDV) and RV mass were determined by magnetic resonance imaging. Brain natriuretic peptide (BNP) plasma concentrations were measured.. QRS duration and QRS dispersion increased in all patient groups during the follow up period. QRS duration increased significantly in the congenitally corrected TGA (p = 0.04) and the subpulmonary pressure overloaded RV groups (p = 0.01). QRS dispersion increased significantly in patients with surgically corrected TGA (p = 0.03) and in the subpulmonary pressure overloaded RV group (p = 0.02). A significant correlation was found between QRS duration and RVEDV (r = 0.71, p < 0.0001). RV mass was significantly correlated with QRS duration in patients with tetralogy of Fallot (r = 0.67, p = 0.01). Mean (SD) plasma brain natriuretic peptide concentrations (6.6 (5.4) pmol/l) were increased compared with normal reference values but no correlation was found with ECG parameters or RV systolic pressure. No malignant arrhythmia or sudden death occurred.. ECG parameters worsened gradually in asymptomatic or minimally symptomatic patients with chronic RV pressure overload, regardless of the nature of their congenital heart disease. In all patients, a significant positive correlation was found between QRS duration and RVEDV. In patients with tetralogy of Fallot there was also a correlation between QRS duration and RV mass.

Topics: Adult; Blood Pressure; Chronic Disease; Electrocardiography; Female; Heart Defects, Congenital; Humans; Magnetic Resonance Angiography; Male; Natriuretic Peptide, Brain; Retrospective Studies; Tachycardia, Supraventricular; Tachycardia, Ventricular; Transposition of Great Vessels; Ventricular Dysfunction, Right

The goal of this study was to determine if brain natriuretic peptide (BNP) levels are associated with exercise capacity in patients with chronic heart failure (HF).. Plasma levels of BNP are increased subject to the degree of systolic and diastolic left ventricular dysfunction in patients with chronic HF. Exercise testing is useful to assess functional capacity and prognosis in chronic HF.. We prospectively studied 70 consecutive patients with chronic HF (60.3 +/- 10.4 years, 51 men) referred for cardiopulmonary exercise testing. Resting BNP was obtained after 10 min of supine rest before symptom-limited bicycle exercise testing.. In patients with chronic HF, BNP levels correlated with oxygen uptake (VO(2)), both at anaerobic threshold (VO(2)AT: r = -0.54, p < 0.001) and peak exercise (peak VO(2): r = -0.56, p < 0.001). Impairment of ventilatory efficiency (EqCO(2): r = 0.43, p < 0.001) and maximum exercise level (W % predicted: r = -0.44, p < 0.05) correlated less well with BNP. There was a significant inverse correlation between left ventricular ejection fraction and BNP (r = -0.50, p < 0.05). Brain natriuretic peptide discriminated well chronic HF patients with a peak VO(2) <10 ml/min/kg (area under the receiver operating characteristic [ROC] 0.93) or <14 ml/min/kg (area under the ROC 0.72). A BNP >316 pg/ml was associated with a risk ratio of 6.8 (95% confidence interval, 2.3 to 19.8) for a reduced exercise capacity with a peak VO(2) <14 ml/min/kg.. Brain natriuretic peptide is clearly associated with exercise capacity in chronic HF. Brain natriuretic peptide levels show a significant correlation with the impairment of VO(2) at peak exercise and anaerobic threshold. Brain natriuretic peptide is able to differentiate between chronic HF patients with moderately and severely impaired exercise capacity.

Topics: Chronic Disease; Exercise Test; Exercise Tolerance; Heart Failure; Humans; Natriuretic Peptide, Brain; ROC Curve

Brain natriuretic peptide (BNP) levels have been used to assess clinical status and predict prognosis of patients with chronic heart failure (CHF). However, BNP levels can only be measured in specialized laboratories which has hampered its use in daily clinical practice. We compared a new, rapid, BNP assay with a conventional BNP measurement and evaluated the applicability to current practice by comparing it with standard clinical parameters.. BNP levels were determined in 78 stable CHF patients and 20 controls. The severity of CHF was assessed by determination of New York Heart Association functional class (NYHA), left ventricular ejection fraction (LVEF) and peak oxygen consumption (peak VO(2)), and these parameters were compared to BNP levels.. Overall, rapid BNP assessment was highly correlated with the conventional BNP assay (r=0.95, P<0.0001). In the higher ranges (>200 pmol/l), however, correlation was less accurate, and tended to overestimate. BNP levels also strongly correlated with both NYHA class, LVEF and peak VO(2) (all P<0.001). A cut-off value for BNP of 20 pmol/l yielded a sensitivity of 91% and a specificity of 92% to detect the presence of left ventricular systolic dysfunction.. Rapid measurement of BNP levels is comparable to conventional BNP measurement and strongly correlated to clinical tests that are currently used to stratify CHF patients. Wider use of this method may yield a reduction of costly and time-consuming clinical tests and may reduce the medical burden of CHF.

Topics: Adult; Aged; Chronic Disease; Echocardiography; Female; Fluoroimmunoassay; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Point-of-Care Systems; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Time Factors; Ventricular Function, Left

We prospectively evaluated whether the combination of admission measurements of a marker for myocardial cell injury and a marker for left ventricular overload would effectively risk stratify patients with acutely decompensated heart failure. We measured serum concentrations of cardiac troponin T (cTnT) using a second-generation assay, as well as serum cardiac troponin I (cTnI) and plasma atrial and brain natriuretic peptide (BNP) concentrations on admission in 98 consecutive patients hospitalized for worsening chronic heart failure (mean age 69 years; 5 patients were in New York Heart Association functional class II, 35 were in class III, and 58 patients were in class IV). During a mean follow-up period of 451 days, there were 37 cardiac events, including 21 cardiac deaths (14 in-hospital deaths) and 16 readmissions for worsening heart failure. In a stepwise Cox regression analysis, including these biochemical markers, age, sex, functional class, and left ventricular ejection fraction, cTnT, and BNP were found to be significantly independent predictors of both cardiac death (p <0.05) and cardiac events (p <0.01). A cTnT >0.033 microg/L and/or a BNP >440 pg/ml on admission was correlated with an incremental increase in in-hospital cardiac mortality, overall cardiac mortality, and cardiac event rate. Kaplan-Meier analysis revealed that this combination could reliably stratify the patients into low-, intermediate-, and high-risk groups for cardiac events. Measuring the combination of admission concentrations of cTnT and BNP may be a highly effective means of risk stratification of patients hospitalized for worsening chronic heart failure.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Time Factors; Troponin I; Troponin T

The aim of this study was to evaluate the relationship between plasma oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, and the prognosis of patients with chronic congestive heart failure (CHF).. Oxidative stress appears to play a role in the pathophysiology of CHF. We have recently reported the usefulness of plasma oxLDL as a marker of oxidative stress in CHF patients with dilated cardiomyopathy.. We measured the plasma level of oxLDL by sandwich enzyme-linked immunosorbent assay using a specific monoclonal antibody against oxLDL in 18 age-matched normal subjects and in 84 patients with chronic CHF (New York Heart Association functional class II to IV) and monitored them prospectively for a mean follow-up period of 780 days.. Plasma oxLDL level was significantly higher in severe CHF patients than in control subjects and mild CHF patients. A significant negative correlation existed between the plasma level of oxLDL and left ventricular ejection fraction (LVEF) and a significant positive correlation between the plasma level of oxLDL and plasma norepinephrine level. Twenty-six patients had cardiac events; 14 had cardiac death and 12 were hospitalized for heart failure or other cardiovascular events. Among 10 variables including LVEF and neurohumoral factors, only high plasma levels of brain natriuretic peptide and oxLDL were shown to be independent predictors of mortality.. These results indicate that the plasma level of oxLDL is a useful predictor of mortality in patients with CHF, suggesting that oxidative stress plays an important role in the pathophysiology of CHF.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Lipoproteins, LDL; Male; Middle Aged; Morbidity; Natriuretic Peptide, Brain; Norepinephrine; Oxidative Stress; Predictive Value of Tests; Prognosis; Severity of Illness Index; Stroke Volume; Survival Analysis

Given the high incidence of sudden death in patients with chronic heart failure (CHF) and the efficacy of implantable cardioverter-defibrillators, an appropriate tool for the prediction of sudden death is desirable. B-type natriuretic peptide (BNP) has prognostic significance in CHF, and the stimuli for its production cause electrophysiological abnormalities. This study tests BNP levels as a predictor of sudden death.. BNP levels, in addition to other neurohormonal, clinical, and hemodynamic variables, were obtained from 452 patients with a left ventricular ejection fraction (LVEF) < or =35%. For prediction of sudden death, only survivors without heart transplantation (HTx) or a mechanical assist device and patients who died suddenly were analyzed. Up to 3 years, 293 patients survived without HTx or a mechanical assist device, 89 patients died, and 65 patients underwent HTx. Mode of death was sudden in 44 patients (49%), whereas 31 patients (35%) had pump failure and 14 patients (16%) died from other causes. Univariate risk factors of sudden death were log BNP (P=0.0006), log N-terminal atrial natriuretic peptide (P=0.003), LVEF (P=0.005), log N-terminal BNP (P=0.006), systolic blood pressure (P=0.01), big endothelin (P=0.03), and NYHA class (P=0.04). In the multivariate model, log BNP level was the only independent predictor of sudden death (P=0.0006). Using a cutoff point of log BNP <2.11 (130 pg/mL), Kaplan-Meier sudden death-free survival rates were significantly higher in patients below (99%) compared with patients above (81%) this cutoff point (P=0.0001).. BNP levels are a strong, independent predictor of sudden death in patients with CHF.

Topics: Adrenergic beta-Antagonists; Alprostadil; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Chronic Disease; Comorbidity; Death, Sudden, Cardiac; Endothelin-1; Endothelins; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Factors; Stroke Volume; Survival Analysis; Treatment Outcome

We sought to assess the effects of brain natriuretic peptide (BNP) on systemic and regional sympathetic nervous activity (SNA) in both patients with congestive heart failure (CHF) and healthy control subjects.. Although the response of SNA to atrial natriuretic peptide (ANP) has been well documented, the response of SNA to BNP is largely unknown.. We assessed cardiac and whole-body SNA using the norepinephrine (NE) tracer dilution method before and after infusion of two doses of BNP (3 and 15 ng/kg body weight per min) in 11 patients with stable CHF (ejection fraction 24 +/- 2%) and 12 age-matched healthy control subjects. In addition, renal SNA and hemodynamic variables were assessed at baseline and after the higher BNP dose.. Low dose BNP did not change blood pressure or whole-body NE spillover, but reduced cardiac NE spillover in both groups by 32 +/- 13 pmol/min (p < 0.05). In both groups, high dose BNP reduced pulmonary capillary pressure by 5 +/- 1 mm Hg (p < 0.001) and mean arterial pressure by 6 +/- 3 mm Hg (p < 0.05), without a concomitant increase in whole-body NE spillover; however, cardiac NE spillover returned to baseline levels. Renal NE spillover remained virtually unchanged in healthy control subjects (501 +/- 120 to 564 +/- 115 pmol/min), but was reduced in patients with CHF (976 +/- 133 to 656 +/- 127 pmol/min, p < 0.01).. Our results demonstrate a sympathoinhibitory effect of BNP. Cardiac sympathetic inhibition was observed at BNP concentrations within the physiologic range, whereas high dose BNP, when arterial and filling pressures fell and reflex sympathetic stimulation was expected, systemic and cardiac SNA equated to baseline values. There was inhibition of renal SNA in patients with CHF, but not in healthy control subjects. Whether this effect is specific to BNP or related to reduced filling pressure remains to be determined.

Topics: Chronic Disease; Dose-Response Relationship, Drug; Female; Heart; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Neural Inhibition; Norepinephrine; Reference Values; Sympathetic Nervous System

According to previous reports, plasma atrial natriuretic peptide levels increase in atrial fibrillation (AF) and decrease after successful direct current (DC) cardioversion, but there have been no reports on plasma brain natriuretic peptide (BNP).. To determine whether plasma BNP levels decrease after successful direct DC cardioversion in patients with chronic AF.. Twenty patients who remained in sinus rhythm for at least seven days after cardioversion, and 20 normal control subjects, were studied. Group A consisted of 10 patients with underlying heart disease, including dilated cardiomyopathy (n=2), hypertrophic cardiomyopathy (n=1), mitral valve disease (n=3), hypertensive heart disease (n=3) and status after atrial septal closure (n=1). Group B consisted of 10 patients with just AF. Group C (serving as controls) comprised 20 subjects with normal sinus rhythm and no risk factors.. Before cardioversion, plasma BNP levels were higher in group A (176.7+/-128.1 ng/mL) and in group B (96.8+/-51.7 ng/ml) than in group C (6.3+/-3.8 ng/ml) (P<0.01 for all). After successful cardioversion, mean plasma BNP levels in groups A and B decreased from 136.8+/-105.5 ng/mL to 46.4+/-44.2 ng/mL (P<0.01). In group A, plasma BNP levels decreased from 176.7+/-128.1 ng/mL to 62.5+/-54.6 ng/mL (P<0.01), and in group B, plasma BNP levels decreased from 96.8+/-51.7 ng/mL to 30.3+/-23.8 ng/mL (P<0.01).. Lone AF raises plasma BNP levels, which is more marked if there is underlying structural heart disease present, and cardioversion reduces plasma BNP levels. Therefore, high plasma BNP levels in patients with chronic AF are likely to be caused by AF and reflect cardiac overloading associated with, although contributed to in part by, underlying heart diseases.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Electric Countershock; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography

The objective was to determine the independent association between atrial fibrillation (A-Fib) and activation of natriuretic peptides.. The association of A-Fib with activation of N-terminal atrial and brain natriuretic peptides (N-ANPs and BNPs, respectively) is uncertain but of great importance for the diagnostic utilization of natriuretic peptides. This uncertainty is related to the lack of appropriate controls, with left ventricular (LV) and atrial overload similar to A-Fib.. We prospectively measured N-terminal atrial and BNPs and endothelin-1 levels in 100 patients and 14 age- and gender-matched control subjects. The 32 patients with A-Fib were compared with 68 patients in sinus rhythm and similar LV and atrial overload (due to mitral regurgitation or LV dysfunction) measured simultaneously with hormonal levels with comprehensive Doppler echocardiography.. Patients with A-Fib compared with those in sinus rhythm had similar symptoms, comorbid conditions, cardioactive medications, pulmonary pressure, left atrial volume, and LV ejection fraction and filling characteristics but demonstrated higher N-ANP levels (2,613 +/- 1,681 vs. 1,654 +/- 1,323 pg/ml, p = 0.007) even after adjustment for the underlying cardiac disease (p < 0.0001). Conversely, BNP levels were similar in both groups (165 +/- 163 vs. 160 +/- 269 pg/ml, p = 0.9). In multivariate analysis, a higher N-ANP level was associated with A-Fib (p = 0.0003), symptom class (p < 0.0001) and endothelin-1 level (p = 0.032) independently of left atrial volume and LV ejection fraction. Conversely, BNP showed no independent association with and was most strongly associated with LV ejection fraction (p < 0.0001).. Atrial fibrillation is an independent determinant of higher N-ANP levels and blurs its association with LV dysfunction. Conversely, the BNP is not independently associated with A-Fib and is strongly determined by LV dysfunction, for which it is an independent marker.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Chronic Disease; Echocardiography, Doppler; Endothelin-1; Female; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; Reproducibility of Results; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

The purpose of this study was to evaluate whether the plasma brain natriuretic peptide (BNP) concentration is a useful marker of right ventricular (RV) overload and whether it has prognostic value as a predictor of death in patients with chronic respiratory disease (CRD). We measured the plasma BNP and atrial natriuretic peptide (ANP) concentrations in 31 consecutive patients with CRD who underwent right-heart catheterization to evaluate pulmonary hypertension. All patients were followed for >12 months. The plasma BNP concentration closely correlated with the mean pulmonary artery pressure and pulmonary vascular resistance (r=0.62, P<0.0005 and r=0. 85, P<0.0001), and showed a weak linear correlation with cardiac output (r=-0.36, P<0.05). During the follow-up period, 5 (16%) end-stage CRD deaths (4 RV heart failure and 1 respiratory infection) and 2 non-end-stage CRD deaths occurred. In a stepwise multivariate Cox proportional-hazards regression analysis including age, sex, BNP, ANP, hemodynamic variables and the ratio of PaO(2) to fraction of inspired oxygen, only BNP (P<0.05) was an independent predictor of end-stage CRD death. The upward and leftward shift in the receiver operating characteristic curve between patients with end-stage CRD death and those without was greater for BNP than for ANP. Our findings suggest that the plasma BNP concentration may be an inexpensive, simple and useful marker of RV overload and end-stage CRD death in CRD patients. These preliminary results need to be confirmed in a large series of CRD patients.

Topics: Aged; Chronic Disease; Female; Heart Ventricles; Humans; Lung Diseases; Male; Middle Aged; Natriuretic Peptide, Brain

The aim of this study was to evaluate whether repetitive measurements of plasma levels of neurohumoral factors and cytokines before and after additional treatment are useful for predicting mortality in patients with congestive heart failure (CHF).. Neurohumoral and immune activation play an important role in the pathophysiology of CHF. However, the effects of serial changes in these factors on the prognostic value remain unknown.. We measured plasma levels of neurohumoral factors and cytokines and left ventricular ejection fraction (LVEF) before and three months after optimized treatment for CHF in 102 consecutive patients with severe CHF (New York Heart Association class III to IV) on admission to our hospital. Physicians who were blind to the plasma neurohumoral factors until study completion treated patients using standard drugs. Patients were monitored for a mean follow-up period of 807 days.. Plasma levels of neurohumoral factors, cytokines and LVEF were significantly improved three months after optimized treatment. Cardiac death occurred in 26 patients. Among 19 variables including LVEF, only a high level of brain natriuretic peptide (BNP) and interleukin-6 (IL-6) at three months after optimized treatment showed significant independent relationships by Cox proportional hazard analysis with a high mortality for patients with CHF.. These findings indicate that high plasma BNP and IL-6 levels three months after optimized treatment are independent risk factors for mortality in patients with CHF, suggesting that sustained high plasma levels of BNP and IL-6 after additional standard treatment were independent risk factors for mortality in patients with CHF despite improvements in LVEF and symptoms.

Topics: Aged; Biological Factors; Chronic Disease; Cytokines; Female; Heart Failure; Humans; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; Stroke Volume

Chronic atrial fibrillation (AF) is one of the main complications of sick sinus syndrome (SSS). As previously reported, plasma brain natriuretic peptide (BNP), reflects hemodynamic changes in different pacing modes, as does plasma atrial natriuretic peptide (ANP), so the present study investigated whether plasma BNP or ANP can predict chronic AF after single-chamber ventricular (VVI) pacemaker implantation in patients with SSS. Plasma ANP and BNP levels were measured before and 1-3 months after implantation in 99 SSS patients. Long-term follow-up was conducted with chronic AF as an endpoint. Chronic AF occurred in 19 patients during a mean follow-up of 5.1 years. Plasma ANP and BNP were significantly higher in the patients who developed chronic AF after implantation than in those who did not, despite similar ANP and BNP levels between the 2 groups before implantation. Post-implant high BNP and a history of paroxysmal AF were independent predictors of chronic AF by a multivariate Cox proportional hazards analysis. Plasma BNP can predict the development of chronic AF after VVI pacemaker implantation in patients with SSS because increased levels may reflect latent hemodynamic abnormalities, which may contribute to the development of AF after VVI pacemaker implantation.

Topics: Actuarial Analysis; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Cardiac Pacing, Artificial; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Sick Sinus Syndrome; Survival Rate

This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) < 120ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 +/- 145 pg/ml and 865 +/- 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = -0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r =-0.50, P = 0.003). The combined index of both shorter DcT (< 120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (chi2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Blood Flow Velocity; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prognosis

Brain natriuretic peptide (BNP) is a recently discovered peptide, secreted by the atria and ventricles in response to parietal distension. It was recently proposed as a screening test for left ventricular failure. The authors assayed this peptide at rest in 37 patients with chronic heart failure due to left ventricular systolic dysfunction and another 20 patients with various diseases (respiratory failure, cirrhosis, heart transplantation, "diastolic" heart failure) but normal left ventricular systolic function. A significant increase compared to normal values was observed not only in the group of heart failure patients, but also in patients with all other diseases. BNP was significantly higher in NYHA class IV patients. The relationship between plasma BNP levels and ejection fraction was not significant. On the other hand, a good correlation was observed between BNP and left ventricular filling parameters evaluated by cardiac Doppler: E wave deceleration time (r = -0.53, p = 0.001), E/A ratio: r = 0.57 p = 0.005) or VO2 max (r = -0.55, p < 0.005).

Topics: Aged; Analysis of Variance; Case-Control Studies; Chronic Disease; Creatinine; Diastole; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Rest; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Systole; Ventricular Dysfunction, Left

In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Erythropoietin; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Heart Ventricles; Hemodynamics; Hypoxia; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger

Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice.. We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40).. Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group.. Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Survival Analysis; Ventricular Dysfunction, Left

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Exercise; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Stroke Volume; Ventricular Function, Left

Patients with congestive heart failure (CHF) have high plasma levels of atrial natriuretic peptide (ANP), mainly from the atrium, and brain natriuretic peptide (BNP), mainly from the ventricle. We examined the prognostic role of plasma BNP in chronic CHF patients in comparison with plasma ANP and other variables previously known to be associated with high mortality. We also evaluated the relationship between mortality and plasma cGMP, a biological marker of ANP and BNP.. The study subjects were 85 patients with chronic CHF (left ventricular ejection fraction <0.45) who were followed for 2 years. The plasma levels of ANP, BNP, cGMP, and norepinephrine increased with the severity of CHF. Among plasma levels of ANP, BNP, cGMP, and norepinephrine and clinical and hemodynamic parameters, only high levels of plasma BNP (P<.0001) and pulmonary capillary wedge pressure (P=.003) were significant independent predictors of the mortality in patients with CHF by Cox proportional hazard analysis. Although plasma levels of ANP and BNP were threefold or fivefold higher in nonsurvivors than in survivors, there was no difference in plasma cGMP level between nonsurvivors and survivors.. These findings indicate that plasma BNP is more useful than ANP for assessing the mortality in patients with chronic CHF and that the plasma levels of BNP provide prognostic information independent of other variables previously associated with a poor prognosis. Our findings also suggest that the compensatory activity of the cardiac natriuretic peptide system is attenuated as mortality increases in chronic CHF patients with high plasma levels of ANP and BNP.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prognosis; Ventricular Function, Left

In order to develop and validate an ovine model of myocardial infarction with subsequent impairement of left ventricular function, 15 instrumented sheep underwent selective microembolization of the left coronary arteries with 0.5 mL 90 microns polystyrene beads. Hemodynamics and plasma hormones were measured preembolization (baseline) and then at hours 2, 4, 6, and 12 and days 1, 2, 3, 5 and 7 postembolization. Of the 15 sheep studied, 2 (13%) died on the day of embolization from arrhythmias. In the remaining sheep, left ventricular systolic pressure and stroke work (both P < 0.001) were reduced promptly and remained below basal levels. Mean arterial pressure (P < 0.001) increased initially, then decreased to below basal levels by hour 6. Heart rate (P < 0.001) and left atrial pressure (P < 0.05) were increased while cardiac output was decreased (P < 0.05). Left ventricular ejection fraction at day 7 was reduced (38.8 +/- 3.5 vs 46.0 +/- 3.9% preembolization; P < 0.05). The cardiac enzymes creatine kinase (P < 0.001) and troponin-T (P < 0.001) were increased following microembolization and returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain natriuretic peptides (both P < 0.001) and plasma renin activity (P < 0.005) were all increased following embolization. This ovine model mimics the hemodynamic and neurohumoral features of acute myocardial infarction, resulting in left ventricular dysfunction, and should prove suitable for the study of interventions in a number of these conditions.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Chronic Disease; Creatine Kinase; Disease Models, Animal; Female; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin; Sheep; Stroke Volume; Ventricular Dysfunction, Left

Patients with chronic mitral regurgitation (MR) are often referred for surgery only after irreversible left ventricular (LV) dysfunction has developed. Our aim was to determine whether plasma brain natriuretic peptide (BNP) concentrations could serve as a marker for early LV dysfunction in this condition.. Twenty-two patients with isolated chronic MR and echocardiographic evidence of at least moderate regurgitation were studied.. Plasma BNP concentrations were significantly higher in patients than in normal volunteers (20.85 +/- 16.9 versus 3.37 +/- 0.9 pmol/l; p = 0.007). Concentrations increased with increasing severity of symptoms and were highest in those in NYHA class IV, but did not correlate with LV dimensions, fractional shortening or left atrial size. Of note, two asymptomatic patients with high BNP concentrations were referred for surgery within the 12-month follow up period due to symptom progression.. Plasma BNP concentrations are elevated in most patients with isolated chronic MR, including those who are asymptomatic with normal LV dimensions. The significance of these findings is uncertain, but they suggest that changes in ventricular physiology occur early in the disease process and before they can be detected echocardiographically. Longitudinal studies are required to determine if patients with high BNP levels have an adverse prognosis and if this can be altered by earlier surgical intervention.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Disease Progression; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Radioimmunoassay; Severity of Illness Index; Ventricular Dysfunction, Left

Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease.. We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors.. The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients.. These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Urea Nitrogen; Brain Ischemia; Cerebral Angiography; Cerebral Hemorrhage; Cholesterol; Chronic Disease; Endothelins; Female; Humans; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides; Risk Factors; Thrombomodulin; Tomography, X-Ray Computed; Vasodilator Agents

This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure.. Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulatory homeostasis.. The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2).. Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 +/- 41 to 263 +/- 143 pg/ml [mean +/- SD], p < 0.01, and from 38 +/- 23 to 405 +/- 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked increase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 +/- 144 to 448 +/- 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 +/- 4 to 20 +/- 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 +/- 4 to 48 +/- 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 +/- 1.3 and 2.0 +/- 0.9 ng/mg, respectively) were lower than those in the control group (11.7 +/- 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 +/- 0.006 ng/mg) were increased compared with those in the control group (0.013 +/- 0.006 ng/mg, p < 0.05) and in group 1 (0.011 +/- 0.006 ng/mg, p < 0.05).. Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release. However, the relatively modest change in cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressures.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Chronic Disease; Dextrans; Disease Models, Animal; Dogs; Heart Failure; Hemodynamics; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Plasma Substitutes

We measured plasma concentrations of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively) and endothelin-1 in 20 patients with chronic respiratory diseases (CRD) to establish whether these peptides are increased in patient groups with CRD (group A, PaO2 > or = 60 mm Hg; group B, PaO2 < 60 mm Hg) and whether a correlation exists between the levels of natriuretic peptides or endothelin-1, and blood gas variables. In patients receiving long-term oxygen therapy (LTOT), plasma ANP, BNP, and endothelin-1 were compared before and after LTOT. We compared the levels of plasma ANP, BNP, and endothelin-1 in the presence or absence of right heart overloading (RHO) found in the ECG. Plasma ANP and BNP levels in group B patients were higher than those in group A and control subjects, and endothelin-1 in group B patients was higher than in control subjects. Inverse correlations were found between PaO2 and levels of plasma ANP, BNP, and endothelin-1. Plasma ANP, BNP, and endothelin-1 decreased significantly 25.4 days after LTOT. In 10 patients with RHO findings in the ECG, plasma ANP and BNP levels were significantly elevated compared with those in patients without RHO. These findings show that plasma ANP, BNP, and endothelin-1 are elevated according to the degree of hypoxemia, and they suggest that decreases in plasma ANP, BNP, and endothelin-1 may be used as indexes of the improvement by LTOT, and that plasma ANP and BNP may represent markers of RHO.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Electrocardiography; Endothelins; Female; Heart; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Oxygen; Oxygen Inhalation Therapy; Proteins; Respiratory Tract Diseases