natriuretic-peptide--brain and Heart-Failure

A randomized, controlled trial of baroreflex activation therapy (BAT) in patients with heart failure and reduced ejection fraction demonstrated that BAT was safe and significantly improved patient-centered symptomatic outcomes, increasing exercise capacity, improving quality of life, decreasing n-terminal pro B-type natriuretic peptide (NT-proBNP), and improving functional class. BAT was approved by the FDA for improvement of symptoms of heart failure for patients who remain symptomatic despite treatment with guideline-directed management, are New York Heart Association Class III or Class II (with a recent history of Class III), have a left ventricular ejection fraction ≤ 35%, an NT-proBNP < 1600 pg/mL and excluding patients indicated for cardiac resynchronization therapy.

Topics: Baroreflex; Heart Failure; Humans; Natriuretic Peptide, Brain; Quality of Life; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

The purpose of this review was to synthesize the evidence on non-traditional biomarkers from proteomic and metabolomic studies that may distinguish heart failure (HF) with preserved ejection fraction (HFpEF) from heart failure with reduced ejection fraction (HFrEF) and non-HF.. Understanding the pathophysiology of HFpEF continues to be challenging. A number of inflammatory and metabolic biomarkers that have recently been suggested to be involved include C-reactive protein (CRP), interleukin-6 (IL-6), trimethylamine-N-oxide (TMAO), syndecan-1 (SDC-1), nitric oxide (NO), and tumor necrosis factor receptor-1 (TNFR-1). A systematic search was conducted using Medline, EMBASE, and Web of Science with search terms such as "HFpEF," "metabolomics," and "proteomics," and a meta-analysis was conducted. The results demonstrate significantly higher levels of TMAO, CRP, SDC-1, and IL-6 in HFpEF compared to controls without HF and significantly higher levels of TMAO and CRP in HFrEF compared to controls. The results further suggest that HFpEF might be distinguishable from HFrEF based on higher levels of IL-6 and lower levels of SDC-1 and NO. These data may reflect pathophysiological differences between HFpEF and HFrEF.

Topics: Biomarkers; C-Reactive Protein; Heart Failure; Humans; Interleukin-6; Natriuretic Peptide, Brain; Nitric Oxide; Prognosis; Proteomics; Stroke Volume; Syndecan-1

Whether an antidiabetic drug, glucagon-like peptide-1 receptor agonist (GLP-1RA), could improve the prognosis of heart failure and cardiac function remains controversial. We conducted a systematic review and meta-analysis of randomized controlled trials to explore the influence of GLP-1RAs on heart failure in patients regardless of diabetes diagnosis.. Literature in English from the PubMed, EMBASE, and Cochrane Library databases was searched from inception to July 2022. The study aim was to identify published, randomized, placebo-controlled trials testing GLP-1RAs in patients with or without diabetes. Outcomes were heart failure hospitalization, cardiac function, and structure measures.. Twenty-two randomized controlled trials involving 61,412 patients are included in the meta-analysis. Overall, compared with the placebo group, GLP-1RA treatment could not significantly decrease heart failure hospitalization in patients with a history of heart failure (hazard ratio [HR], 1.07; 95% CI, 0.91 to 1.25; P = 0.422). Six-minute walking test distances (WMD, 19.08 m; 95% CI, 4.81 to 33.36; P = 0.01), E-wave (SMD, -0.40; 95% CI, -0.60 to -0.20; P < 0.001), early diastolic to late diastolic velocities ratio (WMD, -0.10; 95% CI, -0.18 to -0.02; P = 0.01), mitral inflow E velocity to tissue Doppler e' ratio (WMD, -0.97; 95% CI, -1.54 to -0.41; P < 0.001), and E-wave deceleration time (WMD, -9.96 milliseconds; 95% CI, -18.52 to -1.41; P = 0.02) increased significantly after administration of GLP-1RAs. However, GLP-1RAs do not significantly influence N-terminal pro-B-type natriuretic peptide levels (WMD, -20.02 pg/mL; 95% CI, -53.12 to 13.08; P = 0.24), Minnesota Living with Heart Failure Questionnaire quality of life scores (WMD, -1.08; 95% CI, -3.99 to 1.84; P = 0.47), or left ventricular ejection fractions (WMD, -0.37%; 95% CI, -1.19 to 0.46; P = 0.38).. GLP-1RAs did not reduce heart failure readmissions in patients with a history of heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Thus, the prognosis of heart failure was not improved, although GLP-1RAs did significantly improve left ventricular diastolic function in patients. PROSPERO identifier: CRD42021226231.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart Failure; Humans; Hypoglycemic Agents; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Randomized Controlled Trials as Topic

Congestive heart failure (CHF) is the leading cause of morbidity and mortality in the elderly worldwide. Although many biomarkers associated with in heart failure, these are generally prognostic and identify patients with moderate and severe disease. Unfortunately, the role of biomarkers in decision making for early and advanced heart failure remains largely unexplored. Previous studies suggest the natriuretic peptides have the potential to improve the diagnosis of heart failure, but they still have significant limitations related to cut-off values. Although some promising cardiac biomarkers have emerged, comprehensive data from large cohort studies is lacking. The utility of multiple biomarkers that reflect various pathophysiologic pathways are increasingly being explored in heart failure risk stratification and to diagnose disease conditions promptly and accurately. MicroRNAs serve as mediators and/or regulators of renin-angiotensin-induced cardiac remodeling by directly targeting enzymes, receptors and signaling molecules. The role of miRNA in HF diagnosis is a promising area of research and further exploration may offer both diagnostic and prognostic applications and phenotype-specific targets. In this review, we provide insight into the classification of different biochemical and molecular markers associated with CHF, examine clinical usefulness in CHF and highlight the most clinically relevant.

Topics: Biomarkers; Heart Failure; Humans; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Thyroid hormones (THs) significantly affect the cardiovascular system. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker for diagnosing, evaluating, and predicting outcomes in heart failure (HF). This comprehensive review and meta-analysis aimed to investigate the effects of thyroid dysfunction (hypothyroidism and hyperthyroidism) on NT-proBNP levels.. Two investigators independently searched PubMed, Embase, Cochrane Library, and Web of Science databases for studies published from inception to July 31, 2022, without any restrictions on language.. 21 studies were included. In participants without HF, NT-proBNP levels may be elevated in those with overt hyperthyroidism (standardized mean difference [SMD] 2.38, 95% confidence interval [CI]:1.0-3.76). Notably, among patients with preexisting HF, significantly higher NT-proBNP levels were found in patients with overt hyperthyroidism, overt hypothyroidism, or subclinical hypothyroidism than in euthyroid subjects (SMD [95%CI] = 0.31[0.01, 0.62], 0.32[0.08, 0.56], and 0.33[0.21, 0.46], respectively). Seven trials compared NT-proBNP levels in patients with thyroid dysfunction before and after therapy, and significant drops in NT-proBNP levels were observed in patients with hyperthyroidism (SMD [95%CI] = -1.53[-2.50, -0.55]) upon achieving a euthyroid state. In contrast, increased NT-proBNP levels were observed in hypothyroid patients after treatment (SMD [95%CI] = 1.07[0.28, 1.85]).. Thyroid dysfunction can significantly affect NT-proBNP levels, which may change upon achieving a euthyroid state. Notably, the effect of thyroid dysfunction on cardiac function may depend on the underlying cardiac status. Thus, timely recognition and effective treatment of cardiac symptoms in patients with thyroid dysfunction are mandatory because the prognosis of HF may be improved with appropriate treatment of thyroid dysfunction.. https://www.crd.york.ac.uk/prospero, identifier CRD42022353700.

Topics: Heart Failure; Humans; Hyperthyroidism; Hypothyroidism; Natriuretic Peptide, Brain

Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Heart; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; COVID-19; Dyspnea; Heart Failure; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Natriuretic Peptides

Natriuretic peptides must be interpreted in their clinical context, especially in intensive care medicine. This overview presents the diagnostic, prognostic, and therapeutic significance of B‑type natriuretic peptide (BNP) and N‑terminal pro B‑type natriuretic peptide (NT-proBNP) in patients with cardiac dysfunction, kidney failure, sepsis, pulmonary embolism, acute respiratory distress syndrome (ARDS), acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and weaning from a respirator.. Natriuretische Peptide müssen gerade in der Intensivmedizin in ihrem klinischen Kontext interpretiert werden. In dieser Übersicht wird die diagnostische, prognostische und therapeutische Bedeutung von BNP und NT-proBNP bei Patienten mit kardialer Dysfunktion, Nierenversagen, Sepsis, Lungenembolie, ARDS, AECOPD und im Weaning vom Respirator dargestellt.

Topics: Biomarkers; Critical Care; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome

Heart failure (HF) is a dominant health problem with an overall poor prognosis. Natriuretic peptides (NPs) are upregulated in HF as a compensatory mechanism. They have been extensively used for diagnosis and risk stratification.. This review addresses the history and physiology of NPs in order to understand their current role in clinical practice. It further provides a detailed and updated narrative review on the utility of those biomarkers for risk stratification, monitoring, and guiding therapy in HF.. NPs show excellent predictive ability in heart failure patients, both in acute and chronic settings. Understanding their pathophysiology and their modifications in specific situations is key for an adequate interpretation in specific clinical scenarios in which their prognostic value may be weaker or less well evaluated. To better promote risk stratification in HF, NPs should be integrated with other predictive tools to develop multiparametric risk models. Both inequalities of access to NPs and evidence caveats and limitations will need to be addressed by future research in the coming years.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Risk Assessment

To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).. PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.. Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).. AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.

Topics: Animals; Heart Failure; Mice; Natriuretic Peptide, Brain; Rats; Stroke Volume; Ventricular Function, Left

Although the prevalence of heart failure has been increasing over time, the presentation of heart failure has been shifting, with a greater proportion of preserved ejection fraction and more slowly progressive symptoms that require recognition in the outpatient setting. These shifts have placed more of the diagnostic responsibility onto primary care physicians, who often are challenged to determine the etiology of common symptoms in patients who often have several other potential reasons for these symptoms. Establishing a diagnosis of heart failure requires a step-wise approach that includes physical exam (looking for multiple signs of hypervolemia), labs (B-type natriuretic peptide levels), and echocardiography (structural and functional measures). Diagnostic algorithms are particularly challenging in patients with obesity, which limits the assessment of intravascular volume on exam, the quality of cardiac imaging, and the diagnostic accuracy of B-type natriuretic peptide levels, which may be falsely low. In these challenging patients, the use of risk scores, invasive testing of intravascular volume, or empiric treatment of hypervolemia may be needed to determine whether symptoms are due to heart failure. Once a diagnosis of heart failure is established, several treatments can be beneficial, from diuretics to relieve congestion to various aspects of guideline-directed medical therapy, some of which vary according to the ejection fraction of the patient. In addition, a diagnosis of heart failure may alter the treatment plan for comorbidities, including selection of anti-hypertensive and glucose-lowering medications, and medical or surgical treatments for obesity. While a diagnosis of heart failure may be challenging in many patients with slowly progressive and non-specific symptoms, early recognition and treatment can be extremely effective at preventing hospitalizations, prolonging survival, and improving quality of life.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Quality of Life; Stroke Volume

This meta-analysis aims to evaluate the effects of levosimendan on B-type natriuretic peptide (BNP) levels in patients with decompensated heart failure and assess the efficacy and safety of levosimendan in treating left heart failure.. Randomized controlled trials (RCTs) were identified through searches in the Chinese Biomedical Literature Database (CBM), Chinese Academic Journal Full Text Database (CNKI), Wanfang Database (CECDB), VIP Chinese Scientific, PubMed, Cochrane Library, and Web of Science. Quality assessment and data extraction were performed for the included studies, and meta-analysis was conducted using Review Manager 5.2 software.. The meta-analysis revealed a statistically significant difference in the regulatory effect of levosimendan on BNP levels in patients with stage III heart failure compared to the control group [OR = 2.12, 95% CI (1.22, 3.67), P = .008, I2 = 37%, Z = 2.67]. Additionally, leosimendan showed a significant effect on BNP levels in patients with stage IV heart failure [OR = 1.88, 95% CI (1.27, 2.79), P = .002, I2 = 0%, Z = 3.14], compensatory heart failure [OR=2.97, 95% CI (1.81, 4.86), P < .0001, I2 = 55%, Z = 4.32], and decompensated heart failure [OR = 1.98, 95% CI (1.59, 2.47), P < .00001, I2 = 76%, Z = 6.07].. Levosimendan administration demonstrated improved cardiac function and a significant reduction in plasma BNP levels in patients with decompensated heart failure.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Patients; Simendan

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

Heart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking.. The genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered. In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in. URL: https://www.. gov; Unique identifier: NCT00475852.

Topics: Genome-Wide Association Study; Guanine Nucleotide Exchange Factors; Heart Failure; Humans; Natriuretic Peptide, Brain; Patient Readmission; Vascular Endothelial Growth Factor A

N terminal pro brain natriuretic peptide (NT-proBNP) plays an important role in the diagnosis and prognosis of heart failure (HF). The plasma level of NT-proBNP in atrial fibrillation (AF) patients was higher than of sinus rhythm patients. In HF, NT-proBNP levels are affected by the concomitant presence of AF, making it difficult to distinguish between HF and AF in patients with elevated NT-proBNP. Several other diseases, such as renal failure and pulmonary embolism, are known to further increase NT-proBNP levels in patients with concomitant HF. Therefore, NT-proBNP is a sensitive but non-specific marker for the detection of HF. AF is very important in this regard because among patients with HF regardless of ejection fraction, symptoms such as shortness of breath and atrial enlargement develop and can mimic HF. In the present study, we investigated whether the prognostic value of natriuretic peptides in HF holds true for patients with concomitant AF.

Topics: Atrial Fibrillation; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Background Natriuretic peptides have been recommended as biomarkers for the diagnosis and prognosis of patients with heart failure and are often elevated in the setting of acute kidney injury. We sought to demonstrate the associations between increased baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) and adverse renal outcomes in patients with moderate-to-severe acute kidney injury. Methods and Results We reviewed electronic medical records of consecutive patients with acute kidney injury stage 2 and 3 admitted to the Cleveland Clinic between September 2011 and December 2021. Patients with NT-proBNP levels collected before renal consultation or dialysis initiation were included. Adverse renal outcomes included dialysis requirement and dialysis dependence defined as patients undergoing dialysis within 72 hours before hospital discharge or in-hospital mortality. In our study cohort (n=3811), 2521 (66%) patients underwent dialysis, 1619 (42%) patients became dialysis dependent, and 1325 (35%) patients had in-hospital mortality. After adjusting for cardiorenal risk factors, compared with the lowest quartile, the highest quartile of NT-proBNP (≥18 215 pg/mL) was associated with increased likelihood of dialysis requirement (adjusted odds ratio [OR], 2.36 [95% CI, 1.87-2.99]), dialysis dependence (adjusted OR, 1.89 [95% CI, 2.53-1.34]), and in-hospital mortality (adjusted OR, 1.34 [95% CI, 1.01-1.34]). Conclusions Increased NT-proBNP was associated with an increased risk of dialysis requirement, becoming dialysis dependent, and in-hospital mortality in patients with moderate-to-severe acute kidney injury.

Topics: Acute Kidney Injury; Biomarkers; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Vasodilator Agents

Heart failure is one of the leading healthcare problems in the world. Clinical data lacks sensitivity and specificity in the diagnosis of heart failure. Laboratory biomarkers are a non-invasive method of assessing suspected decompensated heart failure. Biomarkers such as natriuretic peptides have shown promising results in the management of heart failure. The literature does not provide comprehensive guidance in the utilization of biomarkers in the setting of acute heart failure syndrome. Many conditions that manifest with similar pathophysiology as acute heart failure syndrome may demonstrate positive biomarkers. The following is a review of biomarkers in heart failure, enlightening their role in diagnosis, prognosis and management of heart failure.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis; Syndrome

There is disparity between the sexes in cardiovascular diseases including heart failure (HF). This study aimed to investigate the effect of periodontal disease (PD) on plasma B-type natriuretic peptide (BNP) concentration across sex, age, and menopausal status, as well as the interaction effect of PD and diabetes mellitus (DM) on BNP. This large-scale prospective cohort study enrolled 7539 individuals with no myocardial infarctions or angina pectoris at baseline from the general Japanese population. The association between baseline number of missing teeth (MT) and the longitudinal changes in BNP over 5 years (ΔBNP) was evaluated according to sex and menopausal status. Among 7539 participants, 3190 were postmenopausal women with a mean age ± standard deviation of 61.1 ± 7.6 at baseline. Multivariate analysis revealed a positive association between MT and ΔBNP among postmenopausal women even after adjusting for covariates, including traditional HF risk factors (coefficient, 0.210; 95% confidence interval [CI], 0.107 to 0.312; P < 0.001), but not in men aged > 50. Including an interaction term (MT × DM) in the multivariate model revealed a positive interaction between MT and DM in ΔBNP among postmenopausal women (coefficient for interaction, 1.365; 95% CI, 0.902 to 1.827; P for interaction < 0.001). In conclusion, our study showed a positive association between MT and ΔBNP, as well as a positive effect of the interactive association between MT and DM, among postmenopausal women. Our results suggest a sex difference of an adverse effect of PD on initial myocardial wall stress in the ventricles.

Topics: Diabetes Mellitus; Female; Heart Failure; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Postmenopause; Prospective Studies; Tooth Loss

Emerging evidence suggests that epicardial fat thickness (EFT) may be a critical feature to understand cardiac health and determine the risk of heart failure. The current review critically assesses and discusses evidence on the efficiency of measuring EFT, in comparison to the well-known markers B-type natriuretic peptide (BNP) and its N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP), as a prognostic and diagnostic approach in individuals with or at risk of heart failure. A systematic approach was undertaken to search major databases, PubMed, Scopus, Google Scholar and the Cochrane library to identify studies that quantified EFT and serum BNP/NT-proBNP levels in individuals with or at risk of heart failure. Twelve studies met the inclusion criteria and a total of 1983 participants were included in this systematic review. Evidence shows a clear association between increased EFT and elevated BNP/NT-proBNP levels in individuals with metabolic disease and suggests that both methods can be used for heart failure diagnosis and prognosis. However, due to the broad spectrum of challenges linked with measuring EFT, BNP/Pro-BNP is the predominant method used for heart failure diagnosis and prognosis in clinical practice. Nonetheless, measuring EFT provides a powerful and reproducible diagnostic tool for risk stratification and heart failure diagnosis and prognosis. Importantly, measuring EFT proves valuable to validate BNP/NT-proBNP levels to predict heart failure, especially due to its non-invasive nature.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Natriuretic peptides (NP) play a key role in the regulation of the body's water and salt balance and may effectively contribute to the diagnosis of patients with heart failure. NP-measurements are increasingly used internationally, but despite being available for more than ten years, neither a rational implementation nor clinical guidelines for use exist in Denmark. In this review, we present a practical approach to the use of NP in general practice and in the emergency department based on a newly published position paper from the Danish Society of Cardiology.

Topics: Biomarkers; Cardiology; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides

This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information.. Through inhibition of neprilysin, Sac/Val may increase BNP concentrations.. In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12.. Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [-30% to +41%]; P = 0.36) or week 12 (+1% [-36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by -30% (-50% to -8%) and -32% (-54% to -1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34% to +115%]), unchanged (+34% [-15% to +205%]), or increased (+57% [-12% to +14%]).. In this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Diuretics; Drug Combinations; Enalapril; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Tetrazoles; Valsartan; Vasodilator Agents

CME: Heart Failure- Overview, Clinical Manifestation, Diagnosis and Management

Topics: Biomarkers; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Switzerland

To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics.. Individual patient level data meta-analysis and modelling study.. Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies.. Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated.. Adjudicated diagnosis of acute heart failure.. Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure.. In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach.. PROSPERO CRD42019159407.

Topics: Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Observational Studies as Topic; Peptide Fragments; Predictive Value of Tests; Prospective Studies

Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho-vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline-recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFrEF.. An individual patient data (IPD) meta-analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline-directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6-month changes in 6-min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT-proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of -13 points (95% CI -17, -10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT-proBNP <1600 pg/ml, regardless of the cardiac resynchronization therapy indication status.. An IPD meta-analysis suggests that BAT improves exercise capacity, NYHA class, and QoL in HFrEF patients receiving GDMT. These clinically meaningful improvements were consistent across the range of patients studies. BAT was also associated with an improvement in NT-proBNP in subjects with a lower baseline NT-proBNP.

Topics: Baroreflex; Electric Stimulation Therapy; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Randomized Controlled Trials as Topic; Stroke Volume

Early detection and risk stratification of patients with heart failure (HF) are crucial to improve outcomes. Given the complexity of the pathophysiological processes of HF and the involvement of multi-organ systems in different stages of HF, clinical prognostication of HF can be challenging. In this regard, several biomarkers have been investigated for diagnosis, screening, and risk stratification of HF patients. These biomarkers can be classified as biomarkers of myocardial stretch such as B-type natriuretic peptide, biomarkers of neurohormonal activation, biomarkers of inflammation and oxidative stress and biomarkers of cardiac hypertrophy, fibrosis and remodeling. In this paper, we summarize current evidence supporting the use of selected biomarkers in HF. We review their diagnostic, prognostic and therapeutic role in the management of HF. We also discuss potential factors limiting the use of these novel biomarkers in the clinical practice and highlight the challenges of adopting a multi-biomarker strategy.

Topics: Biomarkers; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prognosis

Natriuretic peptides have been at the forefront of biomarker use in heart disease and have been universally recommended as the ideal biomarker in the setting of heart failure. Soluble ST2 is one such biomarker which has found value as a prognostic marker and can be used individually or along with natriuretic peptides in order to prognosticate patients with heart failure. Leading cardiovascular organisations have recognised this biomarker, though its role as a diagnostic marker is yet to be determined. We aim to investigate the role of sST2 in heart failure in the existing literature.

Topics: Biomarkers; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis

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

Physical training has been reported to attenuate myocardial stress and inflammation in heart failure (HF). We aimed to assess the impact of physical training on B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as biomarkers of inflammation-C-reactive protein, tumor necrosis factor α (TNF-α), and interleukins (ILs). A systematic electronic literature search was conducted up to May 2021 in PubMed, Cochrane Library, CINAHL, Embase, and SPORTDiscus to identify randomized clinical trials reporting associations between any formal physical training intervention and biomarker levels in patients with HF. Random-effects meta-analyses was used to calculate pooled correlations between physical training and blood biomarkers. Biomarker outcomes were expressed as mean difference or ratio of means and 95% confidence interval between the intervention and control groups, according to the normality of the data. A total of 38 trials were included in the final meta-analysis (2,652 randomized patients). Physical training was associated with decreased B-type natriuretic peptide (p = 0.02), NT-proBNP (p <0.01), C-reactive protein (p <0.00001), TNF-α (p = 0.03), IL-6 (p = 0.04), and IL-1β (p = 0.001). Aerobic continuous training was associated with a 35% reduction in NT-proBNP (p = 0.01); ≥150 min/week of exercise was associated with a greater reduction in TNF-α levels (p = 0.0004), and aerobic interval training was associated with lower IL-6 levels (p = 0.01). In conclusion, physical training in patients with HF is associated with beneficial effects on natriuretic peptides and biomarkers of inflammation because they were all reduced by the intervention.

Topics: Biomarkers; C-Reactive Protein; Heart Failure; Humans; Inflammation; Interleukin-6; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Tumor Necrosis Factor-alpha

Angiotensin receptor neprilysin inhibitors (ARNI), sodium-glucose cotransporter 2 inhibitors (SGLT2i), soluble guanylate cyclase stimulators (sGCs), and the traditional golden triangle standard-of-care (SOC) are effective drugs for heart failure. We aimed to assess the efficacy of 4 interventions in these patients.. PubMed, The Cochrane Library, Embase, and Web of Science databases were electronically searched to collect randomized controlled trials of 3 novel drugs in the treatment of heart failure from inception to September 1st, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk bias of included studies. Stata 16.0 software was used for network meta-analysis.. A total of 17 randomized controlled trial involving 38,088 patients were included. The results of network meta-analysis: in terms of heart failure rehospitalization rate, 3 novel drugs lower than SOC [ARNI (OR = 0.77, 95% CI: 0.71-0.83), SGLT2i (OR = 0.70, 95% CI: 0.63-0.77), sGCs (OR = 0.88, 95% CI: 0.78-0.99)], and SGLT2i was also lower than sGCs (OR = 0.79, 95% CI: 0.68-0.93). In terms of all-cause mortality, ARNI was lower than SOC (OR = 0.81, 95% CI: 0.66-0.99). In terms of cardiovascular mortality, ARNI and SGLT2i was lower than SOC (ARNI [OR = 0.80, 95% CI: 0.70-0.92], SGLT2i [OR = 0.87, 95% CI: 0.76-0.99]). In terms of rates of cardiovascular death or heart failure rehospitalization, 3 novel drugs lower than SOC (ARNI [OR = 0.76, 95% CI: 0.71-0.82], SGLT2i [OR = 0.76, 95% CI: 0.70-0.82], sGCs [OR = 0.87, 95% CI: 0.78-0.97]). In terms of Kansas city cardiomyopathy questionnaire score, ARNI and SGLT2i was superior to SOC (ARNI [MD = 1.43, 95% CI: 0.43-2.42], SGLT2i [MD = 1.88, 95% CI: 1.12-2.65]). In terms of N-terminal pro-B-type natriuretic peptide outcome indexes, SGLT2i was superior to SOC (MD = -134.63, 95% CI: -237.70 to -31.56). The results of Surface under the cumulative ranking sequencing: in terms of heart failure rehospitalization rate and rates of cardiovascular death or heart failure rehospitalization, the ranking was SGLT2i>ARNI>sGCs>SOC. in terms of all-cause mortality and cardiovascular mortality, the ranking was ARN>SGLT2i>sGCs>SOC. in terms of Kansas city cardiomyopathy questionnaire score and N-terminal pro-B-type natriuretic peptide outcome indexes, the ranking was SGLT2i>ARN>SOC.. The available evidence suggests that all 3 novel heart failure drugs can improve the prognosis of heart failure. ARNI may be the most effective in reducing mortality, SGLT2i may be the most effective in improving quality of life, while sGCs may be inferior to ARNI and SGLT2i.

Topics: Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Stroke Volume

Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4].. Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume

Heart failure leading to cardiac ascites is an extremely rare and underrecognized entity in clinical practice. Recognizing cardiac ascites can be difficult, especially since patients presenting with ascites may have more than 1 etiology. Various biomarkers are available to aid in the diagnosis of cardiac ascites, though with differing sensitivities and specificities. Such biomarkers include serum albumin, ascitic albumin and protein, as well as serum N-terminal pro-brain natriuretic peptide (NT-proBNP). While serum NT-proBNP is a powerful biomarker in distinguishing the etiology of ascites and monitoring treatment progression, its cost can be prohibitive in low-resource settings. Clinicians practicing under these circumstances may opt to rely on other parameters to manage their patients. We go on further to report a series of 3 patients with cardiac ascites to illustrate how these biomarkers may be employed in the management of this patient population. Clinicians should always keep in mind the differential diagnosis of cardiac failure as a cause of ascites. The resolution of cardiac ascites may serve as a surrogate clinical marker for response to antifailure therapy in lieu of NT-proBNP at resource-scarce centers.

Topics: Ascites; Biomarkers; Diagnosis, Differential; Heart; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Systematic evaluation of the efficacy of natriuretic recombination in human brain on disease myocardial infarction, left ventricular heart failure, and the efficacy and safety of long-term left ventricular remodeling.. Computerized search of CNKI, Wanfang database, Wipro Chinese Technology Publications (VIP) numerical database, Chinese Biomedical Literature Database (CBM), Medline Cochrane Library, clinical Trail.Gov clinical collection, and other documents. Randomized controlled trials (RCT) of recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction from inception to December 2021 were searched. Based on the Jadad scale, inclusion-exclusion data for diseases were collected and elaborated by meta by RevMan 5.3 simulation software. In a total of 23 randomized controlled trials, 2 024 cases were used as the basic data, the control group was routinely treated for 1 012 cases, and 1 012 cases in the experimental group were also treated with natriuretic peptide in the recombinant human brain on the previous basis.. In terms of overall efficacy, the experimental group was better than the control group, statistically significant (OR = 4.30, 95% CI (3.26, 5.67),. In patients with acute myocardial infarction and left ventricular remodeling, if treated with a heavy treatment of the group of cerebral natriuretic peptide mode, it can increase clinical treatment, improve the cardiac effect, inhibit ventricular remodeling, improve blood pressure and heart rhythm, and have greater clinical treatment and safety.

Topics: Brain; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Function, Left; Ventricular Remodeling

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

Chronic heart failure (CHF) can be classified as heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF). Currently, there is an unmet need for a minimally invasive diagnostic tool for different forms of CHF. We aimed to investigate the diagnostic potential of circulating microRNAs (miRNAs) for the detection of different CHF forms via a systematic review and meta-analysis approach.. Comprehensive search on Medline, Web of Science, Scopus, and EMBASE identified 45 relevant studies which were used for qualitative assessment. Out of these, 29 studies were used for qualitative and quantitative assessment and allowed to identify a miRNA panel able to detect HFrEF and HFpEF with areas under the curve (AUC) of 0.86 and 0.79, respectively. A panel of eight miRNAs (hsa-miR-18b-3p, hsa-miR-21-5p, hsa-miR-22-3p, hsa-miR-92b-3p, hsa-miR-129-5p, hsa-miR-320a-5p, hsa-miR-423-5p, and hsa-miR-675-5p) detected HFrEF cases with a sensitivity of 0.85, specificity of 0.88 and AUC of 0.91. A panel of seven miRNAs (hsa-miR-19b-3p, hsa-miR-30c-5p, hsa-miR-206, hsa-miR-221-3p, hsa-miR-328-5p, hsa-miR-375-3p, and hsa-miR-424-5p) identified HFpEF cases with a sensitivity of 0.82 and a specificity of 0.61.. Although conventional biomarkers (N-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide) presented a better performance in detecting CHF patients, the results presented here pointed towards specific miRNA panels with potential additive values to circulating natriuretic peptides in the diagnosis of different classes of CHF. Equally important, miRNAs alone showed a reasonable capacity for 'ruling out' patients with HFrEF or HFpEF. Additional studies with large populations are required to confirm the diagnostic potential of miRNAs for sub-classes of CHF.

Topics: Biomarkers; Heart Failure; Humans; MicroRNAs; Natriuretic Peptide, Brain; Stroke Volume

Oral iron supplement is commonly prescribed to heart failure patients with iron deficiency. However, the effects of oral iron for heart failure remain controversial. This study included randomized controlled trials (RCTs) for meta-analysis to evaluate the effects of oral iron for heart failure patients.. Nine databases (The Cochrane Library, Embase, PubMed, CINAHL, Web of science, CNKI, SinoMed, VIP, and Wanfang) were searched for RCTs of oral iron for heart failure from inception to October 2021. The effects were assessed with a meta-analysis using Revman 5.3 software. The trial sequential analysis was performed by TSA 0.9.5.10 beta software. The risk of bias of trials was evaluated via Risk of Bias tool. The evidence quality was assessed through GRADE tool.. Four studies including 582 patients with heart failure and iron deficiency were enrolled. The results indicated that oral iron treatment could improve left ventricular ejection fraction (LVEF, MD = 1.52%, 95% CI: 0.69 to 2.36,. This analysis showed that oral iron could improve cardiac function measured by LVEF, and iron stores measured serum ferritin, but lack of effect on exercise capacity measured by 6 MWT, and iron stores measured by hemoglobin. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.

Topics: Heart Failure; Humans; Iron; Iron Deficiencies; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Stroke Volume

Heart failure (HF) is a high prevalent syndrome with significant burden worldwide. B-type natriuretic peptide (BNP) and N-terminal proBNP are the gold standard biomarkers in HF management. Although useful in clinical practice, they have limitations as their expression can be influenced by ventricular function, aging, obesity, renal failure and atrial arrhythmias. MicroRNAs have recently emerged as potential diagnostic and prognostic biomarkers, given that they are related to cell growth, proliferation, differentiation, and metabolism. An increasing amount of research has highlighted some microRNAs for their potential as HF biomarkers. However, different study designs, methods and study groups have led to inconsistent results.. We performed a systematic search of available literature on Pubmed and Scopus reporting the prognostic value of microRNAs in HF, followed by a review of risk of bias, according to Quadas Group Standards. Simultaneously, microRNAs' potential as differential diagnosis and severity biomarkers was also analyzed. Studies have described circulating microRNA as potential diagnostic, prognostic, and severity markers. Mir-622, -519 and -499 were significantly related to HF with reduced ejection fraction, whereas miR-22-3p revealed greater ability as a severity biomarker. Let-7i-5p, miR-223-5p, miR-423-5p, miR-21, miR-1306-5p and miR-122 serum expressions presented a consistent correlation with HF prognosis. Furthermore, identified miR targets were associated with signaling pathways already known to be involved in HF progression.. Several miRs were related to HF pathophysiology and demonstrated potential as biomarkers for disease progression. MicroRNAs have a promising role in HF, and although unquestionable, we require a deeper and broader understanding of their role and function for future research.

Topics: Biomarkers; Circulating MicroRNA; Heart Failure; Humans; MicroRNAs; Natriuretic Peptide, Brain; Prognosis

Heart failure (HF) is the only cardiovascular disease with an ever increasing incidence. HF, through reduced functional capacity, frequent exacerbations of disease, and repeated hospitalizations, results in poorer quality of life, decreased work productivity, and significantly increased costs of the public health system. The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. At this moment, there is a lack of universal parameters or scales on the basis of which we could easily capture the moment of deterioration of HF patients' condition. Hence, it is crucial to identify such factors which at the same time will be widely available, cheap, and easy to use. We can find many studies showing different predictors of unfavorable outcome in HF patients: thorough assessment with echocardiography imaging, exercise testing (e.g., 6-min walk test, cardiopulmonary exercise testing), and biomarkers (e.g., N-terminal pro-brain type natriuretic peptide, high-sensitivity troponin T, galectin-3, high-sensitivity C-reactive protein). Some of them are very promising, but more research is needed to create a specific panel on the basis of which we will be able to assess HF patients. At this moment despite identification of many markers of adverse outcomes, clinical decision-making in HF is still predominantly based on a few basic parameters, such as the presence of HF symptoms (NYHA class), left ventricular ejection fraction, and QRS complex duration and morphology.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Stroke Volume; Ventricular Function, Left

Heart failure (HF) is a significant cause of morbidity and mortality worldwide. Circulating biomarkers reflecting pathophysiological pathways involved in HF development and progression may assist clinicians in early diagnosis and management of HF patients. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload. The roles of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification in HF have been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the role of NPs as a guide to HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, with independent value to NPs. Other biomarkers evaluated as predictors of adverse outcome are galectin-3, growth differentiation factor 15, mid-regional pro-adrenomedullin, and makers of renal dysfunction. Multi-marker scores and genomic, transcriptomic, proteomic, and metabolomic analyses could further refine HF management.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis; Proteomics

Several heart failure (HF) web-based risk scores are currently used in clinical practice. Currently, we lack head-to-head comparison of the accuracy of risk scores. This study aimed to assess correlation and mortality prediction performance of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, which includes clinical variables + medications; Seattle Heart Failure Model (SHFM), which includes clinical variables + treatments + analytes; PARADIGM Risk of Events and Death in the Contemporary Treatment of Heart Failure (PREDICT-HF) and Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, which also include biomarkers, like N-terminal pro B-type natriuretic peptide (NT-proBNP).. A total of 1166 consecutive patients with HF from different aetiologies that had NT-proBNP measurement at first visit were included. Discrimination for all-cause mortality was compared by Harrell's C-statistic from 1 to 5 years, when possible. Calibration was assessed by calibration plots and Hosmer-Lemeshow test and global performance by Nagelkerke's R. None of the contemporary risk scores examined showed a clear superiority over the rest. BCN-Bio-HF calculator provided the best discrimination and overall performance with overestimation of risk. MAGGIC-HF showed the best calibration, and SHFM and PREDICT-HF tended to underestimate risk. Regular updating and recalibration of online web calculators seems necessary to improve their accuracy as HF management evolves at unprecedented pace.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.

Topics: Biomarkers; COVID-19; Diabetes Mellitus, Type 2; Disease Management; Glycated Hemoglobin; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

A number of circulating biomarkers are currently utilized for the diagnosis of chronic heart failure with preserved ejection fraction (HFpEF). However, due to HFpEF heterogeneity, the accuracy of these biomarkers remains unclear.. This study aimed to systematically determine the diagnostic accuracy of currently available biomarkers for chronic HFpEF.. PubMed, Web of Science, MEDLINE and SCOPUS databases were searched systematically to identify studies assessing the diagnostic accuracy of biomarkers of chronic HFpEF with left ventricular ejection fraction (LVEF) ≥50%. All included studies were independently assessed for quality and relevant information was extracted. Random-effects models were used to estimate the pooled diagnostic accuracy of HFpEF biomarkers.. The search identified 6145 studies, of which 19 were included. Four biomarkers were available for meta-analysis. The pooled sensitivity of B-type natriuretic peptide (BNP) (0.787, 95% confidence interval [CI] 0.719-0.842) was higher than that of N-terminal pro-BNP (NT-proBNP) (0.696, 95% CI 0.599-0.779) in chronic HFpEF diagnosis. However, NT-proBNP showed improved specificity (0.882, 95% CI 0.778-0.941) compared to BNP (\\0.796, 95% CI 0.672-0.882). Galectin-3 (Gal-3) exhibited a reliable diagnostic adequacy for HFpEF (sensitivity 0.760, 95% CI 0.631-0.855; specificity 0.803, 95% CI 0.667-0.893). However, suppression of tumorigenesis-2 (ST2) displayed limited diagnostic performance for chronic HFpEF diagnosis (sensitivity 0.636, 95% CI 0.465-0.779; specificity 0.595, 95% CI 0.427-0.743).. NT-proBNP and BNP appear to be the most reliable biomarkers in chronic HFpEF with NT-proBNP showing higher specificity and BNP showing higher sensitivity. Although Gal-3 appears more reliable than ST2 in HFpEF diagnosis, the conclusions are limited as only three studies were included in this meta-analysis.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Ventricular Function, Left

The high burden of heart failure in nursing-home populations is due to advanced age and comorbidities. Heart failure is often undiagnosed or misdiagnosed in this population and therefore remains untreated. We review the use of natriuretic peptide biomarkers for screening heart failure in nursing-home residents. The study was performed in accordance with recommendations from the Cochrane Collaboration using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and is registered in PROSPERO Register of Systematic Reviews. Databases PubMed, Embase, and Trip were searched from 2000 to March 2019, supplemented by hand-searching of references. Studies investigating the nursing-home population were included. The prevalence of heart failure among nursing-home residents was higher than in the general population of comparable age (23% vs 10%, respectively). The rate of misdiagnosis in nursing homes ranged from 25 to 76%. NT-proBNP was the most commonly used natriuretic peptide biomarker for heart failure screening. The mean value of NT-proBNP was significantly higher in residents with heart failure than in residents overall (pooled means of 2409 pg/mL vs 1074 pg/mL, respectively). In comparison with current guidelines, the proposed cut-off values for ruling out heart failure were higher in the analyzed studies, with ranges of 230-760 pg/mL for NT-proBNP and 50-115 pg/mL for BNP. NT-proBNP and BNP are used for screening heart failure in the nursing-home population. The current screening cut-off values are probably too low for use in nursing homes. Our most conservative estimation for ruling out heart failure is an NT-proBNP cut-off value of 230 pg/mL.

Topics: Biomarkers; Comorbidity; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Nursing Homes; Peptide Fragments

N-terminal pro-brain natriuretic peptide (NT-pro BNP) increases in patients with heart failure and renal failure. Hemodialysis is a useful treatment to these patients. The aim of this study was to conduct a systematic and meta-analysis to evaluate the influence of hemodialysis on NT-pro BNP concentration.. Relevant studies were identified by searching in PubMed, Medline, Embase, OVID, Web of Science, China Biology Medicine (CBM) and Google Scholar. Standard errors of mean difference along with its 95% CI were calculated to assess the association of hemodialysis and NT-pro BNP concentration. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored.. Individual patient data was obtained from 270 participants in seven articles suffered from chronic renal failure with regular hemodialysis, which was standard normal distribution. A fixed effects model suggested a pooled mean difference of 79.265 (95% CI: -331.172-489.702) without heterogeneity (Q = 0.70 df = 6 p = 0.994 I. Finding of this systematic review and meta-analysis demonstrated that NT-pro BNP may not been influenced by hemodialysis, and it could not been used to determine if heart failure is improving in patients with renal failure who are treated with hemodialysis.

Topics: Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis

Levosimendan, a calcium (Ca. We searched PubMed, Embase, and CENTRAL from 1994 to August 2019 to compare the efficacy of levosimendan infusion for the treatment of advanced heart failure with that of other agents (placebo, dobutamine, furosemide, and prostaglandin E1). Levels of B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP), and left ventricular ejection fraction (LVEF) and heart rate (HR) were analyzed. The count data were analyzed by the standardized mean difference (SMD) and its 95% confidence interval (CI) to determine the effect size. We chose the random effect model or the fixed effect model according to the heterogeneity.. Nine randomized controlled trials with 413 patients were ultimately enrolled. Compared with other agents (placebo, dobutamine, furosemide, and prostaglandin E1), levosimendan significantly reduced the BNP level (SMD - 0.91; 95% CI - 1.44 to - 0.39; p = 0.001; I. Our meta-analysis suggests that intravenous levosimendan can reduce BNP level and increase LVEF in patients with advanced heart failure to reduce the mortality at the shortest follow-up available.

Topics: Cardiotonic Agents; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Simendan; Stroke Volume; Ventricular Function, Left

Discuss the literature and describe strategies to overcome barriers of inpatient initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).. A PubMed, EMBASE, and Google Scholar literature search (January 2014 to June 2020) limited to English language articles was conducted with the following terms:. Included articles described inpatient initiation of sacubitril/valsartan or described its impact on BNP, NT-proBNP, diuretic dosing, or cost of care.. A total of 20 studies were identified based on included search terms.. Sacubitril/valsartan should be considered for hemodynamically stable patients with HFrEF (New York Heart Association class II or III), potassium <5.2 mmol/L, without a history of angioedema, and after a 36-hour washout from angiotensin-converting enzyme (ACE) inhibitor or aliskiren, if applicable. An appropriate dose can be determined based on the patient's previous ACE inhibitor or angiotensin receptor blocker dose and/or blood pressure along with patient-specific factors. To overcome barriers of use, the following are recommended: NT-proBNP or BNP with establishment of a new baseline 1 month after initiation may be used for prognosis or diagnosis; careful monitoring of diuretic requirements; utilization of multiple strategies to overcome cost barriers; and use of interdisciplinary care.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Pressure; Clinical Trials as Topic; Drug Combinations; Heart Failure; Hospitalization; Humans; Inpatients; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Valsartan

Treatment of patients with heart failure with reduced ejection fraction (HFrEF) with currently available therapies reduces morbidity and mortality. However, implementation of these therapies is a problem with only few patients achieving guideline-recommended maximal doses of therapy. In an effort to improve guideline adherence and uptitration, several trials have investigated a biomarker-guided strategy (using natriuretic peptide targets in specific), but although conceptually promising, these trials failed to show a consistent beneficial effect on outcomes. In this review, we discuss different methodological issues that may explain the failure of these trials and offer potential solutions. Moreover, alternative approaches to increase heart failure guideline adherence are evaluated.

Topics: Guideline Adherence; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Stroke Volume; Ventricular Dysfunction, Left

Acute decompensated heart failure (ADHF), with an incidence of 1-2%, is a clinical syndrome with significant morbidity and mortality despite therapeutic advancements and ongoing clinical trials. A recent therapeutic approach to patients with ADHF includes combination therapy with hypertonic saline solution (HSS) and furosemide, based on the hypothesis that resistance to loop diuretics occurs because of achievement of plateau in water and sodium excretion in patients receiving long-term loop diuretic therapy.. Our aim was to conduct a meta-analysis to evaluate the efficiency of combination HSS plus furosemide therapy in patients with ADHF in terms of mortality, readmissions, length of hospital stay, kidney function, urine output, body weight, and B-type natriuretic peptide (BNP).. A total of 14 studies-four observational and ten randomized studies (total 3398 patients)-were included in the meta-analysis.. Our results demonstrate the superiority of combination HSS plus furosemide therapy over furosemide alone in terms of kidney function preservation (mean creatinine difference - 0.33 mg/dL; P < 0.00001), improved diuresis (mean difference [MD] 581.94 mL/24 h; P < 0.00001) and natriuresis (MD 57.19; P < 0.00001), weight loss (MD 0.99 kg; P < 0.00001), duration of hospital stay (MD - 2.72 days; P < 0.00001), readmissions (relative risk 0.63; P = 0.01), and mortality (relative risk 0.55; P < 0.00001). However, no difference in BNP levels was detected (MD 19.88 pg/mL; P = 0.50).. Despite the heterogeneity and possible risk of bias among the studies, results appear promising on multiple aspects. A clear need exists for future randomized controlled trials investigating the role of combination HSS plus furosemide therapy to clarify these effects and their possible mechanisms.

Topics: Body Weight; Diuresis; Diuretics; Drug Therapy, Combination; Furosemide; Heart Failure; Humans; Kidney Function Tests; Length of Stay; Natriuretic Peptide, Brain; Observational Studies as Topic; Patient Readmission; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic; Weight Loss

Several large trials have demonstrated cardiac benefits in patients with and without established cardiovascular disease treated with sodium-glucose co-transporter 2 inhibitors (SGLT2i). Most recently, in patients with heart failure with reduced ejection fraction (HFrEF), the risk of worsening HF or cardiovascular death was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. Biomarkers may provide insight into understanding the mechanism of cardiovascular benefit observed in patients receiving SLGT2i. Several mechanisms have been proposed, including improvement in ventricular unloading due to the natriuretic effects, afterload reduction via reduction in blood pressure and improvement in vascular function, improvement in cardiac metabolism and bioenergetics, and reduction in cardiac fibrosis and necrosis, among others.. We discuss several animal and human studies on the effect of SGLT2i on various biomarkers. Modest reduction or blunting of rise over time in concentrations of atrial natriuretic peptide, B-type natriuretic peptide, and N-terminal pro B-type natriuretic peptide and reduction in high-sensitivity troponin has been observed in patients receiving SLGT2i. Concentrations of biomarkers such as sST2 and galectin-3 have been unchanged whereas inflammatory markers such as fibronectin 1, interleukin-6, matrix metalloproteinase 7, and tumor necrosis factor-1 are decreased with SGLT2i therapy.. The effect of SLGT2i on various circulating biomarkers allows insight into the understanding of mechanisms of cardiovascular benefits with SGLT2i use. Further studies are needed to understand such mechanisms and to understand how biomarkers can be used for risk prediction and personalization of care in patients receiving SLGT2i.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Troponin

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cause of Death; Drug Combinations; Heart Failure; Hospitalization; Humans; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making. We first summarize the recent development of key HF risk prediction tools that can be applied broadly at a population level to estimate risk of incident HF. Next, we provide an in-depth description of the clinical utility of biomarkers to personalize risk estimation in select patients at the highest risk of developing HF. We also discuss integration of genomics-enhanced approaches (eg,

Topics: Antineoplastic Agents; Autoimmune Diseases; Biomarkers; Cardiac Imaging Techniques; Cardiotoxicity; Carrier Proteins; Comorbidity; Connectin; Female; Genomics; Heart Failure; HIV Infections; Humans; Liver Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Prealbumin; Precision Medicine; Pregnancy; Premature Birth; Radiotherapy; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Troponin T

Hypoalbuminemia (HA) is common in HF, however, its pathophysiology and clinical implications are poorly understood. While multiple studies have been published in the past decade investigating the role of serum albumin in HF, there is still no consensus on the prognostic value of this widely available measure. The objective of this study is to assess the prognostic role of albumin in heart failure (HF) patient.. Unrestricted searches of MEDLINE, EMBASE, Cochrane databases were performed. The results were screened for relevance and eligibility criteria. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The Begg and Mazumdar rank correlation test was utilized to evaluate for publication bias.. A total of 48 studies examining 44,048 patients with HF were analyzed. HA was found in 32% (95% confidence interval [CI] 28.4%-37.4%) HF patients with marked heterogeneity (I2 = 98%). In 10 studies evaluating acute HF, in-hospital mortality was almost 4 times more likely in HA with an odds ratios (OR) of 3.77 (95% CI 1.96-7.23). HA was also associated with a significant increase in long-term mortality (OR: 1.5; 95% CI: 1.36-1.64) especially at 1-year post-discharge (OR: 2.44; 95% CI: 2.05-2.91; I2 = 11%). Pooled area under the curve (AUC 0.73; 95% CI 0.67-0.78) was comparable to serum brain natriuretic peptide (BNP) in predicting mortality in HF patients.. Our results suggest that HA is associated with significantly higher in-hospital mortality as well as long-term mortality with a predictive accuracy comparable to that reported for serum BNP. These findings suggest that serum albumin may be useful in determining high-risk patients.

Topics: Heart Failure; Hospital Mortality; Humans; Hypoalbuminemia; Length of Stay; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Risk Factors; Serum Albumin

Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.

Topics: Acute Disease; Body Fluids; Cardio-Renal Syndrome; Cardiotoxins; Comorbidity; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Myocardial Contraction; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Renin-Angiotensin System; Symptom Assessment; Vascular Resistance; Vasoconstriction; Vasodilator Agents

Heart failure is a complex clinical syndrome that usually presents with breathlessness, leg edema, and fatigue. Clinically measurable natriuretic neurohormones such as B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are elevated in people with heart failure. We conducted a health technology assessment of BNP and NT-proBNP tests for people with suspected heart failure, which included an evaluation of diagnostic accuracy, clinical impact, cost-effectiveness, the budget impact of publicly funding BNP and NT-proBNP tests, and patient preferences and values.. We performed a literature search of previously published systematic reviews of the clinical evidence. We conducted an overview of reviews and included only reviews with a low risk of bias as assessed using the Risk of Bias in Systematic Reviews tool (ROBIS). We excluded any reviews where we found 100% overlap of included primary studies and selected systematic reviews or health technology assessments published after 2006 for inclusion.We performed an economic literature review of BNP and NT-proBNP testing in people with suspected heart failure. Medical and health economic databases were searched from database inception until July 25, 2019. Next, we assessed the cost-effectiveness of BNP and NT-proBNP based on the published economic literature. We transferred the cost-effectiveness results of two applicable, recent economic evaluations from the National Institute for Health and Care Excellence (NICE) to the Ontario setting in lieu of conducting de novo primary economic evaluations. We also estimated the budget impact of publicly funding BNP and NT-proBNP tests in people with suspected heart failure in Ontario over the next 5 years.To contextualize the potential value of BNP and NT-proBNP testing, we spoke with people with suspected heart failure.. We included eight systematic reviews in the clinical evidence review. B-type natriuretic peptides and NT-proBNP had a high pooled sensitivity (80% to 94% and 86% to 96%, respectively; strength of evidence: high) and a low pooled negative likelihood ratio (0.08-0.30 and 0.09-0.23, respectively; strength of evidence: not reported) within varying thresholds or cut points and settings, as reported in seven systematic reviews. In one systematic review, when BNP or NT-proBNP was used in the diagnosis of heart failure in the emergency department (ED), there was a decrease in the mean length of hospital stay (-1.22 days; confidence interval [CI] -2.31 to -0.14; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] Working Group criteria: Moderate). B-type natriuretic peptide testing did not reduce hospital admission rates (odds ratio [OR]: 0.82; CI: 0.67-1.01; GRADE: Moderate), 30-day hospital readmission rates (OR: 0.88; CI: 0.64-1,20; GRADE: Moderate), or hospital mortality rates (OR: 0.96; CI: 0.65-1.41; GRADE: Moderate). No systematic review was identified that addressed the impact on clinical outcomes of BNP use in the community setting.Our economic literature review found a total of 12 studies evaluating the cost-effectiveness of BNP or NT-proBNP testing in patients with suspected heart failure. The studies suggested that BNP or NT-proBNP tests, when used in addition to standard clinical investigations, were either dominant (less costly and more effective) or cost-effective across different countries (including Canada) and settings.Two economic evaluations conducted by NICE were considered applicable to our research question and of high methodological quality. Based on the transferred results from the two NICE economic evaluations, we concluded that BNP and NT-proBNP were highly likely to be cost-effective in Ontario in the ED setting, and NT-proBNP was highly likely to be cost-effective in the community care setting.Our budget impact analysis estimated that over the next 5 years, publicly funding BNP and NT-proBNP tests would result in an additional cost of $38 million in the ED (at a cost of $75 per test) and a cost savings of $20 million in community care (at a cost of $28 per test).We received strong support from interview participants about BNP or NT-proBNP diagnostic testing. The main reason was the perceived potential benefit of receiving a speedier diagnosis. The overall process, from diagnosis to treatment, is a substantial emo. B-type natriuretic peptide and NT-proBNP tests have high sensitivity and low negative likelihood ratio, suggesting that concentrations of either natriuretic peptides within the appropriate cut points can rule out the presence of heart failure with a high degree of confidence. Additionally, BNP or NT-proBNP testing along with usual care in an ED setting likely can reduce the length of hospital stay by at least 1 day but likely results in little to no difference in hospital mortality, 30-day readmission, or admission rates to hospital.Based on the published economic literature, we expected BNP or NT-proBNP tests used in addition to standard clinical investigations to be cost-effective as a rule-out test in patients with suspected heart failure in Ontario. If BNP and NT-proBNP tests are publicly funded in Ontario, we estimated that there would be additional costs in the ED setting (due to increased detection of heart failure) and savings in community care (due to reduced referrals to echocardiography and cardiologists).People we interviewed gave BNP and NT-proBNP testing strong support, citing the perceived benefits of quicker, more accurate diagnoses that could reduce misdiagnoses, stress, and the burden on patients and caregivers.

Topics: Adult; Diagnostic Tests, Routine; Heart Failure; Humans; Natriuretic Peptide, Brain; Ontario; Peptide Fragments; Systematic Reviews as Topic; Technology Assessment, Biomedical

B-type (or brain) natriuretic peptide (BNP) is synthesized in cardiac myocytes and released constitutively into the circulation. Pressure/volume overload, neurohumoral factors, cytokines, and ischemia enhance BNP gene expression, and then precursor proBNP is produced. It has been thought that proBNP is cleaved into active BNP molecule and inactive marker molecule NT-proBNP intracellularly by processing enzyme furin, and they are released into the circulation. However, recent studies have shown that considerable amount of uncleaved proBNP circulates in the blood. The commercially available BNP assay kits consist of two antibodies that sandwich the BNP molecule. Therefore, if proBNP is present, BNP assay kit cross-reacts to proBNP and measures it as BNP. Therefore, it should be noted that the current BNP value is proBNP plus BNP. BNP and NT-proBNP have been established as a biomarker for heart failure patients presenting dyspnea. But many pitfalls are present for interpreting the BNP value. For example, the presence of renal dysfunction, age, female sex, atrial fibrillation, inflammation, hyperthyroidism, use of sacubitril/valsartan, and macro-proBNPemia overestimate BNP value, whereas the presence of obesity, immediately after acute coronary syndrome onset, and pericardial effusion underestimate BNP value. In the management for heart failure patients, BNP plays an important role. Therefore, clinicians should note the pitfall of interpretation of BNP and we describe the mechanism involved.

Topics: Atrial Fibrillation; Biomarkers; Dyspnea; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments

Galectin-3 is a lectin that binds beta-galactosides. It is involved in cardiac remodeling and fibrosis through the activation of macrophages and fibroblasts. ST2 is secreted by myocardial cells due to cardiac overload. These two biomarkers have been traditionally studied in the field of heart failure to guide medical therapy and detect the progression of the disease. Nevertheless, there are novel evidences that connect galectin-3 and ST2 with coronary heart disease and, specifically, with atrial fibrillation. The aim of this article is to concisely review the diagnostic and prognostic role of galectin-3 and ST2 in different cardiac diseases.

Topics: Atrial Fibrillation; Biomarkers; Blood Proteins; Coronary Disease; Disease Progression; Fibroblasts; Galectins; Heart; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Macrophages; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Survival Analysis; Troponin

Transition from stage C to stage D of heart failure (HF) represents an irreversible process toward end-stage disease. Crucial interventions to be adopted in the attempt to interfere with this process are represented by the identification of patients at high risk to develop HF progression and by an effective and prompt management. Markers of worse prognosis and disease progression are well established and include recurrence of HF decompensation, intolerance to the neurohormonal standard pharmacological treatment, and resistance to loop diuretics. In addition, both NT-proBNP and sympathetic nervous system (SNS) overdrive are strong predictors of adverse clinical outcome and allow to identify high-risk HF patients even in the presence of mild symptoms. To counteract the deleterious effects of the SNS activation, new strategies such as a new drug combining angiotensin receptor and neprilysin inhibition and baroreceptor stimulation therapy (BAT) have been investigated. Inability to properly counteract the SNS overdrive leads to acute HF decompensation by different mechanisms. The leading ones are represented by the progressive sodium and water retention with fluid overload and by the blood volume redistribution between splanchnic and non-splanchnic regions. The correct understanding of these mechanisms, together with the availability of new therapeutic options such as peritoneal ultrafiltration, represent the rationale but not infrequently overlooked therapeutic options to improve congestion management in HF patients.

Topics: Angiotensin Receptor Antagonists; Biomarkers; Disease Progression; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Stroke Volume

Sudden cardiac death (SCD) is an unexpected death caused by a sudden loss of cardiac function, which is currently a global public health problem. Evaluation of the agonal cardiac function of the deceased is a quite important task for the diagnosis of SCD in forensic medicine. Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are currently considered as significant biomarkers for the diagnosis of heart failure in both clinical and forensic practices. To investigate the postmortem evaluation roles of postmortem BNP and NT-proBNP levels for SCD, the present study meta-analyzed eight related studies from Embase, Cochrane Library, PubMed, China Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Data. Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included literature, and the meta-analysis was performed by RevMan 5.3.5 software. Postmortem NT-proBNP in pericardial fluid showed higher levels in the SCD group than that of the non-SCD group with the weighted mean difference = 3665.74, 95% confidence interval: 1812.89-5518.59, and p = 0.0001. However, postmortem levels of BNP in pericardial fluid and NT-proBNP in serum revealed no statistical difference between SCD and non-SCD subjects. The results of present meta-analysis demonstrated that postmortem NT-proBNP in the pericardial fluid could be used as an ancillary indicator for evaluation of agonal cardiac function in forensic medicine.

Topics: Biomarkers; Death, Sudden, Cardiac; Forensic Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pericardial Fluid

Heart failure (HF) is a worldwide disease with high levels of morbidity and mortality. The pathogenesis of HF is complicated and involves imbalances in hormone and electrolyte. B-type natriuretic peptide (BNP) has served as a biomarker of HF severity, and in recent years, it has been used to treat the disease, thanks to its cardio-protective effects, such as diuresis, natriuresis, and vasodilatation. In stage C/D HF, symptoms are severe despite elevated BNP. Disturbances in Ca

Topics: Heart Failure; Humans; Myocardium; Natriuretic Peptide, Brain; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics: Heart Failure; Humans; Myocardial Infarction; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

Topics: Acute Disease; Heart Failure; Humans; Natriuretic Peptide, Brain

This study investigated the use of natriuretic peptides as inclusion criteria and to develop recommendations regarding their use. B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are commonly used as inclusion criteria for heart failure (HF) clinical trials, but no consensus exists regarding their optimal use for this purpose. A comprehensive search of the Aggregate Analysis of ClincalTrials.gov database identified 3,446 HF trials. Of these, 365 recently completed or ongoing HF clinical trials (10.6%) used either BNP or NT-proBNP as inclusion criteria. A panel of experts discussed current practices and a path forward for the use of natriuretic peptides as inclusion criteria for HF trials. Significant variations existed across trials regarding which natriuretic peptide and which cutoff value were used. Overall, 43% used both natriuretic peptides, 33% used only NT-proBNP, and 24% used only BNP in determining eligibility. Studies using BNP and NT-proBNP concentrations as inclusion criteria had higher cardiovascular event rates and higher concentrations for study entry and were generally associated with higher event rates. Areas of uncertainty included use in certain patient populations in which natriuretic peptides are historically lower (e.g., black patients, obese patients, patients with HF with preserved ejection fraction) or higher (older patients, patients with atrial fibrillation). This paper discusses best practices regarding use of BNP or NT-proBNP in clinical trials and identification of gaps in medical literature, including importance of documentation in ClinicalTrials.gov studies to inform future research efforts.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis; Stroke Volume

Heart failure (HF) management is challenging due to high clinical heterogeneity of this disease which makes patients responding differently to evidence-based standard therapy established by the current reductionist approach. Better understanding of the genetic and epigenetic interactions may clarify molecular signatures underlying maladaptive responses in HF, including metabolic shift, myocardial injury, fibrosis, and mitochondrial dysfunction. DNA methylation, histone modifications and micro-RNA (miRNAs) may be major epigenetic players in the pathogenesis of HF. DNA hypermethylation of the kruppel-like factor 15 (KLF15) gene plays a key role in switching the failing heart from oxidative to glycolytic metabolism. Moreover, hypomethylation at H3K9 promoter level of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes also leads to reactivation of fetal genes in man. The role of miRNAs has been investigated in HF patients undergoing heart transplantation, for whom miR-10a, miR-155, miR-31, and miR-92 may be putative useful prognostic biomarkers. Recently, higher RNA methylation levels have been observed in ischemic human hearts, opening the era of "epitranscriptome" in the pathogenesis of HF. Currently, hydralazine, statins, apabetalone, and omega-3 polyunsatured fatty acids (PUFA) are being tested in clinical trials to provide epigenetic-driven therapeutic interventions. Moreover, network-oriented analysis could advance current medical practice by focusing on protein-protein interactions (PPIs) perturbing the "cardiac" interactome. In this review, we provide an epigenetic map of maladaptive responses in HF patients. Furthermore, we propose the "EPi-transgeneratIonal network mOdeling for STratificatiOn of heaRt Morbidity" (EPIKO-STORM), a clinical research strategy offering novel opportunities to stratify the natural history of HF.

Topics: Epigenesis, Genetic; Heart Failure; Humans; Myocardium; Natriuretic Peptide, Brain; Phenotype; Precision Medicine; Stroke Volume

Current biomarkers allow diagnosing a wide array of pathological processes and evaluating effects of therapies and prognosis for cardiological patients. This review focuses on a possibility of using N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity 2 (sST2), galectin-3, and other biomarkers in patients with chronic heart failure for evaluating the risk of life-threatening ventricular tachyarrhythmias and sudden cardiac death.

Topics: Biomarkers; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Tachycardia

Investigations into the mixed muscle-secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones - the natriuretic peptides - referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Topics: Animals; Atrial Appendage; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Cyclic GMP; Diabetes Mellitus; Fibrosis; Gene Expression Regulation, Developmental; Heart Atria; Heart Failure; Humans; Hypertension; Lipid Metabolism; Metabolic Syndrome; Mice; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Processing, Post-Translational; Pulmonary Arterial Hypertension; Receptors, Guanylate Cyclase-Coupled; Secretory Vesicles; Ventricular Remodeling; Water-Electrolyte Balance

Natriuretic peptides (NP), especially B type (BNP) and its N-terminal pro-B type natriuretic peptide (NT-proBNP), have long been regarded as biomarkers of volume overload and tools to exclude heart failure in the general population. However, their role in end-stage kidney disease (ESKD) is less certain given that BNP and NT-proBNP are excreted by the kidney and so serum concentrations of NPs are nearly universally elevated compared to controls. Nevertheless, the accumulated evidence suggests thatserum concentrations of NPs in patients with ESKD show moderate or strong positive relationships with underlying heart disease, abnormal cardiac structure or function and mortality. Limited evidence also supports the role of BNP including NT-proBNP, ANP in some studies, rather than CNP or DNP in risk stratification among ESKD patients as well as the utility of BNP samplings pre- and post- hemodialysis. However, studies of the cut-off values of NPs have yielded inconsistent results, such that further large-scale studies are needed to clarify these issues. This review summarizes the pathophysiology and significance of NPs in ESKD patients, especially their potential role as risk stratification biomarkers in clinical management.

Topics: Biomarkers; Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis; Renal Dialysis; Risk Factors

As the heart matures during embryogenesis from its foetal stages, several structural and functional modifications take place to form the adult heart. This process of maturation is in large part due to an increased volume and work load of the heart to maintain proper circulation throughout the growing body. In recent years, it has been observed that these changes are reversed to some extent as a result of cardiac disease. The process by which this occurs has been characterized as cardiac foetal reprogramming and is defined as the suppression of adult and re-activation of a foetal genes profile in the diseased myocardium. The reasons as to why this process occurs in the diseased myocardium are unknown; however, it has been suggested to be an adaptive process to counteract deleterious events taking place during cardiac remodelling. Although still in its infancy, several studies have demonstrated that targeting foetal reprogramming in heart failure can lead to substantial improvement in cardiac functionality. This is highlighted by a recent study which found that by modulating the expression of 5-oxoprolinase (OPLAH, a novel cardiac foetal gene), cardiac function can be significantly improved in mice exposed to cardiac injury. Additionally, the utilization of angiotensin receptor neprilysin inhibitors (ARNI) has demonstrated clear benefits, providing important clinical proof that drugs that increase natriuretic peptide levels (part of the foetal gene programme) indeed improve heart failure outcomes. In this review, we will highlight the most important aspects of cardiac foetal reprogramming and will discuss whether this process is a cause or consequence of heart failure. Based on this, we will also explain how a deeper understanding of this process may result in the development of novel therapeutic strategies in heart failure.

Topics: Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Cardiovascular Agents; Cellular Reprogramming; Electrophysiological Phenomena; Heart Failure; Humans; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Neprilysin

Heart failure remains a continuing threat to patients with chronic kidney disease (CKD). Although various heart failure biomarkers have been applied for early detection, diagnosis and prognosis in CKD, these are easily affected by renal insufficiency thus limiting use in these patients. In this review, the major four groups of heart failure biomarkers are explored. These include those associated with: myocardial stretch, ie, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP); myocyte injury, ie, high-sensitivity troponin T (hsTnT), heart-type fatty acid-binding protein (H-FABP); fibrosis, matrix remodelling and inflammation, ie, soluble growth stimulating gene 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15); and renal function, ie, neutrophil gelatinase-associated lipocalin (NGAL) kidney injury molecule-1 (KIM-1), cystatin C (CysC), urinary sodium and urinary albumin. This review highlights classic heart failure biomarkers with critical values adjusted to glomerular filtration rate, summarizes research progress of new heart failure biomarkers and future research directions. Because diagnostic and prognostic usefulness of a single time point biomarker is limited, biomarkers should be combined and monitored at multiple times for optimal clinical impact.

Topics: Biomarkers; Glomerular Filtration Rate; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic

Describe the mechanisms that may influence change in measured natriuretic peptide levels when using the neprilysin inhibitor sacubitril to treat a patient with heart failure.. Prior to the introduction of the neprilysin inhibitor sacubitril as part of a chemical combination with the angiotensin receptor blocker valsartan shown to reduce mortality and heart failure hospitalizations in patients with heart failure with reduced ejection fraction, the natriuretic peptide assays for B-type natriuretic peptide (BNP) and the amino-terminal proBNP (NT-proBNP) assays were shown to have similar diagnostic accuracy to differentiate heart failure from other etiologies of shortness of breath. Sacubitril/valsartan use has been shown to result in a modest and chronic elevation of BNP while reducing levels of NT-prBNP. This review explores the potential impact of these findings on interpreting natriuretic peptide results for diagnosis and prognosis, as well as explore the challenges associated with the heterogeneity of this finding, highlighting the impact of inhibiting neprilysin, a non-specific endopeptidase with multiple target sites within BNP and other proteins. With increased uptake of sacubitril/valsartan expected in patients with heart failure, interpretation of natriuretic peptide assays becomes somewhat more complex, particularly for BNP. However, knowing a baseline steady-state concentration and using the same assay can assist with BNP interpretation for diagnosis and prognosis.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Drug Combinations; Heart Failure; Humans; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Tetrazoles

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors

Cardiogenic shock is difficult to diagnose due to diverse presentations, overlap with other shock states (i.e. sepsis), poorly understood pathophysiology, complex and multifactorial causes, and varied hemodynamic parameters. Despite advances in interventions, mortality in patients with cardiogenic shock remains high. Emergency clinicians must be ready to recognize and start appropriate therapy for cardiogenic shock early.. This review will discuss the clinical evaluation and diagnosis of cardiogenic shock in the emergency department with a focus on the emergency clinician.. The most common cause of cardiogenic shock is a myocardial infarction, though many causes exist. It is classically diagnosed by invasive hemodynamic measures, but the diagnosis can be made in the emergency department by clinical evaluation, diagnostic studies, and ultrasound. Early recognition and stabilization improve morbidity and mortality. This review will focus on identification of cardiogenic shock through clinical examination, laboratory studies, and point-of-care ultrasound.. The emergency clinician should use the clinical examination, laboratory studies, electrocardiogram, and point-of-care ultrasound to aid in the identification of cardiogenic shock. Cardiogenic shock has the potential for significant morbidity and mortality if not recognized early.

Topics: Acidosis, Lactic; Bradycardia; Confusion; Early Diagnosis; Echocardiography; Edema; Electrocardiography; Emergency Service, Hospital; Heart Failure; Heart Murmurs; Humans; Hypotension; Kidney Function Tests; Lactic Acid; Liver Function Tests; Multiple Organ Failure; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Physical Examination; Point-of-Care Systems; Pulmonary Edema; Shock, Cardiogenic; Tachycardia; Troponin

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

Natriuretic peptides are peptide hormones which are involved in the regulation of blood pressure, water-mineral balance and multiple metabolic processes. The beginning of research on this group of hormones starts in 1981, when the deBold and collaborators discovered ANP. Eight natriuretic peptides have been described so far: ANP, BNP, CNP, DNP, urodilatin, uroguanylin, osteocrin, musculin and three receptors: NPR-A, NPR-B and NPR-C thanks to which these hormones accomplish their physiological functions. Determination of natriuretic peptide concentration in plasma is used in the diagnosis and treatment of heart failure and pulmonary embolism. Research results indicate that the determination of natriuretic peptides concentration in plasma may also be important in the acute coronary syndromes, subclinical complications of hypertension and atrial fibrillation. The concentration of natriuretic peptides is changing in many diseases. The beneficial effects of natriuretic peptides have led to the production of drugs that are their synthetic derivatives. These drugs are mainly used among patients with heart failure. Research is currently underway on the efficacy and safety of other synthetic natriuretic peptides.

Topics: Blood Pressure; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Vasodilator Agents

The efficacy of baroreflex activation therapy for heart failure is elusive. This meta-analysis aims to evaluate the impact of baroreflex activation therapy on treatment efficacy of heart failure.. Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been searched, and we include randomized controlled trials (RCTs) regarding the efficacy of baroreflex activation therapy for patients with heart failure.. This meta-analysis includes 4 RCTs. Baroreflex activation therapy shows significantly positive impact on the quality of life score (standard mean difference SMD = -4.61; 95% confidence interval CI = -6.24 to -2.98; P < .00001), 6-minute hall walk (6MHW) distance (SMD = 2.83; 95% CI = 1.44- 4.22; P < .0001), New York Heart Association (NYHA) Class (SMD = -3.23; 95% CI = -4.76 to -1.69; P < .0001), N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD = -1.24; 95% CI = -1.58 to -0.89; P < .00001) and the duration of hospitalization (SMD = -1.65; 95% CI = -2.90 to -0.39; P = .01) compared with control group for heart failure, but has no obvious effect on left ventricular ejection fraction (LVEF) (SMD = 1.43; 95% CI = -0.15-3.01; P = .08), or the number of hospitalization per year (SMD = -1.17; 95% CI = -2.56-0.22; P = .10).. Baroreflex activation therapy can improve the treatment efficacy for heart failure.

Topics: Baroreflex; Electric Stimulation Therapy; Heart Failure; Humans; Implantable Neurostimulators; Length of Stay; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Randomized Controlled Trials as Topic; Walk Test

The safety and efficacy of Naoxintong Capsules combined with Western medicine in treatment of chronic heart failure(CHF) were analyzed based on Meta-analysis system. Databases, such as CNKI, VIP, WanFang, PubMed, EMbase and Cochrane Library, were retrieved from the inception to 31 August, 2019, to collect literatures about the effect of Naoxintong Capsules in treating CHF. RevMan 5.3 software provided by Cochrane collaboration network was used for statistical processing of the extracted data. This study included 15 RCTs, involving 1 595 patients, including 802 cases in the treatment group and 787 cases in the control group. The quality of the literatures was generally low. Meta-analysis results showed that the clinical efficacy rate on patients can be significantly improved by adding Naoxintong Capsules to conventional Western medicine, so as to significantly increase chronic heart failure(RR=1.24, 95%CI[1.18, 1.31], P<0.000 01), ventricular ejection fraction(MD=3.96, 95%CI[2.64, 5.27], P<0.000 01), left ventricular short axis shortening rate(MD=4.17, 95%CI[2.25, 6.10], P<0.000 1), and stroke volume(MD=10.27, 95%CI[8.47, 12.08], P<0.000 01), and reduce type B natriuretic peptide(MD=-50.10, 95%CI[-68.42,-31.78], P<0.000 01), left ventricular end-diastolic diameter(MD=-5.69, 95%CI[-7.68,-3.69], P<0.000 01), left ventricular end-systolic diameter(MD=-4.05, 95%CI[-4.89,-3.21], P<0.000 01) and left ventricular end-systolic volume(MD=-6.67, 95%CI[-8.46,-4.88], P<0.000 01), with statistically significant differences. Naoxintong Capsules combined with Western medicine can improve the clinical efficacy on patients with chronic heart failure, and cardiac function indexes and B-type natriuretic peptide levels.

Topics: Capsules; Drugs, Chinese Herbal; Heart Failure; Humans; Natriuretic Peptide, Brain

Heart failure (HF) is the most rapidly growing cardiovascular condition with an estimated prevalence of >37.7 million individuals globally. HF is associated with increased mortality and morbidity and confers a substantial burden, in terms of cost and quality of life, for the individuals and the healthcare systems, highlighting thus the need for early and accurate diagnosis of HF. The accuracy of HF diagnosis, severity estimation, and prediction of adverse events has improved by the utilization of blood tests measuring biomarkers. The contribution of biomarkers for HF management is intensified by the fact that they can be measured in short time at the point-of-care. This is allowed by the development of portable analytical devices, commonly known as point-of-care testing (POCT) devices, which exploit the advancements in the area of microfluidics and nanotechnology. The aim of this review paper is to present a review of POCT devices used for the measurement of biomarkers facilitating decision making when managing HF patients. The devices are either commercially available or in the form of prototypes under development. Both blood and saliva samples are considered. The challenges concerning the implementation of POCT devices and the barriers for their adoption in clinical practice are discussed.

Topics: Aged; Biomarkers; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Point-of-Care Testing; Quality of Life; Saliva

GUIDE-IT, the largest trial to date, published in August 2017, evaluating the effectiveness of natriuretic peptide (NP)-guided treatment of heart failure (HF), was stopped early for futility on a composite outcome. However, the reported effect sizes on individual outcomes of all-cause mortality and HF admissions are potentially clinically relevant.. This systematic review and meta-analysis aims to combine all available trial level evidence to determine if NP-guided treatment of HF reduces all-cause mortality and HF admissions in patients with HF.. Eight databases, no language restrictions, up to November 2017 were searched for all randomised controlled trials comparing NP-guided treatment versus clinical assessment alone in adult patients with HF. No language restrictions were applied. Publications were independently double screened and extracted. Fixed-effect meta-analyses were conducted.. 89 papers were included, reporting 19 trials (4554 participants), average ages 62-80 years. Pooled risk ratio estimates for all-cause mortality (16 trials, 4063 participants) were 0.87, 95% CI 0.77 to 0.99 and 0.80, 95% CI 0.72 to 0.89 for HF admissions (11 trials, 2822 participants). Sensitivity analyses, restricted to low risk of bias, produced similar estimates, but were no longer statistically significant.. Considering all the evidence to date, the pooled effects suggest that NP-guided treatment is beneficial in reducing HF admissions and all-cause mortality. However, there is still insufficient high-quality evidence to make definitive recommendations on the use of NP-guided treatment in clinical practice.. Systematic Review Cochrane Database Number: CD008966.

Topics: Cause of Death; Evidence-Based Medicine; Heart Failure; Hospitalization; Humans; Medical Futility; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Area Under Curve; Atrial Natriuretic Factor; Biomarkers; Databases, Factual; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve

Heart failure is a class of cardiovascular diseases that remains the number one cause of death worldwide with a substantial economic burden of around $18 billion incurred by the healthcare sector in 2017 due to heart failure hospitalization and disease management. Although several laboratory tests have been used for early detection of heart failure, these traditional diagnostic methods still fail to effectively guide clinical decisions, prognosis, and therapy in a timely and cost-effective manner. Recent advances in the design and development of biosensors coupled with the discovery of new clinically relevant cardiac biomarkers are paving the way for breakthroughs in heart failure management. Natriuretic neurohormone peptides, B-type natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP), are among the most promising biomarkers for clinical use. Remarkably, they result in an increased diagnostic accuracy of around 80% owing to the strong correlation between their circulating concentrations and different heart failure events. The latter has encouraged research towards developing and optimizing BNP biosensors for rapid and highly sensitive detection in the scope of point-of-care testing. This review sheds light on the advances in BNP and NT-proBNP sensing technologies for point-of-care (POC) applications and highlights the challenges of potential integration of these technologies in the clinic. Optical and electrochemical immunosensors are currently used for BNP sensing. The performance metrics of these biosensors-expressed in terms of sensitivity, selectivity, reproducibility, and other criteria-are compared to those of traditional diagnostic techniques, and the clinical applicability of these biosensors is assessed for their potential integration in point-of-care diagnostic platforms.

Topics: Biomarkers; Biosensing Techniques; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Point-of-Care Systems

The efficacy of liraglutide to treat heart failure remains controversial. We conducted a systematic review and meta-analysis to explore the influence of liraglutide on heart failure.. We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases through March 2018 for randomized controlled trials (RCTs) assessing the effect of liraglutide on cardiac function of heart failure. Meta-analysis is performed using the random-effect model.. Four RCTs involving 629 patients are included in the meta-analysis. Overall, compared with the control group for heart failure, liraglutide treatment significantly can reduce NT-proBNP (Std. MD = -3.06; 95% CI = -5.78 to -0.34; P = .03), and improve 6MWT (Std. MD=1.10; 95% CI = 0.75 to 1.44; P < .00001), but has no remarkable influence on LVEF change (Std. MD=1.10; 95% CI = -1.97 to 3.98; P = 0.51), LVEDV change (Std. MD = 6.26; 95% CI = -1.45 to 13.97; P = .11), LVESV change (Std. MD = -13.47; 95% CI = -31.04 to 4.10; P = .13), hospitalization for heart failure (RR = 1.18; 95% CI = 0.88 to 1.58; P = .27), major adverse cardiovascular events (RR = 1.55; 95% CI = -0.24 to 9.89; P = .64), and cardiac death (RR = 1.11; 95% CI = 0.61 to 2.04; P = .72).. Liraglutide treatment has an important ability to reduce NT-proBNP and improve 6MWT for heart failure, but shows no important influence on LVEF, LVEDV, LVESV, hospitalization for heart failure, major adverse cardiovascular events, and cardiac death.

Topics: Blood Pressure; Cardiovascular Agents; Heart Failure; Hospitalization; Humans; Liraglutide; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Stroke Volume; Walk Test

This review focuses on possibilities of using soluble ST2 as a HF marker for diagnostics, stratification of risk of adverse events, and for evaluation of prognosis and treatment effectiveness in patients with CHF. Circulating biomarkers are an essential element of algorithms for diagnostics, stratification of risk, and evaluation of prognosis in patients with HF. The recognized "gold standard", natriuretic peptides, has several well-known limitations, and multiple new candidate biomarkers have appeared in recent years. Soluble ST2, a marker of "mechanical myocardial stress", is considered as one of the most promising new biomarkers. This review discusses possibilities of using it in clinical practice in CHF patients.

Topics: Biomarkers; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Prognosis; Receptors, Cell Surface; Risk Assessment

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Among these, ANP and BNP are secreted by the heart and act as cardiac hormones. Both ANP and BNP preferentially bind to natriuretic peptide receptor-A (NPR-A or guanylyl cyslase-A) and exert similar effects through increases in intracellular cyclic guanosine monophosphate (cGMP) within target tissues. Expression and secretion of ANP and BNP are stimulated by various factors and are regulated via multiple signaling pathways. Human ANP has three molecular forms, α-ANP, β-ANP, and proANP (or γ-ANP), with proANP predominating in healthy atrial tissue. During secretion proANP is proteolytically processed by corin, resulting in secretion of bioactive α-ANP into the peripheral circulation. ProANP and β-ANP are minor forms in the circulation but are increased in patients with heart failure. The human BNP precursor proBNP is proteolytically processed to BNP

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptides; Protein Processing, Post-Translational

Obesity is a major risk factor for the development of chronic heart failure (CHF) and does not only pose diagnostic challenges, but also has prognostic implications for these patients. Paradoxically, obese patients with CHF have a better prognosis than thinner individuals. In recent years, it has been demonstrated that the adipose tissue, even in patients with HF, is not always detrimental, and that obesity may coexist with a phenotype of benign adiposity without systemic metabolic abnormalities. Experimental data have shown that natriuretic peptides (NPs), and in particular brain natriuretic peptide (BNP), play a major role in the communication of the heart with the adipose tissue. Body fat distribution and adipose tissue function show a large degree of heterogeneity among depots and may explain the complex relationship between NPs and body fat. NPs can affect both the quality and the behaviour of fatty tissue, promoting a healthy adipocyte phenotype, and can favourably affect body fat metabolism. In this article, we review the existing literature on the bidirectional effects of BNP and adipose tissue in HF and highlight the complexity of this relationship.

Topics: Adipose Tissue; Adiposity; Body Fat Distribution; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Phenotype; Prevalence; Prognosis; Risk Factors

Heart failure with reduced ejection fraction (HFrEF) represents a significant public health burden associated with incremental health care costs. Given the limitations associated with pharmacological autonomic regulation therapy (ART), device-based autonomic neuromodulation is on the horizon now for ART in those patients. This systematic review aimed primarily to determine the effect of ART by devices on functional status and quality of life (QOL) in patients with HFrEF. We performed a meta-analysis of five randomized controlled trials (1074 patients) comparing ART by devices versus optimal medical therapy (OMT) in HFrEF. We assessed pooled estimates of odds ratio (OR) for improvement in New York Heart Association (NYHA) class and mean differences (MD) in 6-minute hall walk distance (6-MHWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and left ventricular end-systolic volume index (LVESVi) with their 95% confidence intervals (CIs) at 6-month follow-up. Compared to OMT alone, ART by devices in HFrEF significantly improves NYHA class (OR 2.26, 95% CI 1.33 to 3.83, P = 0.003), increases 6-MHWD (MD 45.53 m, 95% CI 30.61 to 60.45, P < 0.00001), improves MLHFQ score (MD - 10.59, 95% CI - 20.62 to - 0.57, P = 0.04) with neutral effect on NT-proBNP levels (MD - 236.5 pg/ml, 95% CI - 523.86 to 50.87, P = 0.11) and LVESVi (MD - 1.01 ml/m

Topics: Adult; Aged; Autonomic Nervous System; Female; Health Care Costs; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome; Vagus Nerve Stimulation; Ventricular Function, Left; Walk Test

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

B-type natriuretic peptide (BNP) is a circulating biomarker that is mainly applied in heart failure (HF) diagnosis and to monitor disease progression. Because some identical amino acid sequences occur in the precursor and metabolites of BNP, undesirable cross-reactions are common in immunoassays. This review first summarizes current analytical methods, such as immunoassay- and mass spectrometry (MS)-based approaches, including the accuracy of measurement and the inconsistency of the results. Second, the review presents some promising approaches to resolve the current barriers in clinical BNP measurement, such as how to decrease cross-reactions and increase the measurement consistency. Specific approaches include research on novel BNP assays with higher-specificity chemical antibodies, the development of International System of Units (SI)-traceable reference materials, and the development of structure characterization methods based on state-of-the-art ambient and ion mobility MS technologies. The factors that could affect MS analysis are also discussed, such as biological sample cleanup and peptide ionization efficiency. The purpose of this review is to explore and identify the main problems in BNP clinical measurement and to present three types of approaches to resolve these problems, namely, materials, methods and instruments. Although novel approaches are proposed here, in practice, it is worth noting that the BNP-related peptides including unprocessed proBNP were all measured in clinical BNP assays. Therefore, approaches that aimed to measure a specific BNP or proBNP might be an effective way for the standardization of a particular BNP form measurement, instead of the standardization of "total" immunoreactive BNP assays in clinical at present.

Topics: Biomarkers; Heart Failure; Humans; Mass Spectrometry; Natriuretic Peptide, Brain

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

The 2017 focused update of the 2013 ACC/AHA guideline on heart failure contains new and important recommendations on prevention, novel biomarker uses, heart failure with preserved ejection fraction (HFpEF), and comorbidities such as hypertension, iron deficiency, and sleep-disordered breathing. Potential implications for management of acute decompensated heart failure will also be explored.

Topics: Biomarkers; Blood Pressure; Cardiology; Disease Management; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Referral and Consultation; Stroke Volume

Heart failure (HF) is a clinical syndrome that associates clinical signs in people over 80 years of age, an increase in natriuretic peptides and abnormal cardiac structures that result from cardiac aging in many cases. The most common symptoms are grouped according to the acronym "EPOF" (shortness of breath, weight gain, edema, fatigue). Over the age of 80, comorbidities must be taken into account. The incidence and prevalence of HF significantly increases with age and makes HF the most common reason for hospitalization for people over 80, and an important health expense. The management of HF, necessarily multidisciplinary with a geriatric evaluation, has improved over time due to effective targeted treatment, but mortality, hospitalization and readmission rates remain high. Therapeutic education and patient follow-up for treatment optimization are needed.

Topics: Aged, 80 and over; Aging; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Heart; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Patient Education as Topic; Peptide Fragments; Prognosis

Topics: Arrhythmias, Cardiac; Electrocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is useful in diagnosis and prognostication in heart failure (HF). We examined the relationship between NT-proBNP and outcomes in patients with HF and preserved ejection fraction, with and without atrial fibrillation (AF). Methods and Results Among 3835 HF with preserved ejection fraction patients enrolled in the I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function trial) or TOPCAT trial (Treatment of Preserved Cardiac Function in Heart Failure With an Aldosterone Antagonist), 719 (19%) patients had AF on their baseline ECG. Median (Q1-Q3) levels of NT-proBNP were 1286 pg/mL (778-2072) in those with AF and 288 pg/mL (122-704) in those without ( P<0.001). We analyzed patients using 4 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, and ≥2000 pg/mL. The event rates for the primary composite outcome of cardiovascular death or HF hospitalization were higher in patients with AF versus patients without or those without without AF in the lowest NT-proBNP band (<400 pg/mL; 8.0 versus 3.2 per 100 patient-years), whereas for the higher bands the opposite was true (1000-1999 pg/mL; 11.4 versus 13.2 per 100 patient-years and ≥2000 pg/mL; 17.4 versus 25.6 per 100 patient-years). In adjusted analyses, higher NT-proBNP levels were less predictive of HF hospitalization than mortality in patients with AF compared with those without. Conclusions Event rates in HF with preserved ejection fraction patients without AF and with NT-proBNP <400 pg/mL are low. Among patients with NT-proBNP ≥400 pg/mL, the relationship between NT-proBNP and outcomes differs with lower absolute risk in patients who have AF compared with those who do not have AF. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00094302 and NCT00095238.

Topics: Aged; Atrial Fibrillation; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Stroke Volume

To assess whether natriuretic peptides (NPs) can be used to reliably predict long-term therapeutic effect on clinical outcomes for patients with heart failure and reduced ejection fraction (HFrEF).. HFrEF intervention trials with mortality data were identified. Subsequently, we identified trials assessing therapy-induced changes in NPs. We assessed the correlation between the average short-term placebo-corrected drug or device effect on NPs and the longer-term therapeutic effect on clinical outcomes. Of 35 distinct therapies with an identifiable mortality result (n = 105 062 patients), 20 therapies had corresponding data on therapeutic effect on NPs. No correlation was observed between therapy-induced placebo-corrected change in brain natriuretic peptide or N-terminal pro-brain natriuretic peptide and therapeutic effect on all-cause mortality (ACM) (Spearman r = -0.32, P = 0.18 and r = -0.20, P = 0.47, respectively). There was no correlation between therapy-induced placebo-corrected per cent change in NP and intervention effect on ACM or ACM-heart failure hospitalizations (r = -0.30, P = 0.11 and r = 0.10, P = 0.75, respectively).. Short-term intervention-induced changes in NP levels are not reliable predictors of therapeutic long-term effect on mortality or morbidity outcomes for patients with HFrEF.

Topics: Biomarkers; Cardiovascular Diseases; Cause of Death; Heart Failure; Hospitalization; Humans; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume

Recent studies have shown the efficacy for using spironolactone to treat heart failure with reduced ejection fraction (HFrEF), but the efficacy of spironolactone for heart failure with mid-range ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) is unclear. This meta-analysis investigated the efficacy and safety of spironolactone in patients with HFmrEF and HFpEF.. We searched several databases including PubMed and the Cochrane Collaboration, for randomized controlled trials (RCTs) that assessed spironolactone treatment in HFmrEF and HFpEF. Eleven RCTs including 4539 patients were included. Spironolactone reduced hospitalizations (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73-0.95; P = .006), improved New York Heart Association functional classifications (NYHA-FC) (OR, 0.35; 95% CI, 0.19-0.66; P = .001), decreased the levels of brain natriuretic peptide (BNP) (mean difference [MD], - 44.80 pg/mL; 95% CI, -73.44--16.17; P = .002), procollagen type I C-terminal propeptide (PICP) (MD, -27.04 ng/mL; 95% CI, -40.77--13.32, P < .001) in HFmrEF and HFpEF. Besides, it improved 6-minute walking distances (6-MWD) (standard weighted mean difference [SMD], 0.45 m; 95% CI, 0.27-0.64; P < .001), decreased amino-terminal peptide of procollagen type-III (PIIINP) (SMD, -0.37 μg/L; 95% CI, -0.59--0.15; P = .001) in HFpEF only. The risks of hyperkalemia (P<.001) and gynecomastia (P<.001) were increased.. Patients with HFmrEF and HFpEF could benefit from spironolactone treatment, with reduced hospitalizations, BNP levels, improved NYHA-FC, alleviated myocardial fibrosis by decreasing serum PICP in HFmrEF and HFpEF, decreased PIIINP levels and increased 6-MWD only in HFpEF. The risks of hyperkalemia and gynecomastia were significantly increased with the spironolactone treatment.

Topics: Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Randomized Controlled Trials as Topic; Risk Factors; Spironolactone; Stroke Volume; Walking Speed

Currently, brain natriuretic peptide (BNP) and

Topics: Animals; Biomarkers; Diagnosis; Forensic Medicine; Gene Expression Regulation; Heart Failure; Heart Function Tests; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proteolysis; Severity of Illness Index; Signal Transduction; Translational Research, Biomedical

The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P < 0.01). This network meta-analysis is the first to find that finerenone 7.5-10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%.

Topics: Eplerenone; Heart Failure; Hospitalization; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Peptide, Brain; Network Meta-Analysis; Peptide Fragments; Randomized Controlled Trials as Topic; Renal Insufficiency; Spironolactone; Treatment Outcome

Biomarkers may help to rapidly differentiate heart failure from noncardiac causes of acute dyspnea. Natriuretic peptides are especially useful for this purpose and should be measured in all patients presenting with acute onset dyspnea. Due to their excellent negative predictive value, a normal serum concentration of natriuretic peptides makes acute heart failure unlikely. Assays exist for B‑type natriuretic peptide (BNP), N‑terminal pro-B-type natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) with established cut-offs in the acute setting. Importantly, in patients treated with an angiotensin receptor-neprilysin inhibitor (ARNI), NT-proBNP (or MR-proANP) should be used instead of BNP, since the latter is increased by ARNI treatment. Besides their established diagnostic value in heart failure patients, the measurement of natriuretic peptides provides prognostic information and may help in guiding therapy. Additionally, multiple other biomarkers reflect several pathophysiological processes involved in heart failure patients. Their diagnostic and prognostic impact in heart failure needs to be established.

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

To evaluate the effectiveness and safety of oral Chinese herbal medicine (OCHM) for heart failure with preserved ejection fraction (HFpEF).. PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Chinese Biological Medicine Database (CBM), Wanfang Database, Chongqing VIP Information (VIP) and China National Knowledge Infrastructure (CNKI) were searched for appropriate articles from respective inceptions until June 3, 2018. Randomized controlled trials (RCTs) investigating the effectiveness of OCHM for the patients with HFpEF were eligible. Quality assessment was performed by employing the Cochrane Risk of Bias assessment tool. Papers were independently reviewed by two reviewers and analyzed using Cochrane software Revman 5.3. Dichotomous data were analyzed by relative risk (RR) with a 95% confidence interval (CI), while continuous variables were analyzed by using mean difference (MD) with 95% CI for effect size.. A total of 16 RCTs involving 1,320 participants were identified. Fourteen of the trials used conventional Western medicine (CWM) as the control, the control of 1 trial was no treatment, and another was placebo. Three of the trials served Chinese patent medicine (CPM) as interventions, and other OCHM were Chinese medicine decoctions (CMDs). Only limited evidence showed experimental group with OCHM may get better effect on brain natriuretic peptide (BNP: MD -37.29, 95% CI -53.08 to -21.50, P<0.00001) or N terminal pro B type natriuretic peptide (NT-proBNP: MD -236.04, 95% CI -356.83 to -115.25, P=0.0001), Minnesota Living with Heart Failure questionnaire (MLHFQ, MD -9.94, 95% CI -16.77 to -3.11, P=0.004), but the results had high heterogeneities. With concerns on 12 of 16 trials, the meta-analysis found that the adjuvant therapy of OCHM might be more effective in increasing overall response rate (RR 1.17, 95% CI 1.11 to 1.24, P<0.00001), when compared with CWM alone. Subgroup meta-analysis between CPMs and CMDs showed that the two CPMs may have more therapeutic effect on MLHFQ, but not on NT-proBNP, and CMD came to the opposite conclusion. No significant differences were found between experimental groups and control groups on 6-min walk test (6MWT). Adverse events, such as more defecation, weakness, cardiopalmus, edema, cough and hypotension, were mild in all groups and disappeared after the easement of pharmacological intervention.. Due to the insufficient quality of trials that were analyzed, it is not appropriate to confirm or deny the potency of OCHMs in treating HFpEF at the present time. More rigorously designed RCTs focusing on primary endpoints with long-term follow-up are warranted to validate the effect of OCHMs for patients with HFpEF.

Topics: Administration, Oral; Drugs, Chinese Herbal; Heart Failure; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Stroke Volume; Surveys and Questionnaires

Heart failure (HF) is a growing challenge in the Asia Pacific region. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established tool for diagnosis of HF; however, it is relatively underutilized in predicting adverse outcomes in HF. Multiple studies have demonstrated the prognostic role of NT-proBNP in HF. A single value of NT-proBNP >5000 pg/mL predicts a worse outcome in hospitalized patients with HF with reduced ejection fraction (HFrEF). In stable outpatients with HFrEF, NT-proBNP > 1000 pg/mL predicts a poorer prognosis. NT-proBNP provides the same prognostic information in patients with HF with preserved ejection fraction (HFpEF) as in those with HFrEF. An expert panel composed of cardiologists mainly from Asia Pacific region was convened to discuss the utility of NT-proBNP in HF prognostication. This article summarizes available scientific evidence and consensus recommendations from the meeting.

Topics: Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume

Natriuretic peptide [NP; B-type NP (BNP), N-terminal proBNP (NT-proBNP), and midregional proANP (MR-proANP)] concentrations are quantitative plasma biomarkers for the presence and severity of haemodynamic cardiac stress and heart failure (HF). End-diastolic wall stress, intracardiac filling pressures, and intracardiac volumes seem to be the dominant triggers. This paper details the most important indications for NPs and highlights 11 key principles underlying their clinical use shown below. NPs should always be used in conjunction with all other clinical information. NPs are reasonable surrogates for intracardiac volumes and filling pressures. NPs should be measured in all patients presenting with symptoms suggestive of HF such as dyspnoea and/or fatigue, as their use facilitates the early diagnosis and risk stratification of HF. NPs have very high diagnostic accuracy in discriminating HF from other causes of dyspnoea: the higher the NP, the higher the likelihood that dyspnoea is caused by HF. Optimal NP cut-off concentrations for the diagnosis of acute HF (very high filling pressures) in patients presenting to the emergency department with acute dyspnoea are higher compared with those used in the diagnosis of chronic HF in patients with dyspnoea on exertion (mild increase in filling pressures at rest). Obese patients have lower NP concentrations, mandating the use of lower cut-off concentrations (about 50% lower). In stable HF patients, but also in patients with other cardiac disorders such as myocardial infarction, valvular heart disease, atrial fibrillation or pulmonary embolism, NP concentrations have high prognostic accuracy for death and HF hospitalization. Screening with NPs for the early detection of relevant cardiac disease including left ventricular systolic dysfunction in patients with cardiovascular risk factors may help to identify patients at increased risk, therefore allowing targeted preventive measures to prevent HF. BNP, NT-proBNP and MR-proANP have comparable diagnostic and prognostic accuracy. In patients with shock, NPs cannot be used to identify cause (e.g. cardiogenic vs. septic shock), but remain prognostic. NPs cannot identify the underlying cause of HF and, therefore, if elevated, must always be used in conjunction with cardiac imaging.

Topics: Biomarkers; Cardiology; Europe; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Prognosis; Societies, Medical

Topics: Atrial Natriuretic Factor; Female; Heart; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor

Point-of-care tests (POCT) can assist general practitioners (GPs) in diagnosing and treating patients with acute cardiopulmonary symptoms, but it is currently unknown if POCT impact relevant clinical outcomes in these patients.. To assess whether using POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and impacts clinical management.. We performed a systematic review in four bibliographic databases. Articles published before February 2016 were screened by two reviewers. Studies evaluating the effect of GP use of POCT on clinical diagnostic accuracy and/or effect on treatment and referral rate in patients with cardiopulmonary symptoms were included.. Our search yielded nine papers describing data from seven studies, on the clinical diagnostic accuracy of POCT in a total of 2277 primary care patients with acute cardiopulmonary symptoms. Four papers showed data on GP use of D-dimer POCT in pulmonary embolism (two studies); two studies on Troponin T in acute coronary syndrome; one on heart-type fatty acid-binding protein (H-FABP) in acute coronary syndrome; one on B-type natriuretic peptide (BNP) in heart failure; one on 3-in-1 POCT (Troponin T, BNP, D-dimer) in acute coronary syndrome, heart failure and/or pulmonary embolism. Only one study assessed the effect of GP use of POCT on treatment initiation and one on actual referral rates.. There is currently limited and inconclusive evidence that actual GP use of POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and affects clinical management. However, some studies show promising results, especially when a POCT is combined with a clinical decision rule.

Topics: Acute Coronary Syndrome; Acute Disease; Biomarkers; Fibrin Fibrinogen Degradation Products; Heart Failure; Humans; Natriuretic Peptide, Brain; Point-of-Care Testing; Primary Health Care; Pulmonary Embolism; Randomized Controlled Trials as Topic; Troponin T

The natriuretic peptides play a vital role in normal physiology and as counter-regulatory hormones in heart failure (HF). Clinical assessment of their levels (for B-type natriuretic peptide [BNP], N-terminal proBNP, and the midregion of N-terminal pro-atrial natriuretic peptide) have become valuable tools in diagnosing patients with HF as well as risk stratifying and guiding therapy. Their roles have further expanded beyond HF to other cardiovascular conditions and for risk stratification in asymptomatic individuals. Understanding the clinical use of these hormones is vital to achieving their full potential.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a guideline-mandated biomarker in heart failure (HF). Used as an inclusion criterion for therapeutic trials, NT-proBNP enriches trial populations and is a valid surrogate endpoint. Its diagnostic performance is best validated in acute decompensated HF (ADHF). NT-proBNP offers prognostic information independent of standard clinical predictors and refines risk stratification. With the advent of combined angiotensin 2 type 1 receptor blockade and neprilysin inhibition (ARNI) NT-proBNP retains its relationship to cardiac status and is the marker of choice in assessment of possible ADHF and in serial monitoring of HF patients receiving ARNI treatment.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors

Congestion is one of the main predictors of poor patient outcome in patients with heart failure. However, congestion is difficult to assess, especially when symptoms are mild. Although numerous clinical scores, imaging tools, and biological tests are available to assist physicians in ascertaining and quantifying congestion, not all are appropriate for use in all stages of patient management. In recent years, multidisciplinary management in the community has become increasingly important to prevent heart failure hospitalizations. Electronic alert systems and communication platforms are emerging that could be used to facilitate patient home monitoring that identifies congestion from heart failure decompensation at an earlier stage. This paper describes the role of congestion detection methods at key stages of patient care: pre-admission, admission to the emergency department, in-hospital management, and lastly, discharge and continued monitoring in the community. The multidisciplinary working group, which consisted of cardiologists, emergency physicians, and a nephrologist with both clinical and research backgrounds, reviewed the current literature regarding the various scores, tools, and tests to detect and quantify congestion. This paper describes the role of each tool at key stages of patient care and discusses the advantages of telemedicine as a means of providing true integrated patient care.

Topics: Aftercare; Disease Progression; Dyspnea; Echocardiography; Edema, Cardiac; Emergency Medical Services; Emergency Service, Hospital; Heart Failure; Hospitalization; Humans; Lung; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Plasma Volume; Prognosis; Pulmonary Edema; Telemedicine; Vena Cava, Inferior; Water-Electrolyte Balance; Weight Gain

Adequate assessment of fluid status is an imperative objective in the management of all types of patients in cardiology, intensive care, and especially nephrology. Fluid overload is one of the most common modifiable risk factors directly associated with hypertension, heart failure, left ventricular hypertrophy, and eventually, higher morbidity and mortality risk in these categories of patients. Different methods are commonly used to determine fluid status (eg, clinical assessment, natriuretic peptide concentrations, echocardiography, inferior vena cava measurements, or bioimpedance analysis). In recent years, lung ultrasonography (LUS), through the assessment of extravascular lung water, has received growing attention in clinical research. This article summarizes available studies that compare LUS with other methods for fluid status assessment in patients with kidney diseases. At the same time, it also presents the association of LUS with different outcomes (physical functioning, mortality, and cardiovascular events) in the same population. It appears that this simple bedside noninvasive technique has significant clinical potential in nephrology.

Topics: Aged; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema; Renal Dialysis; Risk Assessment; Survival Rate; Treatment Outcome; Ultrasonography, Doppler; Water-Electrolyte Imbalance

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Disease Management; Drug Combinations; Heart Failure; Humans; Natriuretic Peptide, Brain; Signal Transduction; Stroke Volume; Tetrazoles; Valsartan

The results of several recent experimental studies using animal models and clinical trials suggested that obesity is not merely an epiphenomenon or a prominent comorbidity in patients with heart failure (HF). Indeed, recent studies suggest that obesity is intimately involved in the pathogenesis of HF with preserved ejection fraction (HFpEF). The most recent studies indicate that approximately 50% of HF patients have HFpEF. As standard pharmacological treatment usually shows only a weak or even neutral effect on primary outcomes in patients with HFpEF, treatment strategies targeted to specific groups of HFpEF patients, such as those with obesity, may increase the likelihood of reaching substantial clinical benefit. Considering the well-known inverse relationship between body mass index (BMI) values and B-type natriuretic peptide (BNP) levels, it is theoretically conceivable that the measurement of natriuretic peptides, using cutoff values adjusted for age and BMI, should increase diagnostic and prognostic accuracy in HFpEF patients. However, further experimental studies and clinical trials are needed to differentiate and better understand specific mechanisms of the various HFpEF phenotypes, including obese HFpEF.

Topics: Body Mass Index; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Phenotype; Stroke Volume

Natriuretic peptides (NPs) are recommended by international guidelines to exclude non-heart failure causes of acute dyspnea and to assess prognosis. NPs are commonly used as an entry criterion for clinical trials, to minimize enrollment of misdiagnosed patients, or to ensure enrollment of a sufficiently at-risk population. NP values used to select trial populations to date have been inconsistent across studies. Future trials should consider using standardized thresholds for NP levels, with protocol-specified adaptations appropriate for the specific study and patient population to account for factors that can influence the NP level. NPs have been used as an endpoint for proof-of-concept or phase 2 clinical trials, although it is important to remember that positive results in early phase studies may be unstable due to small numbers and the play of chance, and they are not always reproducible in phase 3 trials. Likewise, failure to reduce NP in phase 2 may not necessarily indicate that a drug will be ineffective on clinical outcomes in phase 3. NP guided therapy has been intensively studied, but the clinical outcome benefits of this approach remain uncertain. Neprilysin inhibitors have stimulated further exploration of the NP system and how it influences, and is potentially influenced by, heart failure therapies. This paper discusses the utility of NPs in the current clinical research and practice environment and addresses areas in need of further research from the perspectives of academic clinical trialists, clinicians, biostatisticians, regulators, and pharmaceutical industry scientists who participated in the 13th Global Cardiovascular Clinical Trialists Forum.

Topics: Biomarkers; Clinical Trials as Topic; Congresses as Topic; District of Columbia; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Patient Care

Biomarker-guided management of patients with chronic heart failure with reduced ejection fraction (HFrEF) remains controversial.. Biomarkers have established roles for diagnosis and prognostication in HF. Pilot data suggested that use of natriuretic peptides might be helpful to guide HF care. The recent Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) randomized-controlled trial did not find therapy guided by NT-proBNP to be more effective than usual care in improving the primary endpoint of HF hospitalization or cardiovascular mortality amongst patients with chronic HFrEF. Patients in GUIDE-IT received similar care and had similar NT-proBNP lowering regardless of treatment allocation. Though biomarkers retain important standing for diagnosis and prognosis in HF, the GUIDE-IT trial results suggest carefully managed patients may not benefit from a biomarker-guided strategy. Future studies focusing this intervention on patients treated in a more real-world setting are needed.

Topics: Biomarkers; Clinical Trials as Topic; Disease Management; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial. Moreover, BNP was shown to inhibit SERCA2a expression. Therefore, it is possible that high BNP levels interact with treatment effects of SERCA2a gene transfer and accordingly lead to negative results of CUPID 2 trial. From this point of view, effects of SERCA2a gene therapy should be explored in heart failure with preserved ejection fraction, which is characterised by lower BNP levels compared with HFrEF. In this review, we summarise the current knowledge of SERCA2a gene therapy for heart failure, analyse potential interaction between BNP levels and therapeutic effects of SERCA2a gene transfer and provide directions for future research to solve the identified problems.

Topics: Calcium Signaling; Clinical Trials as Topic; Genetic Therapy; Heart Failure; Humans; Natriuretic Peptide, Brain; Sarcoplasmic Reticulum Calcium-Transporting ATPases

Heart failure (HF) often coexists in atrial fibrillation (AF) but is frequently unrecognised due to overlapping symptomatology. Furthermore, AF can cause elevated natriuretic peptide levels, impairing its diagnostic value for HF detection. We aimed to assess the prevalence of previously unknown HF in community-dwelling patients with AF, and to determine the diagnostic value of the amino-terminal pro B-type natriuretic peptide (NTproBNP) for HF screening in patients with AF.. Individual participant data from four HF-screening studies in older community-dwelling persons were combined. Presence or absence of HF was in each study established by an expert panel following the criteria of the European Society of Cardiology. We performed a two-stage patient-level meta-analysis to calculate traditional diagnostic indices.. Of the 1941 individuals included in the four studies, 196 (10.1%) had AF at baseline. HF was uncovered in 83 (43%) of these 196 patients with AF, versus 381 (19.7%) in those without AF at baseline. Median NTproBNP levels of patients with AF with and without HF were 744 pg/mL and 211 pg/mL, respectively. At the cut-point of 125 pg/mL, sensitivity was 93%, specificity 35%, and positive and negative predictive values 51% and 86%, respectively. Only 23% of all patients with AF had an NTproBNP level below the 125 pg/mL cut-point, with still a 13% prevalence of HF in this group.. With a prevalence of nearly 50%, unrecognised HF is common among community-dwelling patients with AF. Given the high prior change, natriuretic peptides are diagnostically not helpful, and straightforward echocardiography seems to be the preferred strategy for HF screening in patients with AF.

Topics: Atrial Fibrillation; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Sensitivity and Specificity

Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use of NT-proBNP measurement has been suggested in the context of ARNI therapy because its concentrations are not affected by neprilysin inhibition. As biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the effects of individual patient characteristics, such as renal function and age, on biomarker concentrations should be reassessed.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Drug Combinations; Drug Therapy, Combination; Heart Failure; Humans; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Randomized Controlled Trials as Topic; Tetrazoles; Valsartan

Heart failure (HF) is a rising epidemic due to the ageing population and progress in all areas of medicine. Thus, research efforts are made to ensure a timely diagnosis, to improve prognosis and treatment of the disease and to facilitate risk prediction at the population level. Because of their noninvasive determination with mostly high sensitivity and accuracy, circulating blood biomarkers are becoming increasingly important for daily clinical practice. Natriuretic peptides, especially B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) and cardiac troponins are established blood biomarkers in HF diagnosis and prognosis of HF-related outcomes. Inflammatory molecules as C-reactive protein (CRP) may have added value in anti-inflammatory therapy guidance. Next-generation biomarkers including soluble source of tumorigenicity 2 (sST2), growth differentiation factor-15 (GDF-15), galectin-3 (Gal-3) and diverse microribonucleic acids (miRNAs) may have additional benefit in assessment of cardiac remodeling or differentiation of HF subtypes. Multimarker approaches containing different combinations of established and novel biomarkers might improve HF risk prediction at the population level once they are used on top of clinical variables.

Topics: Biomarkers; C-Reactive Protein; Galectin 3; Growth Differentiation Factor 15; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Troponin

Current guidelines do not support the use of serial natriuretic peptide (NP) monitoring for heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) treatment, despite some studies showing benefit. We conducted an updated meta-analysis to address whether medical therapy in HFpEF or HFrEF should be titrated according to NP levels.. MEDLINE, Scopus and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) comparing NP versus guideline directed titration in HF patients through December 2017. The key outcomes of interest were mortality, HF hospitalizations and all-cause hospitalizations. Risk ratios and 95% confidence intervals were pooled using random effects model. Sub-group analyses were performed for type of NP used, average age and acute or chronic HF.. Eighteen trials including 5116 patients were included. Meta-analysis showed no significant difference between the NP-guided arm versus guideline directed titration in all-cause mortality (RR = 0.91 [0.81, 1.03]; p = 0.13), HF hospitalizations (RR = 0.81 [0.65, 1.01]; p = 0.06), and all cause hospitalizations (RR = 0.93 [0.86, 1.01]; p = 0.09). The results were consistent upon subgroup analysis by biomarker type (NT-proBNP or BNP) and type of heart failure (acute or chronic and HFrEF or HFpEF). Sub-group analysis suggested that NP-guided treatment was associated with decreased all-cause hospitalizations in patients younger than 72 years of age.. The available evidence suggests that NP-guided therapy provides no additional benefit over guideline directed therapy in terms of all-cause mortality and HF-related hospitalizations in acute or chronic HF patients, regardless of their ejection fraction.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome

Acute heart failure (AHF) is a major burden disease, with a complex physiopathology, unsatisfactory diagnosis, treatment and a very poor prognosis. In the last two decades, a number of drugs have progressed from preclinical to early and late clinical development, but only a few of them have been approved and added to a stagnant pharmacological armamentarium. We have reviewed the data published on drugs developed for AHF since early 2000s, trying to recognise factors that have worked for a successful approval or for the stoppage of the program, in an attempt to delineate future trajectories for AHF drug development. Our review has identified limitations at both preclinical and clinical levels. At the preclinical level, the major shortcoming is represented by animal models looking at short-term endpoints which do not recapitulate the complexity of the human disease. At the clinical level, the main weakness is given by the disconnect between short-term endpoints assessed in the early stage of drug development, and medium-long-term endpoints requested in Phase 3 for regulatory approval. This is further amplified by the lack of validation and standardisation of short- and long-term endpoints; absence of predictive biomarkers; conduct of studies on heterogeneous populations; and use of different eligibility criteria, time of assessments, drug schedules and background therapies. Key goals remain a better understanding of AHF and the construction of a successful drug development program. A reasonable way to move forward resides in a strong collaboration between main stakeholders of therapeutic innovation: scientific community, industry and regulatory agencies.

Topics: Acute Disease; Cardiotonic Agents; Drug Approval; Drug Development; Heart Failure; Humans; Natriuretic Peptide, Brain; Simendan

Measuring the level of B-type natriuretic peptide (BNP), as a guide to pharmacotherapy, can increase the survival of patients with heart failure. This study is aimed at systematically reviewing the studies conducted on the cost-effectiveness of BNP-guided care in patients with heart failure. Using the systematic review method, we reviewed the published studies on the cost-effectiveness of BNP-guided care in patients with heart failure during the years 2004 to 2017. The results showed that all studies clearly stated the time horizon of the study and included direct medical costs in their analysis. In addition, most of the studies used the Markov model. The quality-adjusted life years (QALYs) were the main outcome used for measuring the effectiveness. The studies reported various ranges of the incremental cost-effectiveness ratio (ICER); accordingly, the highest ratio was observed in the USA ($32,748) and the lowest ratio was observed in Canada ($6251). Although the results of the studies were different in terms of a number of aspects, such as the viewpoint of the study, the study horizons, and the costs of expenditure items, they reached similar results. Based on the results of the present study, it seems that the use of BNP or N-terminal pro-BNP (NT-pro-BNP) in patients with heart failure may reduce cost compared to the symptom-based clinical care and increase QALY. In this regard, these studies were designed and conducted in high-income countries; thus, the application of these results in low- and middle-income countries will be limited.

Topics: Cardiovascular Agents; Cost-Benefit Analysis; Drug Monitoring; Health Care Costs; Heart Failure; Humans; Natriuretic Peptide, Brain; Quality-Adjusted Life Years

The rising incidence of and the cost associated with heart failure have made it increasingly imperative to accurately diagnose heart failure upon presentation. Correctly identifying heart failure in an Emergency Department is extremely challenging, and according to estimates, is only confirmatory in approximately 40-50% of patients. For an accurate diagnosis of heart failure and the consequent treatment, there needs to be more accurate test relying on biochemical factors as opposed to general symptoms that patients are experiencing. Natriuretic peptides are now utilized in routine tests for heart disease diagnosis in emergency departments as it is relatively low cost, easy to use and is a quick way to exclude heart failure as a reason for dyspnea. In this review, we detail the role and value of individual natriuretic peptides, particularly BNP, NT-proBNP, and MR-proANP, in diagnosing acute heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments

Left ventricular assist device (LVAD) therapy serves as mainstay therapy for bridge to transplantation and destination therapy. Evidence is now mounting on the role of LVAD therapy as bridge to recovery. In the current review, we will summarize the data on biomarkers of myocardial recovery following LVAD implantation.. Myocardial recovery can occur spontaneously, following pharmacological intervention and in the setting of mechanical circulatory support such as LVAD. Several biomarkers such as B-type natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), ST2, etc. have been identified and are being used to guide medical therapy in heart failure (HF) patients. However, recent data raised concern that those biomarkers may not be helpful in managing heart failure patients in general, and as such questioned their use in the advanced heart failure population. At this point, the use of biomarker to identify patients with myocardial recovery during LVAD support has not been established, and LVAD explantation remains a decision driven by echocardiographic and hemodynamics improvement. HF biomarkers in monitoring myocardial and neurohormonal activation response to mechanical unloading and medical therapy could be valuable. However, at this time, there is inadequate evidence to select a single or a set of HF biomarkers to reliably identify patients bridged to recovery for LVAD explantation.

Topics: Biomarkers; Echocardiography; Heart Failure; Heart Ventricles; Heart-Assist Devices; Humans; Natriuretic Peptide, Brain; Recovery of Function; Ventricular Function, Left

Cardiac biomarkers play important roles in routine evaluation of cardiac patients. But while these biomarkers can be extremely valuable, none of them should ever be used by themselves-without adding the clinical context. This paper explores the non-cardiac pathologies that can be seen with the cardiac biomarkers most commonly used.. High-sensitivity troponin assay gained FDA approval for use in the USA, and studies demonstrated its diagnostic utility can be extended to patients with renal impairment. Gender-specific cut points may be utilized for high-sensitivity troponin assays. In the realm of the natriuretic peptides, studies demonstrated states of natriuretic peptide deficiency in obesity and in subjects of African-American race. Regardless, BNP and NT-proBNP both retained prognostic utilities across a variety of comorbid conditions. We are rapidly gaining clinical evidence with use of soluble ST2 and procalcitonin levels in management of cardiac disease states. In order to get the most utility from their measurement, one must be aware of non-cardiac pathologies that may affect the levels of biomarkers as although many of these are actually true values, they may not represent the disease we are trying to delineate. A few take-home points are as follows: 1. A biomarker value should never be used without clinical context 2. Serial sampling of biomarkers is often helpful 3. Panels of biomarkers may be valuable.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Renal Insufficiency; Risk Assessment; Risk Factors; Stroke; Troponin

Acute decompensated heart failure (ADHF) is one of the biggest challenges in the management of chronic heart failure. Despite several advances in medical and device therapy, high readmission and mortality rates continue to be a burden on healthcare systems worldwide. The aim of the current review is to provide an overview on current as well as future approaches in cardiorenal interactions in patients with ADHF.. One of the strongest predictors of adverse outcomes in ADHF is renal dysfunction, referred to as cardiorenal syndromes (CRS) or cardiorenal interactions. Patients with ADHF frequently develop worsening of renal function (WRF) and/or acute kidney injury (AKI). Recent studies brought new information about biomarkers in diagnosing and predicting prognosis of CRS. Among others, dry weight at hospital discharge is considered a surrogate marker of successful treatment in ADHF patients with/without renal dysfunction. The etiology of WRF appears to be an important factor for determining risk related to WRF as well as clinical management. The hypertonic saline used as adjunctive therapy for intravenous loop diuretics and/or induction of aquaresis (e.g., using tolvaptan) may be promising and efficient approaches in the future.

Topics: Acute Disease; Acute Kidney Injury; Biomarkers; Heart Failure; Humans; Kidney Function Tests; Natriuretic Peptide, Brain; Risk Factors

The purpose of this review is to outline the relationship between serum biomarkers of cardiac stress and the pathophysiologic progression of aortic stenosis, to identify studies exploring the utility of biomarkers in the risk stratification and management of patients with aortic stenosis, and to highlight the biomarkers most practical to management of patients with aortic stenosis.. Several biomarkers have been identified that reflect various aspects of the pathogenesis of calcific aortic stenosis, subsequent hemodynamic obstruction leading to myocardial remodeling, oxidative stress and injury, and concomitant systemic inflammation. These markers are associated with adverse outcomes in aortic stenosis and offer incremental value in risk prediction over traditional clinical assessment for aortic stenosis. NTproBNP and troponin are the most rigorously studied serum biomarkers in aortic stenosis, and only NTproBNP is currently reflected in any major guideline on aortic stenosis management. Serum biomarkers show promise in guiding management of aortic stenosis, but still require significant prospective investigation before they can be incorporated in major guidelines.

Topics: Aortic Valve Stenosis; Biomarkers; Cardiac Imaging Techniques; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Severity of Illness Index

We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF).. Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI.. We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53-0.92, patients < 75 years old and HR 1.07, 95% CI 0.84-1.37, patients ≥ 75 years old); ejection fraction (p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71-0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83-2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60).. BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear.. PROSPERO CRD42013005335.

Topics: Cause of Death; Heart Failure; Hospitalization; Humans; Mortality; Natriuretic Peptide, Brain; Quality of Life; Randomized Controlled Trials as Topic

Topics: Biomarkers; Glycosylation; Heart Failure; Humans; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments

How to diagnose heart failure? Abstract. In light of the ongoing demographic development with a continuous increase in people older than 65 years heart failure becomes a growing public health issue. The suspicion of the diagnosis is based on clinical signs and symptoms representing the effects of increased cardiac filling pressure, congestion and hypoperfusion. Natriuretic peptides (BNP and NT-proBNP) are key to corroborate the working diagnosis. In subjects with natriuretic peptide levels above the threshold of exclusion, the diagnosis is confirmed by documenting the underlying functional or structural cardiac alterations using echocardiography.. Zusammenfassung. Herzinsuffizienz hat sich in Anbetracht der demographischen Entwicklung mit einer immer grösser werdenden Bevölkerungsschicht der über 65-Jährigen zu einem wachsenden Problem der öffentlichen Gesundheit entwickelt. Die Verdachtsdiagnose basiert auf typischen Symptomen und klinischen Zeichen, welche den erhöhten intrakardialen Füllungsdruck sowie die Minderperfusion und die daraus resultierende Kongestion widerspiegeln. Die Messung der natriuretischen Peptide (BNP oder NT-proBNP) ist der Schlüssel, um die Arbeitsdiagnose «Herzinsuffizienz» zu erhärten. Die endgültige Bestätigung der Diagnose erfolgt durch die Objektivierung einer funktionellen und / oder strukturellen kardialen Funktionsstörung mittels Echokardiographie.

Topics: Acute Disease; Aged; Biomarkers; Cross-Sectional Studies; Echocardiography; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Population Dynamics; Switzerland

Since 1984, each year, more women than men die of ischemic heart disease (IHD) and heart failure (HF), yet more men are diagnosed. Because biomarker assessment is often the first diagnostic employed in such patients, understanding biomarker differences in men vs. women may improve female morbidity and mortality rates.Some key examples of cardiac biomarker utility based on sex include contemporary use of "unisex" troponin reference intervals under-diagnosing myocardial necrosis in women; greater use of hsCRP in the setting of acute coronary syndrome (ACS) could lead to better stratification in women; and greater use of BNP with sex-specific thresholds in ACS could also lead to more timely risk stratification in women.Accurate diagnosis, appropriate risk management, and monitoring are key in the prevention and treatment of cardiovascular diseases; however, the assessment tools used must also be useful or at least assessed for utility in both sexes. In other words, going forward, we need to evaluate sex-specific reference intervals or cutoffs for laboratory tests used to assess cardiovascular disease to help close the diagnostic gap between men and women.

Topics: Animals; Biomarkers; C-Reactive Protein; Creatine Kinase, MB Form; Female; Heart Failure; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Sex Characteristics; Troponin

Sauna bath has potential as a lifestyle treatment modality for heart failure (HF). It is important to analyze the current evidence to help suggest paths of future study and potential for clinical application.. Sauna bath has a positive effect on HF patients.. PubMed, Cochrane Library, and CINAHL databases were searched to identify randomized and nonrandomized controlled studies to compare effects of sauna bath with no sauna bath. Studies were searched for both infrared sauna bath and Finnish sauna bath. The strength of evidence was rated using a modified GRADE approach. Out of 1444 studies, nine met the inclusion criteria and were included in this review. Seven of these nine studies were included in the meta-analysis. Only studies with infrared sauna bath met the inclusion criteria.. In the meta-analysis, exposure to an infrared sauna bath in 60°C for 15 minutes, followed by a 30-minute rest in warm environment, five times a week for 2 to 4 weeks, was associated with a significant reduction in B-type natriuretic peptide, cardiothoracic ratio, and an improvement in left-ventricular ejection fraction. There was no significant effect on left-ventricular end-diastolic diameter, left atrial diameter, systolic blood pressure, or diastolic blood pressure. The strength of evidence varied from moderate to insufficient.. Infrared sauna bath was associated with short-term improvement in cardiac function. More evidence is needed about long-term effects of sauna bath and the effects of a Finnish sauna on cardiovascular health among patients with HF or other cardiovascular diseases.

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Infrared Rays; Male; Middle Aged; Natriuretic Peptide, Brain; Recovery of Function; Steam Bath; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Several randomized controlled trials (RCTs) have been investigated the benefits of soluble guanylate cyclase (sGC) stimulators in the treatment of heart failure, but a comprehensive evaluation is lacking. We performed a meta-analysis to evaluate the efficacy and safety of oral sGC stimulators (vericiguat and riociguat) in patients with heart failure.. Studies were searched and screened in PubMed, Embase, and Cochrane Library. Eligible RCTs were included that reported mortality, the change of EuroQol Group 5-Dmensional Self-report Questionnaire (EQ-5D) US index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), or serious adverse events (SAEs). Relative risk or weight mean difference (WMD) was estimated using fixed effect model or random effect model. Analysis of sensitivity and publication bias was conducted.. Five trials with a total of 1200 patients were included. sGC stimulators had no impact on the mortality (1.25; 95% confidence interval 0.50-3.11) and significantly improved EQ-5D US index (0.04; 95% confidence interval 0.020-0.05). Furthermore, in comparison with control group, NT-proBNP was statistically decreased in riociguat group (-0.78; 95% confidence interval -1.01 to -0.47), but not in vericiguat group (0.04, 95% confidence interval -0.18 to 0.25). There were not obverse differences in SAEs between sGC stimulators and control groups (0.90; 95% confidence interval 0.72-1.12).. Our meta-analysis suggests that sGC stimulators could improve the quality of life in patients with heart failure with good tolerance and safety, but their long-term benefits need to be observed in the future. sGC stimulators are likely to be promising add-on strategies for the treatment of heart failure.

Topics: Adult; Aged; Enzyme Activators; Female; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pyrazoles; Pyrimidines; Quality of Life; Soluble Guanylyl Cyclase

To assess the efficacy and safety of Nuanxin capsule for patients with heart failure (HF).. A systematic literature search was performed in 6 databases: PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wan-fang Data Information Site, Chinese BioMedical Database (CBM), VIP Chinese Science and Technique Journals Database from the date of its inception up to November 2016. Review Manager 5.2 software was used for assessment of risk of bias, data synthesis and subgroup analysis. Begg and Egger tests were used for assessing symmetries of funnel plot by software Stata 12.0. We conducted the GRADE system to assess the quality of evidence.. 12 trials involving 1418 participants were eligible. Compared with western medicine (WM) alone, Nuanxin capsule plus WM showed statistical significance in total effective rate (RR 1.18, 95% condidence interval [CI] 1.13-1.25). According to subgroup analysis, the 6-months group and the 12-months group have better effect than the 3-month group. As for 6-minute walking distance (6MWT), Nuanxin capsule plus WM compared with WM has significantly increased walking distance (weighted mean difference [WMD] 42.56, 95% CI 34.27-50.85). Nuanxin capsule plus WM has significantly decreased in mortality (RR 0.29, 95% CI 0.18-0.46) and re-admission rate (RR 0.48, 95% CI 0.39-0.60) compared with WM. Nuanxin capsule plus WM was beneficial for B-type natriuretic peptide (-240.47, 95% CI -332.45-148.49). gger's and Begg's test showed that there was no publication bias exist (P = .937). Influence analysis showed that no single study affected the overall result. The GRADE quality of the evidence was very low to Moderate across the different outcomes.. Despite of the apparently positive findings, we cannot draw a sound conclusion that Nuanxin capsule has positive effect in patients with HF, because of the insufficient evidence.

Topics: Adult; Aged; Aged, 80 and over; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome; Walk Test

This review aimed at comprehensively summarizing current available reports regarding the ultrasound markers and biomarkers in predicting fetal Hb Bart's disease and evaluate the potential role of cardiac function assessment in a clinical practice. This review involves various methods in prenatal predicting fetal Hb Bart's disease or alpha-thalassemia major and attempts to provide valuable insights regarding the underlying mechanisms responsible for heart failure in Hb Bart's fetuses. Moreover, this information may be used to predict the cardiac function before the development of hydrops fetalis. Finally, the affected Hb Bart's fetus could be the best model of the study on cardiovascular response to fetal anemia, thus the cardiovascular ultrasound and molecular assessment may be helpful in predicting the prognosis or in making a choice in the management of the fetal anemia condition. In conclusion, ultrasound findings especially cardiomegaly and an increase in peak systolic velocity of the middle cerebral artery (MCA-PSV) are helpful in predicting the future hydrops fetalis and ultrasound assessment of fetal cardiac function is potentially helpful in clinical practice. Finally, this review highlights the pathogenesis of hydropic changes secondary to fetal anemia.

Topics: Abortion, Eugenic; Anemia; Biomarkers; Cardiotocography; Female; Fetal Heart; Fetal Therapies; Heart Failure; Hemoglobins, Abnormal; Humans; Hydrops Fetalis; Middle Cerebral Artery; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Pregnancy; Troponin T; Ultrasonography, Prenatal

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx.

Topics: Biomarkers; Heart Failure; Heart Transplantation; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Right

The natriuretic peptide (NP) system, which includes atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide, has an important role in cardiovascular homeostasis, promoting a number of physiological effects including diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system. Heart failure (HF) is associated with defects in NP processing and synthesis, and there is a strong relationship between NP levels and disease state. NPs are useful biomarkers in HF, and their use in diagnosis and evaluation of prognosis is well established, particularly in patients with HF with reduced ejection fraction (HFrEF). There has also been interest in their use to guide disease management and therapeutic decision making. An understanding of NPs in HF has also resulted in interest in synthetic NPs for the treatment of HF and in treatments that target neprilysin, a protease that degrades NPs. A novel drug, the angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696), which simultaneously inhibits neprilysin and blocks the angiotensin II type I receptor, was shown to have a favorable efficacy and safety profile in patients with HFrEF and has been approved for use in such patients in Europe and the USA. In light of the development of treatments that target neprilysin and of recent data in relation to synthetic NPs, it is timely to review the current understanding of the role of NPs in HF and their use in diagnosis, evaluating prognosis and guiding treatment, as well as their place in HF therapy.

Topics: Disease Management; Heart Failure; Homeostasis; Humans; Natriuretic Peptide, Brain; Renin-Angiotensin System

Testing for natriuretic peptides (BNP, NT-proBNP or MR-proANP) is recommended by the European Society of Cardiology (ESC) since 2005 for the exclusion diagnosis of acute and chronic heart failure because of very high predictive values. Natriuretic peptides are produced by the heart in response to high transmural pressure and/or myocardial ischemia. These peptides circulate in blood of both healthy subjects and heart failure patients. Mass spectrometry methods allowed identifying a collection of circulating and degraded forms of BNP, NT-proBNP and proBNP. Glycosylated forms of NT-proBNP and proBNP have also been identified. Current immunoassays are lacking analytical specificity due to high cross-reactivities between circulating forms. Moreover, glycosylation has been found to interfere with the capacity of antibodies to bind correctly to analytes. These elements have been taken into account to propose strategies for the development of new standardized and improved immunoassays. More recently, the better understanding of the degradation pathways of natriuretic peptides allowed the raise of new therapeutic approaches for heart failure patients. All these elements are detailed in this review.

Topics: Animals; Biomarkers; Cross Reactions; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Protein Isoforms; Proteolysis; Sensitivity and Specificity

LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Antihypertensive Agents; Atrial Natriuretic Factor; Biphenyl Compounds; Clinical Trials as Topic; Cough; Cyclic GMP; Diuresis; Drug Combinations; Heart Failure; Heart Ventricles; Humans; Hypertension; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Valsartan; Vasodilation

Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Renal Insufficiency; Renal Replacement Therapy

The use of biomarkers in heart failure (HF) is a rapidly changing field. The purpose of this review is to assess the current evidence of the use of biomarkers for risk stratification in patients with HF with preserved ejection fraction (HFpEF).. Despite differences in pathophysiology between HF with reduced ejection fraction and HFpEF, traditional HF biomarkers such as brain natriuretic peptide and troponin retain prognostic value in most HFpEF-specific populations. Biomarkers of key pathophysiologic components of HFpEF, such as myocardial fibrosis, remodeling, and systemic inflammation are also valuable prognostic markers. Further investigation into HF biomarkers may identify significant therapeutic targets for the treatment of HFpEF.

Topics: Biomarkers; Global Health; Heart Failure; Humans; Morbidity; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Stroke Volume; Survival Rate; Troponin

The aim of this study was to explore the prognostic value of copeptin for predicting all-cause mortality in heart failure (HF).. PubMed, Embase and Cochrane databases were systematically searched to identify if a 2×2 contingency table could be constructed based on both the copeptin level and the all-cause mortality in patients diagnosed with HF. The characteristics of test performance were summarized using forest plots and summary receiver operating characteristic curves (SROC). Q-test and I. Ten prospective cohort studies comprising 4473 patients were eligible in this meta-analysis. An elevated copeptin level was associated with an increased risk of all-cause mortality in HF patients (Relative risk (RR) was 2.64 (95% CI, 2.09-3.32)). The pooled sensitivity (SEN) and specificity (SPE) of copeptin were 0.57 (95% CI, 0.50-0.63) and 0.74 (95% CI, 0.69-0.79), respectively. The positive likelihood ratio was 2.2 (95% CI, 1.90-2.60) and the negative likelihood ratio was 0.58 (95% CI, 0.52-0.66). Furthermore, the summary Diagnostic Odds Ratio (DOR) was 4.00 (95% CI, 3.00-5.00) and the AUC was 0.70 (95% CI, 0.66-0.74) similar to the AUC of NT-proBNP 0.71 (95% CI, 0.67-0.75).. Elevated levels of copeptin are associated with all-cause mortality in HF patients. The predictive value of copeptin is comparable with NT-proBNP for all-cause mortality in HF patients. Further studies are warranted to explore the prognostic value of copeptin in conjunction with other biomarkers and to determine an optimal cut-off level.

Topics: Biomarkers; Female; Gene Expression; Glycopeptides; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prognosis; Prospective Studies; Risk; ROC Curve; Survival Analysis

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

Heart failure (HF) continues to be a public health burden despite advances in therapy, and the natriuretic peptide (NP) system is clearly of critical importance in this setting, spawning valuable diagnostic and prognostic testing, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), as well as current and future therapeutics, including recombinant natriuretic peptides (e.g., carperitide, nesiritide) and recently sacubitril, which inhibits the key clearance mechanism for NPs. This article intends to summarize the existing evidence for the role of NP system genetic variation on cardiovascular phenotypes relevant to HF with particular focus on the potential impact on pharmacologic therapies.. Several genes in NP system have been interrogated, in many cases genetic variation impacting protein quantity and function or related disease states. Recent data supports genetic variants potentially impacting pharmacokinetics or dynamics of medications targeting the pathway. Growing evidence indicates the importance of genetic variation to the functioning of the NP system and its pharmacologic manipulation.

Topics: Biomarkers; Genotype; Heart Failure; Humans; Natriuretic Peptide, Brain; Polymorphism, Genetic; Prognosis

Heart failure with left ventricular dysfunction occurring during pregnancy or during the post-partum period in patients without history of cardiovascular disease defines peripartum cardiomyopathy (PPCM). PPCM carries a high morbidity and mortality rate as well as the possibility of recovery ad integrum. Its incidence shows ethnic variations, with a greater prevalence of the disease among women with African descent. Pathogenesis of PPCM remains poorly understood. Both "oxidative stress-prolactin axis" and "anti-angiogenic-signaling excess" hypotheses are currently being investigated. Novel diagnostic strategies and biomarkers are currently being evaluated. Besides conventional treatment of heart failure, targeted therapies such as pharmacological prolactin blockade are under evaluation. The aim of this short review is to highlight current management as targeted therapy has far been disappointing.

Topics: Bromocriptine; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hormone Antagonists; Humans; Incidence; Natriuretic Peptide, Brain; Oxidative Stress; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prolactin; Radiography, Thoracic; 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

Acute decompensated heart failure (ADHF) requiring hospitalization is associated with high postdischarge mortality and readmission rates.. To examine the association between achieving predischarge natriuretic peptide (NP) thresholds and mortality and readmission rates in adults hospitalized for ADHF.. Multiple databases from 1947 to October 2016 (English-language studies only).. Trials and observational studies that compared mortality and readmission outcomes between patients with ADHF achieving a specific predischarge NP goal and those not achieving the goal.. Two investigators independently extracted study characteristics and assessed study risk of bias. One author graded the overall strength of evidence, with review by a second author.. One randomized trial, 3 quasi-experimental studies, and 40 observational studies were identified. The most commonly used thresholds were a brain-type NP (BNP) level of 250 pg/mL or less or an amino-terminal pro-brain-type NP (NT-proBNP) decrease of at least 30%. Achievement of absolute BNP thresholds reduced postdischarge all-cause mortality (7 of 8 studies) and the composite outcome of mortality and readmission (12 of 14 studies). Achievement of percentage-change BNP thresholds reduced the composite outcome (5 of 6 studies), and achievement of percentage-change NT-proBNP thresholds reduced all-cause and cardiovascular mortality (2 of 4 studies) and the composite outcome (9 of 9 studies). All findings were low-strength. The randomized trial, assessed as having high risk of bias, suggested that a predischarge decrease in NT-proBNP level was associated with lower risk for the composite outcome. Two quasi-experimental studies and 5 observational studies had low risk of bias. Low-risk-of-bias studies had outcome estimates similar in magnitude and direction to estimates from high-risk-of-bias studies.. Most studies failed to adjust for critical confounders and had inadequate definition or assessment of exposures and outcomes.. Low-strength evidence suggests an association between achieving NP predischarge thresholds and reduced ADHF mortality and readmission.. None.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Peptide Fragments; Risk Factors

Heart failure with reduced ejection fraction (HFrEF) is a progressive disorder whereby cardiac structure and function continue to deteriorate, often despite the absence of clinically apparent signs and symptoms of a worsening disease state. This silent yet progressive nature of HFrEF can contribute to the increased risk of death-even in patients who are 'clinically stable', or who are asymptomatic or only mildly symptomatic-because it often goes undetected and/or undertreated. Current therapies are aimed at improving clinical symptoms, and several agents more directly target the underlying causes of disease; however, new therapies are needed that can more fully address factors responsible for underlying progressive cardiac dysfunction. In this review, mechanisms that drive HFrEF, including ongoing cardiomyocyte loss, mitochondrial abnormalities, impaired calcium cycling, elevated LV wall stress, reactive interstitial fibrosis, and cardiomyocyte hypertrophy, are discussed. Additionally, limitations of current HF therapies are reviewed, with a focus on how these therapies are designed to counteract the deleterious effects of compensatory neurohumoral activation but do not fully prevent disease progression. Finally, new investigational therapies that may improve the underlying molecular, cellular, and structural abnormalities associated with HF progression are reviewed.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Apoptosis; Atrial Natriuretic Factor; Biphenyl Compounds; Calcium; Disease Progression; Diuretics; Drug Combinations; Fibrosis; Heart Failure; Humans; Mitochondria, Heart; Myocardium; Myocytes, Cardiac; Natriuretic Agents; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Stress, Mechanical; Stroke Volume; Tetrazoles; Valsartan; Ventricular Dysfunction, Left

Patients with chronic obstructive pulmonary disease (COPD) have increased cardiovascular risk. Natriuretic peptides (NP) in other populations are useful in identifying cardiovascular disease, stratifying risk, and guiding therapy.. We performed a systematic literature review to examine NP in COPD, utilising Medline, EMBASE, and the Cochrane Library.. Fifty one studies were identified. NP levels were lower in stable compared to exacerbation of COPD, and significantly increased with concomitant left ventricular systolic dysfunction or cor pulmonale. Elevation occurred in 16 to 60% of exacerbations and persisted in approximately one half of patients at discharge. Cardiovascular comorbidities were associated with increased levels. Levels consistently correlated with pulmonary artery pressure and left ventricular ejection fraction, but not pulmonary function or oxygen saturation. NP demonstrated high negative predictive values (0.80 to 0.98) to exclude left ventricular dysfunction in both stable and exacerbation of COPD, but relatively low positive predictive values. NP elevation predicted early adverse outcomes, but the association with long term mortality was inconsistent.. NP reflect diverse aspects of the cardiopulmonary continuum which limits utility when applied in isolation. Strategies integrating NP with additional variables, biomarkers and imaging require further investigation.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Risk Factors; Ventricular Dysfunction, Left

Biomarkers are increaingly being used in the management of heart failure not only for the purpose of screening, diagnosis, and risk stratification, but also as a guide to evaluate the response to treatment in the individual patient and as an entry criterion and/or a surrogate marker of efficacy in clinical trials testing novel drugs. In this chapter, we review the role of established biomarkers for heart failure management, according to the main classification of HF phenotypes, based on the measurement of left ventricular ejection fraction, including heart failure with reduced (<40%), preserved (≥50%), and, as recently proposed, mid-range (40-49%) ejection fraction.

Topics: Adrenomedullin; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; beta-N-Acetyl-Galactosaminidase; Biomarkers; C-Reactive Protein; Cardio-Renal Syndrome; Catecholamines; Chromogranin A; Creatinine; Galectin 3; Glycopeptides; Growth Differentiation Factor 15; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-1; Interleukin-1 Receptor-Like 1 Protein; Interleukin-18; Interleukin-6; Lipocalin-2; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Renin; Renin-Angiotensin System; Stroke Volume; Troponin; Troponin T; Tumor Necrosis Factor-alpha

This meta-analysis aimed to update and evaluate evidence from randomized controlled trials of tai chi for patients with chronic heart failure.. Both English and Chinese databases were searched from their inception to June 2, 2016 (PubMed, EMBASE, Cochrane Central Register of Controlled Trials for English publications and China Knowledge Resource Integrated, Wanfang, and Weipu databases for Chinese publication). Titles, abstracts, and full-text articles were screened against study inclusion criteria: randomized controlled trials studying tai chi intervention for patients with chronic heart failure. The meta-analysis was conducted with Revman 5.3 or STATA 12.. Thirteen randomized controlled trials were included. Tai chi induced significant improvement in 6-min walking distance (51.01 m; 30.49-71.53; P < 0.00). Moreover, tai chi was beneficial for quality of life (-10.37 points; -14.43 to -6.32; P = 0.00), left ventricular ejection fraction (7.72%; 3.58-11.89; P = 0.003), and B-type natriuretic peptide (-1.01; -1.82 to -0.19; P = 0.02).. Despite heterogeneity and risk of bias, this meta-analysis further confirms that tai chi may be an effective cardiac rehabilitation method for patients with chronic heart failure. Larger, well-designed randomized controlled trials are needed to exclude the risk of bias.

Topics: Exercise Tolerance; Heart Failure; Natriuretic Peptide, Brain; Quality of Life; Randomized Controlled Trials as Topic; Stroke Volume; Tai Ji; Walking

B-type natriuretic peptides are markers of myocardial wall stress. BNP or NT-proBNP are used for the differential diagnosis of acute dyspnoe where normal serum concentrations make a cardiac cause unlikely. New data show their importance for risk prediction in different stages of heart failure and in primary prevention. Natriuretic peptide guided therapy improves titration of heart failure medications. Compared to BNP, NT-proBNP is better suited during therapy with the new angiotensin-rezeptor-neprilysin-inhibitor Sacubitril/Valsartan. This review article summarizes current data on the importance of B-type natriuretic peptides for the interface of ambulatory and hospital care and presents recommendations for their practical use in patient care.

Topics: Biomarkers; Dyspnea; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity

Natriuretic peptides (NPs) have demonstrated their value to support clinical diagnosis of heart failure (HF); furthermore they are also studied for their prognostic role using them to guide appropriate management strategies. The present review gathers available evidence on prognostic role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF).. We searched Medline for English-language studies with the sequent key-words: "acute heart failure/acute decompensated heart failure", "NT-proBNP/N-terminal pro-B type natriuretic peptide" and "prognosis/mortality/readmission".. Almost 30 studies were included. NT-proBNP plasma levels at admission are strongly associated with all-cause short-term mortality (2-3 months), mid-term (6-11 months) or long- term mortality (more than one year) of follow-up. Regarding the prognostic power on cardiac death fewer data are available with uncertain results. NT-proBNP at discharge demonstrated its prognostic role for all-cause mortality at mid and long-term follow-up. The relation between NT-proBNP at discharge and cardiovascular mortality or composite end-point is under investigation. A decrease in NT-proBNP values during hospitalization provided prognostic prospects mainly for cardiovascular mortality and HF readmission. A 30% variation in NT-proBNP levels during in-hospital stay seemed to be an optimal cut-off for prognostic role.. SNT-proBNP plasma levels proved to have a strong correlation with all-cause mortality, cardiovascular mortality, morbidity and composite outcomes in patients discharged after an ADHF. A better definition of the correct time of serial measurements and the cut-off values might be the challenge for the future investigations.

Topics: Acute Disease; Biomarkers; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Predictive Value of Tests; Prognosis; Time Factors

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

To date, heart failure (HF) prognosis is still difficult: symptoms and signs are often non-specific, and poor sensitive indicators for HF severity. Brain natriuretic peptide (BNP) is now included in the current guidelines for HF diagnosis, management and risk assessment because of its high specificity and sensibility. BNP became a first-line exam in HF patients' evaluation at hospital admission together with clinical and chest X-ray. In discharged patients, the prognostic role of BNP is associated with decongestion and its significant reduction compared to admission level appears one of the best outcome predictors. In fact BNP measurement could identify patients with increased risk of adverse events and left ventricular remodeling. Although a single BNP value assay and the absolute value during hospitalization is related to the prognosis, especially at discharge. On the other hand, hormone levels could be influenced by several factors (i.e., renal dysfunction, anemia, age, liver insufficiency, Body Mass Index) independently from systemic and pulmonary congestion. Therefore, a new approach which considers a multimodality strategy including BNP assay among the traditional clinical examination and imaging studies should be routinely encouraged to better define cardiac dysfunction's etiology and severity, as well as to recognize patients at risk of adverse outcome.

Topics: Biomarkers; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Patient Discharge; Predictive Value of Tests; Prognosis; Risk Assessment; Sensitivity and Specificity

Current evidence suggests that nesiritide may have effects on renal function and decrease the incidence of mortality. However, a clear superiority using nesiritide in terms of renal toxicity and mortality in patients with heart failure was not consistently proven by previous studies. We performed a meta-analysis of all randomised trials to obtain the best estimates of efficacy and safety of nesiritide for the initial treatment of decompensated heart failure.. We performed a meta-analysis of randomised trials of nesiritide in patients with decompensated heart failure (n=38,064 patients, in 22 trials). Two reviewers independently extracted data. Data on efficacy and safety outcomes were collected. We calculated pooled relatives risk (RRs), weighted mean difference and associated 95% CIs.. Compared with placebo, dobutamine and nitroglycerin, nesiritide indicated no increasing risk of total mortality. Compared with the combined control therapy, nesiritide was associated with non-significant differences in short-term mortality (RR 1.24; 95% CI 0.85 to 1.80; p=0.27), mid-term mortality (RR 0.86; 95% CI 0.60 to 1.24; p=0.42) and long-term mortality (RR 0.94; 95% CI 0.75 to 1.18; p=0.61). Nesiritide therapy increased the risk of hypotension (p<0.00 001) and bradycardia (p=0.02) when compared with control therapy. Compared with dobutamine or placebo therapy, no differences in serum creatinine, blood urea nitrogen and creatinine clearance, and no risk of the need for dialysis was observed in nesiritide therapy.. Our findings indicated that, in patients with heart failure, nesiritide was not associated with the risk of mortality. However, it increased the risk of cardiovascular adverse events. The change of serum creatinine and creatinine clearance had no significant difference, and no risk of the need for dialysis was observed after low-dose nesiritide treatment.

Topics: Heart Failure; Humans; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Nitroglycerin; Randomized Controlled Trials as Topic; Treatment Outcome; Vasodilator Agents

Natriuretic peptides, high-sensitivity cardiac troponins, and suppression of tumorigenicity 2 are novel biomarkers that reflect the intricate pathophysiology of heart failure and can thus be used for the diagnosis, management, and prognosis of heart failure.. This review article describes the significance of B-type natriuretic peptide (BNP), N-terminal prohormone of BNP, ST2, and cardiac troponins. We outline their new roles in guiding the management of heart failure as well as strong prognostic indicators for adverse cardiovascular outcomes.. By recognizing the diagnostic and prognostic significance of these biomarkers, clinicians can utilize these biomarkers to more accurately evaluate and risk stratify patients. These markers can also be used to help guide the medical management of heart failure. The best approach for an accurate diagnosis, management, and prognosis of heart failure will likely involve a multimarker panel of biomarkers, which may include high-sensitivity troponins, BNP, N-terminal prohormone of BNP, and ST2.

Topics: Biomarkers; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Receptors, Cell Surface; Reproducibility of Results; Troponin T

Biomarkers have become an integral part of practicing medicine, especially in heart failure. The natriuretic peptides are commonly used in the evaluation of heart failure, but their role extends beyond diagnosis and includes risk stratification and management of heart failure patients. Newer biomarkers have arrived and are becoming part of routine care of heart failure patients. Both ST2 and high-sensitivity troponin have significant prognostic value for mortality, but also may assist in the titration of medical therapy. Procalcitonin can help guide appropriate antibiotic use in patients with heart failure. The ability to appropriately use and interpret these biomarkers is imperative to the care of heart failure patients, especially as these newer biomarkers become widely used.

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Calcitonin; Comorbidity; Diagnosis, Differential; Diuretics; Dyspnea; Female; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Patient Discharge; Pneumonia, Bacterial; Prognosis; Severity of Illness Index; Spironolactone; Survival Analysis; Troponin

To discuss the characteristics of Chinese medicine (CM) syndrome factors and distribution of congestive heart failure (CHF), and provide a basis for the diagnosis criteria of essential syndromes.. Based on databases of China National Knowledge Infrastructure (CNKI, 1980-2012) and Chinese Journal of Chongqing VIP Database (1989-2012), the eligible studies in CHF and extracted factors associated with compound syndromes were analyzed. All the syndromes were classified into deficiency, excess, and deficiency-excess in complexity syndrome were classified. Compound syndromes were separated into syndrome factors including single, double, three or four factors, along with the frequency of occurrence. The relation of CHF syndromes with age, gender, primary disease, brain natriuretic peptide (BNP) and cardiac functional grade was studied in 1,451 CHF cases (between December 2010 and September 2012), and the clinical distribution of common CHF syndromes was summarized.. The literature study involved 6,799 CHF cases in 66 literatures after screening. Of the different factors affecting CHF, qi deficiency was the most important one. In deficiency syndrome, Xin (Heart)-qi-deficiency was the most common single factor, and deficiency of both qi and yin was the most common double factor. The retrospective analysis involved 1,451 CHF cases (431 cases with test results of BNP). The xin blood stasis and obstruction and deficiency of both qi and yin syndrome were mostly seen in female patients, and phlegm-blocking-Xin-vessel and qi-deficiency-blood-stasis syndrome mostly in males. Xin-qi-deficiency and qi-deficiency-blood-stasis syndrome were mostly seen in patients aged 50-60 years. Patients aged over 60 years likely manifest deficiency of both qi and yin and Xin blood stasis and obstruction syndrome. The severity of syndrome is aggravated with increased BNP and cardiac functional grade.. The essential syndromes of CHF include qi-deficiency-blood-stasis and deficiency of both qi and yin. The clinical distribution is linked to patients' age and gender. BNP and cardiac functional grade is closely related to CHF syndromes, which may indicate the severity of CM syndromes of CHF.

Topics: Aged; Aged, 80 and over; Heart Failure; Humans; Medicine, Chinese Traditional; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Syndrome

Acute heart failure (AHF) is one of the most common diagnoses assigned to emergency department (ED) patients who are hospitalized. Despite its high prevalence in the emergency setting, the diagnosis of AHF in ED patients with undifferentiated dyspnea can be challenging.. The primary objective of this study was to perform a systematic review and meta-analysis of the operating characteristics of diagnostic elements available to the emergency physician for diagnosing AHF. Secondary objectives were to develop a test-treatment threshold model and to calculate interval likelihood ratios (LRs) for natriuretic peptides (NPs) by pooling patient-level results.. PubMed, EMBASE, and selected bibliographies were searched from January 1965 to March 2015 using MeSH terms to address the ability of the following index tests to predict AHF as a cause of dyspnea in adult patients in the ED: history and physical examination, electrocardiogram, chest radiograph (CXR), B-type natriuretic peptide (BNP), N-terminal proB-type natriuretic peptide (NT-proBNP), lung ultrasound (US), bedside echocardiography, and bioimpedance. A diagnosis of AHF based on clinical data combined with objective test results served as the criterion standard diagnosis. Data were analyzed using Meta-DiSc software. Authors of all NP studies were contacted to obtain patient-level data. The Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) for systematic reviews was utilized to evaluate the quality and applicability of the studies included.. Based on the included studies, the prevalence of AHF ranged from 29% to 79%. Index tests with pooled positive LRs ≥ 4 were the auscultation of S3 on physical examination (4.0, 95% confidence interval [CI] = 2.7 to 5.9), pulmonary edema on both CXR (4.8, 95% CI = 3.6 to 6.4) and lung US (7.4, 95% CI = 4.2 to 12.8), and reduced ejection fraction observed on bedside echocardiogram (4.1, 95% CI = 2.4 to 7.2). Tests with low negative LRs were BNP < 100 pg/mL (0.11, 95% CI = 0.07 to 0.16), NT-proBNP < 300 pg/mL (0.09, 95% CI = 0.03 to 0.34), and B-line pattern on lung US LR (0.16, 95% CI = 0.05 to 0.51). Interval LRs of BNP concentrations at the low end of "positive" results as defined by a cutoff of 100 pg/mL were substantially lower (100 to 200 pg/mL; 0.29, 95% CI = 0.23 to 0.38) than those associated with higher BNP concentrations (1000 to 1500 pg/mL; 7.12, 95% CI = 4.53 to 11.18). The interval LR of NT-proBNP concentrations even at very high values (30,000 to 200,000 pg/mL) was 3.30 (95% CI = 2.05 to 5.31).. Bedside lung US and echocardiography appear to the most useful tests for affirming the presence of AHF while NPs are valuable in excluding the diagnosis.

Topics: Acute Disease; Diagnosis, Differential; Dyspnea; Echocardiography; Electrocardiography; Emergency Service, Hospital; Heart Failure; Humans; Lung; Natriuretic Peptide, Brain; Peptide Fragments; Physical Examination; Radiography, Thoracic

Heart failure (HF) is a complex clinical condition. The newer guidelines have phased out the designations of systolic and diastolic HF and replaced them with the more physiologically applicable classifications of HF with reduced or preserved ejection fraction (EF). Although the numbers of new patients within these two groups are similar, patient characteristics and risk factors often differ. There also are differences in the incidence of HF among racial and ethnic groups, with blacks having the highest incidence. Although survival has improved over time among patients with reduced EF, no significant change in survival has been observed among those with preserved EF. Many models have been proposed to explain the underlying pathophysiology of HF, including the hemodynamic, neurohumoral, and cardiorenal models. The evaluation of a patient with signs and symptoms of and risk factors for HF includes a detailed history and physical examination, laboratory tests, chest x-ray, electrocardiography, and echocardiography. Serum natriuretic peptide levels are already in use, and other novel biomarkers reflecting the different pathophysiologic pathways are being investigated. The Seattle Heart Failure Model is a tool available for clinicians to use in estimating patient mortality risk.

Topics: Adrenomedullin; Biomarkers; Echocardiography; Electrocardiography; Galectin 3; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Physical Examination; Radiography, Thoracic; Risk Factors; Stroke Volume; Troponin I; Troponin T

Since its discovery in 1988, B-type natriuretic peptide (BNP) has been recognized as a powerful cardiovascular biomarker for a number of disease states, specifically heart failure. Concurrent with such a discovery, much effort has been allocated to the precise monitoring of physiological BNP levels. Thus, it can be used to guide the therapy of heart failure and determine the patient's stage of disease. Thus, we discuss in this article BNP as a potent biomarker. Subsequently, we will review the progress of biosensing devices as they could be applied to monitor BNP levels as assays, benchtop biosensors and implantable biosensors. The analytical characteristics of commercially available BNP assays are presented. Still emerging as a field, we define four obstacles that present opportunity for the future development of implantable biosensor: foreign body response, sensor renewability, sensitivity and selectivity.

Topics: Biomarkers; Biosensing Techniques; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain; Peptide Fragments

Several biomarkers have been tested for screening, diagnosis and prognosis purposes, as well as to guide treatment in heart failure, but only the assay of circulating B-type natriuretic peptides has widely recognized applications for clinical decision-making. Natriuretic peptides are sensitive in detecting the clinically overt or subclinical myocardial damage, but their plasma levels are increased following every generic insult to the cardiovascular system. Novel biomarkers are required to identify specific pathways of disease progression, such as diverse neurohormonal axes activation, inflammation and fibrogenesis, and to act as a tool for therapeutic tailoring. In this view, Gal-3 and ST-2 assays seem very promising, given their involvement in mechanisms of cardiac fibrosis and their prognostic value.

Topics: Biomarkers; Disease Progression; Galectin 3; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Prognosis

Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

Topics: Biomarkers; Clinical Trials as Topic; Decision Making; Disease Management; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Risk Factors

B-type natriuretic peptide (BNP) is primarily synthesized by the ventricles of the heart as a 108-amino acid polypeptide precursor (i.e., proBNP), which is then cleaved into a 76-amino acid biologically inert N-terminal fragment (NT-proBNP) and a biologically active 32-amino acid peptide (BNP). The generation of BNP is considerably enhanced in response to high ventricular filling pressures, so that the measurement of either the active hormone or NT-proBNP has become a mainstay in patients with congestive heart failure. Recent evidence was brought that the enzyme neprilysin efficiently degrades circulating BNP in vivo, whereas proBNP and NT-proBNP are virtually resistant to enzymatic cleavage. Increasing emphasis is currently placed on the fact that that measuring BNP in patients taking the novel and promising neprilysin inhibitors such as LCZ696 may not reliably reflect cardiac dysfunction. Since laboratory monitoring in patients with heart failure should be aimed to define the role of BNP in modulating fluid hemostasis and cardiac remodeling, but natriuretic peptides should also serve as reliable biomarkers of cardiac function and treatment response in these patients, the assessment of neither BNP nor NT-proBNP alone provides a comprehensive biological and clinical picture. Therefore, it seems reasonable to suggest both BNP and the neprilysin-resistant peptide NT-proBNP should be concomitantly assessed in patients with heart failure who take neprilysin inhibitors, so allowing to concomitantly monitor the progression of heart failure and to assess the actual cardiorenal potency of circulating BNP.

Topics: Aminobutyrates; Animals; Biphenyl Compounds; Drug Combinations; Drug Monitoring; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Tetrazoles; Valsartan

Several studies indicated that B-type natriuretic peptide (BNP) assay is able to detect patients even in the early phases of heart failure (HF), when the myocardial remodeling process may be still reversible. BNP assay may assist the physician to initiate appropriate and prompt pharmacological treatments. However, clinical relevance and result interpretation of BNP assay for the guide of therapy or in particular clinical conditions, such as renal failure or treatment with inhibitors of enzymes degrading BNP in HF patients, are still debated. The aim of this article is to discuss some still controversial issues concerning the clinical use of measurement of cardiac natriuretic peptides, and also to provide a general overview and some perspectives related to pathophysiological mechanisms of HF.

Topics: Atrial Natriuretic Factor; Biomarkers; Forecasting; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Renal Insufficiency

Heart failure management is complex and constantly evolving. The American College of Cardiology and the American Heart Association (ACC/AHA) last issued evidence-based guidelines in 2013, and since then, new drugs and devices have been developed. This review presents an evidence-based approach to current heart failure management.

Topics: Adrenergic beta-Antagonists; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiac Resynchronization Therapy Devices; Defibrillators, Implantable; Digoxin; Diuretics; Drug Combinations; Evidence-Based Medicine; Exercise; Heart Failure; Heart-Assist Devices; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Systole; Tetrazoles; Valsartan

Brain natriuretic peptide (BNP), also known as a B-type natriuretic peptide, is one of the important biomarkers with a proven role in the diagnosis of congestive heart failure (CHF). Researchers from the different clinical field have researched into the performance features of BNP testing in the acute care set-up to assist and improve in diagnosing CHF and in predicting future morbidity and mortality rates. The potency of BNP has also been researched into in cases like myocardial ischemia and infarction, cor pulmonale, and acute pulmonary embolism (PE). Based on their vaso-dilatory and diuretic properties and ability to inhibit renin-angiotensin-aldosterone system, natriuretic peptides are able to provide an efficient technique and mechanism of action in the pathophysiologic framework for CHF treatment and management. Recent clinical studies reported that ularitide, a synthetic form of urodilatin, secreted by kidney may be effective in managing and treatment of decompensated heart failure. It has also been reported that Nesiritide, a recombinant natriuretic peptide has been proven to improve dyspnea and hemodynamic parameters in heart failure patients. This review provides an update on natriuretic peptides and their therapeutic potential in CHF treatment.

Topics: Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Biomarkers; Heart Failure; Hemodynamics; Humans; Kidney; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System

Baroreflex activation therapy (BAT) produces a central inhibition of cardiac sympathetic outflow and, concomitantly, an increased cardiac vagal activity via a physiological reflex pathway. In a pilot study in 11 patients with NYHA class III heart failure (HF), BAT produced a persistent significant reduction of muscle sympathetic nerve activity over a 21-month follow-up and a dramatic decrease in the number and length of hospitalizations. In a multinational, prospective, randomized, parallel-controlled, clinical trial in 146 NYHA functional class III HF, BAT produced a significant N-terminal pro-brain natriuretic peptide reduction (p = 0.02). This was associated with a trend toward few in hospital days for HF. BAT might become a powerful tool to manipulate autonomic alterations of HF at their origin and thus profoundly affect advanced HF patient prognosis.

Topics: Autonomic Nervous System; Baroreflex; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prospective Studies; Randomized Controlled Trials as Topic; Sympathetic Nervous System

This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF).. The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies.. Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05).. The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF.

Topics: Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Randomized Controlled Trials as Topic; Recombinant Proteins

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

Many new clinical trials about the effect of omega-3 polyunsaturated fatty acids (PUFAs) in heart failure (HF) patients have shown inconsistent results. Therefore, a meta-analysis of randomised controlled trials (RCTs) was performed to determine the benefits of omega-3 PUFAs in HF patients. Articles were obtained from PubMed, EMBASE, and the Cochrane Library. RCTs comparing omega-3 PUFAs with placebo for HF were included. Two reviewers independently extracted the data from the selected publications. The

Topics: Cardiomyopathy, Dilated; Databases, Factual; Dietary Supplements; Fatty Acids, Omega-3; Heart Failure; Humans; Natriuretic Peptide, Brain; Norepinephrine; Randomized Controlled Trials as Topic; Risk Assessment; Ventricular Function, Left

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high rates of morbidity and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, clinicians are often confronted with these patients and yet have little guidance on how to effectively diagnose and manage them. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolic dysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and consider invasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosis of HFpEF; (4) elevated pulmonary artery systolic pressure on echocardiography in the presence of a normal ejection fraction should prompt consideration of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patients with unexplained dyspnea or exercise tolerance; (6) all patients with HFpEF should be systematically evaluated for the presence of coronary artery disease; (7) use targeted treatment for HFpEF patients based on their phenotypic classification; (8) treat HFpEF patients now by treating their comorbidities; (9) understand the importance of heart rate in HFpEF- lower is not always better; and (10) do not forget to consider rare diseases ("zebras") as causes for HFpEF when evaluating and treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients with HFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies.

Topics: Animals; Echocardiography; Heart Failure; Heart Rate; Hemodynamics; Humans; Natriuretic Peptide, Brain

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

NP is a biomarker that has been used in the diagnosis, management, and prognostication of a number of cardiovascular disorders in the pediatric population. The physiological role of this hormone is to allow the myocardium to adapt to stress or strain imposed by a volume and/or pressure load.. The aim of this study was to determine the utility of preoperative and postoperative NP to predict outcome in pediatric patients undergoing cardiac surgery for structural congenital heart disease.. We conducted a systematic review by searching three electronic databases using the search terms 'paediatric' or 'pediatric' and 'B-type natriuretic peptide'. Twenty peer-reviewed papers were included in the study.. Preoperative NP levels were associated with the severity of cardiac failure in several studies. Preoperative NPs also correlated with early postoperative outcome measures such as duration of cardiopulmonary bypass, duration of mechanical ventilation, presence of low cardiac output syndrome, length of stay in the intensive care unit and in one study, death. Early (within 24 h) postoperative NPs showed a stronger correlation than preoperative NPs to early postoperative adverse events.. NPs provide a simple, noninvasive and complementary tool to echocardiography that can be used to assist clinicians in the assessment and management of pediatric patients with congenital heart disease in the perioperative period.

Topics: Biomarkers; Cardiac Output, Low; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Heart Defects, Congenital; Heart Failure; Humans; Length of Stay; Natriuretic Peptide, Brain; Pediatrics; Perioperative Period; Postoperative Period; Respiration, Artificial; Severity of Illness Index; Time Factors

Addison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive. Following this, if a patient with Addison's disease remains hypertensive, the fludrocortisone dose should be reviewed and reduced if there are clinical and/or biochemical signs of mineralocorticoid excess. In the absence of such signs, where the renin is towards the upper end of the normal range or elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose should remain unchanged. Dihydropyridine calcium channel blockers are clinically useful as second line agents, but diuretics should be avoided. In the setting of heart failure, there is an increase in total body sodium and water; therefore, it is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop diuretics may be used, but not aldosterone antagonists such as spironolactone or eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII receptor antagonists, are appropriate. Measurements of renin are no longer helpful in heart failure to determine the volume status but plasma levels of brain natriuretic peptide (BNP/proBNP) may help guide therapy.

Topics: Addison Disease; Angiotensin-Converting Enzyme Inhibitors; Drug Dosage Calculations; Drug Monitoring; Female; Glucocorticoids; Heart Failure; Humans; Hypertension; Medication Therapy Management; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Renin; Symptom Assessment

The natural history of immunoglobulin light chain associated amyloidosis (AL) is determined by the extent of cardiac involvement. Patients with cardiac AL and symptomatic heart failure have a median survival of approximately six months without successful treatment of the underlying plasma cell disorder The outcome in cardiac AL is determined by both the severity of cardiac involvement and the response to treatment. Staging systems using cardiac biomarkers, including NT- proBNP and troponin, have been found to be powerful predictors of prognosis and are used to guide treatment. Arrhythmias are common in cardiac AL and may lead to acute hemodynamic compromise. Sudden cardiac death, often due to pulseless electrical activity, is an important cause of early mortality. Supportive therapy for heart failure is usually limited to diuretics. Beta-blockers, ACE-inhibitors, and angiotensin receptor blockers are poorly tolerated in cardiac AL and should be avoided. Cardiac transplantation is controversial and reserved for highly selected patients with limited extracardiac involvement. The primary target of treatment in cardiac AL is obliteration of the plasma cell clone, using chemotherapy alone or combined with autologous stem cell transplantation. Despite the risk of early mortality, overall survival has improved with advances in disease modifying therapy. Earlier diagnosis and treatment of cardiac AL is crucial to improving survival.

Topics: Aged; Amyloidosis; Atrial Fibrillation; Biomarkers; Cardiomyopathies; Death, Sudden, Cardiac; Early Diagnosis; Female; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Embolism; Troponin

The B-type natriuretic peptides are now available on many automated clinical analysers. Clinical practice guidelines for heart failure include recommendations for where the B-type natriuretic peptides are possibly useful for clinical practice. A number of systematic reviews considering B-type natriuretic peptides in relation to heart failure patients have been published.. This review will consider the evidence presented in the systematic reviews and how this can be applied to clinical practice.. Twenty-six systematic reviews are summarised in tables considering applications to diagnostic, prognostic and guiding therapy. Important clinical considerations for these applications are discussed to facilitate appropriate implementation in the clinical laboratory.. Most clinical laboratories should be considering the appropriate implementation of the B-type natriuretic peptide as a diagnostic test to assist in ruling out heart failure. In the application of prognosis and guiding therapy a number of questions remain to be answered.

Topics: Animals; Biomarkers; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1-32, should reduce the systematic differences between methods and result in better harmonization of results.

Topics: Biomarkers; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain

Positive airway pressure (PAP) has been recognized as an effective therapeutic option for sleep-disordered breathing (SDB) in patients with heart failure (HF), and it can improve left ventricular function. Whether PAP can ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is controversial. The purpose of the present study was to quantitatively assess the efficacy of PAP on BNP in patients with HF and SDB.. A systematic search of PubMed, Embase, Web of Science and Cochrane library identified six randomized controlled trials (RCTs), in which PAP was compared with medical therapy, subtherapeutic PAP or different types of PAP. The data of BNP were extracted and pooled into meta-analysis using STATA 12.0.. Totally 6 RCT studies (7 cohorts) with 222 patients were enrolled into analysis. The quality of each study was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A significant reduction of BNP was observed after PAP treatment in patients with HF and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000).. Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of BNP in patients with HF and SDB.

Topics: Continuous Positive Airway Pressure; Heart Failure; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Sleep Apnea Syndromes

Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1), brain natriuretic peptide (BNP) and stromal cell-derived factor-1 (SDF-α), all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF). Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water.

Topics: Animals; Chemokine CXCL12; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Heart Failure; Humans; Natriuretic Peptide, Brain

To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure.. Systematic review and diagnostic meta-analysis.. Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides.. Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded.. 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0.90-0.98) to 0.97 (0.95-0.98) and a negative predictive value ranging from 0.90 (0.80-0.96) to 0.97 (0.96-0.98). At higher thresholds the sensitivity declined progressively and specificity remained variable across the range of values. There was no statistically significant difference in diagnostic accuracy between plasma B type natriuretic peptide and NTproBNP.. At the rule-out thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure, plasma B type natriuretic peptide, NTproBNP, and MRproANP have excellent ability to exclude acute heart failure. Specificity is variable, and so imaging to confirm a diagnosis of heart failure is required. There is no statistical difference between the diagnostic accuracy of plasma B type natriuretic peptide and NTproBNP. Introduction of natriuretic peptide measurement in the investigation of patients with suspected acute heart failure has the potential to allow rapid and accurate exclusion of the diagnosis.

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity

The B-type natriuretic peptide (BNP), a member of the family of vasoactive peptides, has emerged as an important diagnostic, prognostic, and therapeutic tool in patients with heart failure (HF). The rapid incorporation into clinical practice of bioassays to BNP concentrations and pharmacological agents that augment the biological actions of this peptide such as nesiritide or vasopeptidase inhibitors has shown the potential for translational research to improve patient care. Despite the indirect evidence in support of a potential benefit from raising BNP, accumulating evidence suggests that simply increasing the amount of circulating BNP does not necessarily confer cardiovascular benefits in patient with HF. Moreover, in experimental HF, the response to treatments targeting specific natriuretic peptide receptors (NPRs) signaling seems to be attenuated. A better understanding of the NPRs signaling in HF would be clinically relevant and thus required, in order to devise strategies to develop novel agents and technologies that directly target this signaling pathway.

Topics: Animals; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Drug Evaluation, Preclinical; Heart Failure; Humans; Ligands; Molecular Targeted Therapy; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Receptors, Atrial Natriuretic Factor; Signal Transduction

Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF).. We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF.. A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Benzimidazoles; Biomarkers; Biphenyl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 1; Fatty Acids, Omega-3; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Pyrimidines; Randomized Controlled Trials as Topic; Risk Factors; Rosuvastatin Calcium; Stroke; Stroke Volume; Sulfonamides; Tetrazoles

The B-type natriuretic peptide (BNP), a member of the family of vasoactive peptides, is a potent natriuretic, diuretic, and vasodilatory peptide that contributes to blood pressure and volume homeostasis. These attributes make BNP an ideal drug that could aid in diuresing a fluid-overloaded patient who had poor or worsening renal function. Despite the potential benefits of BNP, accumulating evidence suggests that simply increasing the amount of circulating BNP does not necessarily increase natriuresis in patients with heart failure (HF). Moreover, despite high BNP levels, natriuresis falls when HF progresses from a compensated to a decompensated state, suggesting the emergence of renal resistance to BNP. Although likely multifactorial, several mechanisms have been proposed to explain renal hyporesponsiveness in HF, including, but not limited to, decreased renal BNP availability, down-regulation of natriuretic peptide receptors, and altered BNP intracellular signal transduction pathways. Thus, a better understanding of renal hyporesponsiveness in HF is required to devise strategies to develop novel agents and technologies that directly restore renal BNP efficiency. It is hoped that development of these new therapeutic approaches will serve to limit sodium retention in patients with HF, which may ultimately delay the progression to overt HF.

Topics: Animals; Heart Failure; Humans; Kidney; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptides; Signal Transduction

Nesiritide, a recombinant form of B-type natriuretic peptide, is a vasodilator and currently recommended as an additive therapy for patients with acute decompensated heart failure (ADHF) who have been optimized on loop diuretics. With hospitalizations for ADHF rising, appropriate selection of therapy becomes even more important to optimize efficacy and reduce adverse events. Nesiritide has many properties that antagonize the pathophysiologic processes of heart failure and has demonstrated a comparative benefit in previous reports; however, controversy still remains with respect to its efficacy and safety. Based on results from recent clinical trials, nesiritide has been shown to be safe at currently approved doses and strongly considered for the treatment of ADHF in patients who remain symptomatic despite optimal doses of intravenous loop divertics.

Topics: Acute Disease; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Randomized Controlled Trials as Topic; Vasodilator Agents

Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction.

Topics: Aminobutyrates; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biphenyl Compounds; Clinical Trials as Topic; Drug Combinations; Heart Failure; Humans; Hypertension; Indans; Natriuretic Peptide, Brain; Neprilysin; Propionates; Pyridines; Receptors, Angiotensin; Renin-Angiotensin System; Risk Factors; Stroke Volume; Tetrazoles; Thiazepines; Valsartan

Conflicting renal effects of nesiritide have been reported in patients with acute decompensated heart failure. To answer this controversy, we performed a meta-analysis of randomized controlled trials to evaluate the influence of nesiritide on renal function in patients with acute decompensated heart failure.. Articles were obtained from PubMed, Medline, Cochrane Library and reference review. Randomized controlled studies that investigated the effects of continuous infusion of nesiritide on renal function in adult patients with acute decompensated heart failure were included and analyzed. Fixed-effect model was used to estimate relative risk (RR) and weight mean difference (WMD). The quality assessment of each study, subgroup, sensitivity, and publication bias analyses were performed.. Fifteen randomized controlled trials were eligible for inclusion. Most of included studies had relatively high quality and no publication bias was found. Overall, compared to control therapies, nesiritide might increase the risk of worsening renal function in patients with acute decompensated heart failure (RR 1.08, 95% CI 1.01-1.15, P = 0.023). In subgroup analysis, high-dose nesiritide strongly associated with renal dysfunction (RR 1.54, 95% CI 1.19-2.00, P = 0.001), but no statistical differences were observed in standard-dose (RR 1.04, 95% CI 0.98-1.12, P = 0.213), low-dose groups (RR 1.01, 95% CI 0.74-1.37, P = 0.968) and same results were identified in the subgroup analysis of placebo controlled trials. Peak mean change of serum creatinine from baseline was no significant difference (WMD -2.54, 95% CI -5.76-0.67, P = 0.121).. In our meta-analysis, nesiritide may have a dose-dependent effect on renal function in patients with acute decompensated heart failure. High-dose nesiritide is likely to increase the risk of worsening renal function, but standard-dose and low-dose nesiritide probably have no impact on renal function. These findings could be helpful to optimize the use of nesiritide in clinical practice.

Topics: Creatinine; Dose-Response Relationship, Drug; Heart Failure; Humans; Kidney; Kidney Function Tests; Models, Statistical; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Risk

Inotropes and natriuretic peptides are essential components of current therapeutic options for acute decompensated heart failure (ADHF). This systematic review examines the therapeutic effectiveness of dobutamine and brain natriuretic peptide, nesiritide, in reducing mortality and readmission rates for ADHF treatment.. Published studies related to dobutamine and nesiritide therapy in ADHF were identified via an exhaustive search of scientific literature databases. The identified studies, published between 2002 and 2012, were carefully screened based on our predefined inclusion criteria. Selected studies were pooled, and odds ratios (ORs) and 95% confidence intervals (95% CI) for each outcome were calculated. Subgroup analysis was conducted to assess the influence of ethnicity on the study outcome.. Seven cohort studies were selected for this meta-analysis. These seven studies included 959 ADHF patients who underwent nesiritide treatment and 1748 ADHF patients who received dobutamine therapy. Our meta-analysis revealed a significantly lower survival rate in dobutamine-treated patients compared with nesiritide-treated patients (OR 0.48, 95% CI 0.36-0.63, P < 0.001). Additionally, a markedly higher readmission rate was associated with dobutamine treatment compared with nesiritide treatment (OR 0.52, 95% CI 0.36-0.73, P < 0.001). A stratified analysis based on ethnicity revealed a significantly lower survival in dobutamine-treated ADHF patients in Caucasian and mixed populations compared with nesiritide treatment (Caucasian: OR 0.60, 95% CI 0.38-0.94, P = 0.024; Mixed: OR 0.38, 95% CI 0.26-0.56, P < 0.001). However, a similar association was not detected in Asian populations (P = 0.738). Further, dobutamine-treated ADHF patients displayed higher readmission rates than did nesiritide-treated patients in both Caucasian and mixed-race populations (all P < 0.05).. Our study suggests that dobutamine therapy is associated with poorer outcomes, with higher in-hospital mortality rates and increased readmission rates compared with nesiritide therapy in ADHF patients. Thus, current treatment strategies need to be redesigned for better outcomes.

Topics: Acute Disease; Cardiotonic Agents; Cohort Studies; Dobutamine; Heart Failure; Hospital Mortality; Humans; Natriuretic Peptide, Brain; Patient Readmission; Survival Analysis

Heart failure (HF) is a complex disease process that is challenging to diagnose and manage. For more than 15 years, biomarkers have been used to diagnose and the guide the management of patients with this disease. The gold standard biomarkers for HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP); both are used for diagnosis and prognosis. More recently, there has been an interest in use of BNP and NT-proBNP for HF management as well. Important aspects regarding production and clearance of BNP and NT-proBNP exist, which are vital for the clinician to understand. Beyond BNP or NT-proBNP, other newer biomarkers such as mid-regional pro-atrial natriuretic peptide, soluble ST2, highly sensitive troponin and renal biomarkers may add value for prognostication and possibly, patient management. In this article, the authors will discuss the established and evolving role of BNP and NT-proBNP in HF, along with consideration of select newer biomarkers in this setting.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

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

Biomarkers are well established for diagnosis of myocardial infarction [cardiac troponins, high-sensitivity cardiac troponins (hs-cTn)], exclusion of acute and chronic heart failure [B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP)] and venous thromboembolism (d-dimers). Several studies have demonstrated acute increases in cardiac biomarkers and altered cardiac function after strenuous sports that can pretend a cardiovascular emergency and interfere with state-of-the-art clinical assessment.. We performed a systematic review and metaanalysis of biomarker and cardiovascular imaging changes after endurance exercise. We searched for observational studies published in the English language from 1997 to 2014 that assessed these biomarkers or cardiac function and morphology directly after endurance exercise. Of 1787 identified abstracts, 45 studies were included.. Across all studies cardiac troponin T (cTnT) exceeded the cutoff value (0.01 ng/mL) in 51% (95% CI, 37%-64%) of participants. The measured pooled changes from baseline for high-sensitivity cTnT (hs-cTnT) were +26 ng/L (95% CI, 5.2-46.0), for cTnI +40 ng/L (95% CI, 21.4; 58.0), for BNP +10 ng/L (95% CI, 4.3; 16.6), for NT-proBNP +67 ng/L (95% CI, 49.9; 84.7), and for d-dimer +262 ng/mL (95% CI, 165.9; 358.7). Right ventricular end diastolic diameter increased and right ventricular ejection fraction as well as the ratio of the early to late transmitral flow velocities decreased after exercise, while no significant changes were observed in left ventricular ejection fraction.. Current cardiovascular biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) that are used in clinical diagnosis of pulmonary embolism, acute coronary syndrome, and heart failure are prone to alterations due to strenuous exercise. Hence, it is necessary to take previous physical exercise into account when a cardiac emergency is suspected.

Topics: Acute Coronary Syndrome; Biomarkers; Exercise Test; Exercise Tolerance; Fibrin Fibrinogen Degradation Products; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Troponin T

Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.. PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.. In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90-0.96), specificity of 0.91 (95% CI: 0.86-0.95), positive likelihood ratio of 10.9 (95% CI: 6.4-18.6), negative likelihood ratio of 0.07 (95% CI: 0.04-0.12), and diagnostic odds ratio of 157 (95% CI: 57-430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86-0.95), with a specificity of 0.88 (95% CI: 0.77-0.94), positive likelihood ratio of 7.8 (95% CI: 3.7-16.3), negative likelihood ratio of 0.10 (95% CI: 0.06-0.16), and diagnostic odds ratio of 81 (95% CI: 27-241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.. BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.

Topics: Atrial Natriuretic Factor; Biomarkers; Exudates and Transudates; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Pleural Effusion; Sensitivity and Specificity

Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.. To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).. The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients.

Topics: Age Factors; Aged; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Stroke Volume

Patients with advanced chronic kidney disease are at a high risk of cardiovascular events. Patients with end-stage renal disease have a particularly high morbidity and mortality, in part attributed to the complications and dysfunction related to vascular access in this population. Creation of an arteriovenous access for HD is considered standard of care for most patients and has distinct advantages including less likelihood of infections, less need for intervention, and positive impact on survival as compared with usage of a catheter. However, creation of an arteriovenous shunt incites a series of events that significantly impacts cardiovascular and neurohormonal health in both positive and negative ways. This article will review the short- and long-term effects of dialysis access on cardiovascular, neurohormonal, and pulmonary systems as well as a brief review of their effect on survival on HD. Presence of other comorbidities in a patient with dialysis access can amplify these effects, and these considerations are of paramount importance in individualizing the approach to not only the choice of vascular access but also the modality of kidney replacement therapy.

Topics: Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiac Output; Cardiovascular Diseases; Comorbidity; Heart Failure; Heart Rate; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Renal Dialysis; Vascular Resistance

This study sought to determine if amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has different diagnostic and prognostic utility in patients with renal dysfunction.. Patients with renal dysfunction have higher NT-proBNP, which may complicate interpretation for diagnosis of acute decompensated heart failure (ADHF) or prognosis.. We searched MEDLINE and EMBASE through August 2014 for studies with a subgroup analysis by renal function of the diagnostic or prognostic ability of NT-proBNP.. For diagnosis, 9 studies were included with 4,287 patients and 1,325 ADHF events. Patients were mostly divided into subgroups with and without renal dysfunction by an estimated glomerular filtration rate of 60 ml/min/1.73 m(2). In patients with renal dysfunction, the area under the curve (AUC) for NT-proBNP ranged from 0.66 to 0.89 with a median cutpoint of 1,980 pg/ml, while the AUC ranged from 0.72 to 0.95 with a cutpoint of 450 pg/ml in patients with preserved renal function. For prognosis, 30 studies with 32,203 patients were included, and mortality in patients with renal dysfunction (25.4%) was twice that of patients with preserved renal function (12.2%). The unadjusted pooled risk ratio for NT-proBNP and mortality was 3.01 (95% confidence interval [CI]: 2.53 to 3.58) in patients with preserved renal function and was similar in patients with renal dysfunction (3.25; 95% CI: 2.45 to 4.30). Upon meta-regression, heterogeneity was partially explained if patients with heart failure or coronary artery disease were enrolled.. NT-proBNP retains utility for diagnosis of ADHF in patients with renal dysfunction with higher cutpoints. Elevated NT-proBNP confers a worse prognosis regardless of renal function.

Topics: Biomarkers; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis

A biomarker is any measurable, surrogate characteristic, which reflects either the presence or the absence of a disease state. This can be a blood test, an imaging characteristic, an exercise parameter, and even a genetic profile. Serum biomarkers are particularly attractive in that their cost to the patient is relatively low in terms of money, time, risk, and ease of obtaining a sample. The potential benefits of a good biomarker are manifold. This manuscript will review serum biomarkers of proposed utility in paediatric heart failure, especially with respect to their ability to aid clinical decision making, diagnosis, and prognosis.

Topics: Adolescent; Biomarkers; Child, Preschool; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin I; Troponin T

The increasing use of cardiac biomarkers in the diagnosis and management of heart failure (HF) has led to their inclusion in clinical practice guidelines. Studies have demonstrated that natriuretic peptides and cardiac troponins are useful adjuncts in identifying patients with HF at high risk, and we now know that a number of factors influence biomarker levels, including age, renal failure, obesity, and comorbid conditions, and that these factors as well as biomarker assay variability need to be considered when interpreting the results of biomarker testing. The broader use of cardiac biomarker testing has been limited by the lack of consistent data to support a benefit of their use in triaging management decisions, and the majority of drug therapies and titration schedules for HF were developed prior to the availability of biomarkers. Nevertheless, natriuretic peptide testing has been widely adopted, with recent guidelines supporting its use in the diagnosis of acute HF, especially in the setting of clinical uncertainty, as well as in assessing disease severity and prognosis. This review summarizes the data on traditional cardiac biomarkers and describes how the latest investigations have shaped the recommendations in the latest clinical practice guidelines.

Topics: Biomarkers; C-Reactive Protein; Disease Management; Galectin 3; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Troponin

Heart failure (HF) with preserved ejection fraction (HFPEF) is an increasingly prevalent clinical syndrome with many unresolved issues regarding diagnosis, pathophysiology, and treatment. The major pathophysiological mechanisms underlying HFPEF are known to be fibrosis and reduced ventricular compliance, and hypertension (HTN) is perhaps the most significant risk factor for the development of left ventricular diastolic dysfunction (LVDD). Inflammation is one of the earliest events in cardiac stress situations such as pressure and/or volume overload and involves elevated levels of endothelial adhesion molecules as well as increased production and release of inflammatory cytokines and chemokines in the tissue. The latter promotes the infiltration of activated inflammatory cells, particularly monocytes, into the cardiac tissue. Increased monocyte infiltration is seen in the early and late stages of HTN and HFPEF. Once inside the tissue, monocytes differentiate into macrophages and promote cardiac inflammation, tissue injury, and myocardial fibrosis. This review focuses on inflammation as the initial and primary trigger of ventricular remodelling in HTN and LVDD, affecting progression to HFPEF. The link between inflammation and b-type natriuretic peptide (BNP), a clinical marker of cardiac pressure overload which is positively associated with cardiac dysfunction and HF, is also described. Finally, current and prospective therapeutic approaches for HFPEF based on modification of the inflammatory response are reviewed.

Topics: Heart Failure; Heart Ventricles; Humans; Inflammation; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Models to stratify risk for patients hospitalised for acute decompensated heart failure (ADHF) do not include the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels during hospitalisation.. The aim of our study was to develop a simple yet robust discharge prognostication score including NT-proBNP for this notorious high-risk population.. Individual patient data meta-analyses of prospective cohort studies.. Seven prospective cohorts with in total 1301 patients.. Our study population was assembled from the seven studies by selecting those patients admitted because of clinically validated ADHF, discharged alive, and NT-proBNP measurements available at admission and at discharge.. The endpoints studied were all-cause mortality and a composite of all-cause mortality and/or first readmission for cardiovascular reason within 180 days after discharge.. The model that incorporated NT-proBNP levels at discharge as well as the changes in NT-proBNP during hospitalisation in addition to age ≥75 years, peripheral oedema, systolic blood pressure ≤115 mm Hg, hyponatremia at admission, serum urea of ≥15 mmol/L and New York Heart Association (NYHA) class at discharge, yielded the best C-statistic (area under the curve, 0.78, 95% CI 0.74 to 0.82). The addition of NT-proBNP to a reference model significantly improved prediction of mortality as shown by the net reclassification improvement (62%, p<0.001). A simplified model was obtained from the final Cox regression model by assigning weights to individual risk markers proportional to their relative risks. The risk score we designed identified four clinically significant subgroups. The pattern of increasing event rates with increasing score was confirmed in the validation group (BOT-AcuteHF, n=325, p<0.001).. In patients hospitalised for ADHF, the addition of the discharge NT-proBNP values as well as the change in NT-proBNP to known risk markers, generates a relatively simple yet robust discharge risk score that importantly improves the prediction of adverse events.

Topics: Acute Disease; Aged; Aged, 80 and over; Cohort Studies; Disease Progression; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment

Acute decompensated heart failure (ADHF) is associated with substantial morbidity and mortality, and represents a considerable financial burden to society. Historically, few prospective, randomized, double-blinded trials have investigated the optimal management of ADHF, and most guideline recommendations are based primarily on expert opinion. However, in the last decade, a considerable amount of research has added to the understanding of the management of ADHF in both patients with fluid overload and low cardiac output. In addition, as mechanical circulatory support devices and heart transplantation continue to evolve, significant advances have also been made with regard to the proper selection of patients for advanced surgical options. Finally, several novel pharmacologic agents have shown promise in early trials and may represent the next steps in ADHF management. Although advances have been made over the past decade, many questions remain.

Topics: Acute Disease; Diuretics; Dopamine; Heart Failure; Heart Transplantation; Humans; Natriuretic Peptide, Brain; Nitroprusside; Ultrafiltration; Vasodilator Agents; Vasopressins

The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B-type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT-proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BNP and NT-proBNP relative to therapeutic intervention in HF has led to the concept of using the biomarkers as a 'guide' for intensification of HF care with a goal of not only achieving guideline-directed medical therapy goals accompanied by targeted natriuretic peptide suppression below prognostic thresholds. In studies achieving this combination of therapy optimization and BNP/NT-proBNP suppression, superior outcomes have been observed, and the approach was well tolerated. Natriuretic peptide-guided HF therapy has recently been given a recommendation in US HF guidelines to achieve guideline-directed medical therapy (Class IIa) and possibly improve outcome (Class IIb), while other clinical practice guidelines (including those from the European Society of Cardiology) await results from emerging clinical trial data. We will review lessons learned in the past regarding this novel concept of biomarker guided HF care, and discuss future directions for the approach.

Topics: Age Factors; Ambulatory Care; Biomarkers; Clinical Trials as Topic; Cost-Benefit Analysis; Forecasting; Heart Failure; Humans; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Prognosis; Risk Factors; Stroke Volume; Time Factors; Ventricular Dysfunction, Left

This review will provide an overview of recent advances in the management of acute decompensated heart failure, focusing on major publications from the past few years.. There have been several publications investigating different strategies in the management of acute decompensated heart failure. Trials have investigated the role of ultrafiltration, diuretic infusions and recombinant B-type natriuretic peptide for the treatment of these patients.. In patients with acute decompensated heart failure, the use of ultrafiltration in place of diuretics, diuretic infusions, and B-type natriuretic peptide has not shown benefit in recent trials. Unfortunately, there have been no major advances in the management of patients with acute decompensated heart failure.

Topics: Acute Disease; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain; Ultrafiltration

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function.

Topics: Atrial Natriuretic Factor; Diuretics; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Glomerulus; Kidney Tubules; Natriuretic Peptide, Brain; Renal Circulation; Renal Insufficiency, Chronic; Sodium; Water-Electrolyte Imbalance

The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with heart failure caused by various acquired and congenital heart diseases (CHD). In January 2013, we performed a computerized literature search in the National Library of Medicine (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included a mix of Medical Subject Headings and free-text terms for the key concepts, starting from BNP assay and 'NT-proBNP assay', children, CHD. The search was further refined by adding the keywords neonate/s, newborn/s, heart failure, cardiomyopathy, screening, prognosis, follow-up, and management. BNP values are age and method dependent, even in pediatric populations. Regardless of age, there is great variability in BNP/NT-proBNP values within CHD characterized by different hemodynamic and clinical conditions. There is enough evidence to support the use of BNP/NT-proBNP as an adjunctive marker in the integrated evaluation of patients with congenital and acquired heart disease to help define severity and progression of heart failure as well in the monitoring of response to treatment. BNP/NT-proBNP can also be used for the screening of heart failure and as a prognostic marker in children undergoing cardiac surgery; however, to date, there are studies with heterogeneous patient groups, and diverse outcome measures selected are still few. BNP/NT-proBNP can be used as adjunctive markers in the integrated screening, diagnosis, management, and follow-up of children with heart failure caused by various acquired and congenital heart disease.

Topics: Biomarkers; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are the gold standard biomarkers in determining heart failure (HF) diagnosis and prognosis. These natriuretic peptides may also be useful in guiding HF management, but further studies are needed before they can be routinely recommended for that purpose. A novel natriuretic peptide biomarker, mid-regional pro atrial natriuretic peptide (MR-proANP), shows promise in determining diagnosis and prognosis in HF patients. BNP and NT-proBNP may be of use in excluding myocardial infarction and to assist in determining prognosis in acute coronary syndrome (ACS). Therapeutic implication of natriuretic peptides in ACS is unclear.

Topics: Acute Coronary Syndrome; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis

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

Heart failure (HF) is a prevalent disease that is associated with a high morbidity and mortality; HF is estimated to cost the US healthcare system over US$39 billion annually. Biomarkers have an increasingly important role in achieving management goals through rapid diagnosis and monitoring of disease processes. HF is a target for healthcare cost control measures and quality improvement metrics. In achieving these benchmarks, point-of-care testing, the development of more sensitive assays for traditional biomarkers and determining appropriate applications for novel markers will be essential in meeting these health quality and cost-driven metrics. Point-of-care applications involving biomarkers can be utilized in inpatient, outpatient and emergency department settings to aid in the rapid diagnosis, risk stratification and management of patients presenting with symptoms consistent with HF. In this paper we review current and promising HF biomarkers with an emphasis on point-of-care testing and its implications in the changing healthcare landscape.

Topics: Aged; Biomarkers; Cardiology; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Point-of-Care Systems; Troponin

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

In this review, heart failure is confined to etiologies not due to rhythm disturbances or valvular heart disease. Besides measurement of natriuretic peptides, echocardiography is established as an important diagnostic procedure. Echocardiography is especially helpful in discriminating between heart failure with preserved ejection fraction (HF-PEF) and reduced ejection fraction (HF-REF). Because of its ease to be performed, the 6 min walk test continues to be a standard diagnostic procedure. Cardiopulmonary exercise testing provides more detailed information regarding differential diagnostic and prognostic considerations.

Topics: Biomarkers; Echocardiography; Electrocardiography; Exercise Test; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume

Topics: Biomarkers; Child; Child, Preschool; Critical Illness; Early Diagnosis; Heart Failure; Humans; Infant; Intensive Care Units; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Heart Disease; Risk Assessment; Sepsis; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Biomarkers; Cardiology; Gene Expression; Heart Failure; Humans; Immunoassay; Japan; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Reference Values; Renin-Angiotensin System; Societies, Medical

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

Several aggregate data meta-analyses suggest that treatment guided by the serum concentration of natriuretic peptides (B-type natriuretic peptide (BNP) or its derivative N-terminal pro-B-type natriuretic peptide (NT-BNP)) reduces all-cause mortality compared with usual care in patients with heart failure (HF). We propose to conduct a meta-analysis using individual participant data (IPD) to estimate the effect of BNP-guided therapy on clinical outcomes, and estimate the extent of effect modification for clinically important subgroups.. We will use standard systematic review methods to identify relevant trials and assess study quality. We will include all randomized controlled trials (RCTs) of BNP-guided treatment for HF that report a clinical outcome. The primary outcome will be time to all-cause mortality. We will collate anonymized, individual patient data into a single database, and carry out appropriate data checks. We will use fixed-effects and random-effects meta-analysis methods to combine hazard ratios (HR) estimated within each RCT, across all RCTs. We will also include a meta-analysis and meta-regression analyses based on aggregate data, and combine IPD with aggregate data if we obtain IPD for a subset of trials.. The IPD meta-analysis will allow us to estimate how patient characteristics modify treatment benefit, and to identify relevant subgroups of patients who are likely to benefit most from BNP-guided therapy. This is important because aggregate meta-analyses have suggested that clinically relevant subgroup effects exist, but these analyses have been unable to quantify the effects reliably or precisely.. PROSPERO 2013: CRD42013005335.

Topics: Biomarkers, Pharmacological; Cardiotonic Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Systematic Reviews as Topic

Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome.

Topics: Acute Disease; Amides; Benzazepines; Cardio-Renal Syndrome; Dobutamine; Fumarates; Heart Failure; Humans; Hydrazones; Inflammation; Kaplan-Meier Estimate; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Prognosis; Pyridazines; Randomized Controlled Trials as Topic; Recombinant Proteins; Relaxin; Simendan; Therapies, Investigational; Tolvaptan

The natriuretic peptide (NP) family includes atrial (ANP), brain or B-type (BNP) and C-type NP (CNP). A huge number of experimental and clinical studies, published in the 1st decade of this century, have added further support to the hypothesis that endocrine function in the human heart is a relevant component of a complex network including endocrine, nervous and immune systems. The NP hormones constitute a well-integrated regulatory system and share a similar spectrum of biological actions, although there are some differences in biological potency between ANP, BNP and CNP. However, several important issues on this field need to be investigated further. The production, secretion and peripheral degradation pathways of both BNP and CNP should be clarified in detail. In particular, the hypothesis that the circulating plasma pool of the prohormone can function as a precursor of the active peptide hormone should be demonstrated definitively. Recent findings indicate that peripheral processing of circulating prohormones could likely be submitted to regulatory rules, which might be impaired in patients with heart failure, opening up new perspectives even in the treatment of heart failure. This hypothesis suggests a novel pharmacological target for drugs inducing and/or modulating the maturation of the prohormone into active hormone.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Heart; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels are increased in persons with heart failure (HF); low levels of these peptides rule out HF. We systematically reviewed the literature to assess the use of BNP and NT-proBNP in the diagnosis, prognosis, and treatment for HF. We also examined the biological variation of these peptides in persons with and without HF. We searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language studies published between January 1989 and June 2012. Supplemental searches involved the gray literature and the reference lists of included studies. Trained reviewers used standardized forms to screen articles for inclusion in the review and to extract data from included papers. We examined the risk of bias with QUADAS-2 for diagnosis studies, the Hayden criteria for prognosis studies, and the Jadad scale for treatment studies. We assessed the strength of evidence in four domains (risk of bias, consistency, directness, and precision) for the diagnosis and treatment studies. Results were reported as narrative syntheses. Additional meta-analyses were conducted for the diagnosis studies. Three hundred ten articles passed through screening and were included in the review. One hundred four articles applied to diagnostic accuracy, 190 papers pertained to prognosis, and nine articles addressed BNP- or NT-proBNP-guided treatment. Each individual paper in this series reports, summarizes, and discusses the evidence regarding diagnosis, prognosis, or treatment.

Topics: Disease Management; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors

Our purpose was to determine the test performance characteristics of BNP and NT-proBNP in the diagnosis of heart failure for patients presenting to an emergency department or urgent care center. We searched Medline, Embase, AMED, Cochrane, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published between 1989 and June 2012. Studies were limited to those using FDA-approved assays. We examined test performance at three pre-specified cutpoints (manufacturers' suggested, researchers' optimal, and lowest) and considered the effect of age, gender, ethnicity and renal function. We used the QUADAS-2 tool to examine risk of bias and applicability, and the AHRQ Methods Guide to assess the strength of evidence. Seventy-six articles met our inclusion criteria, 37 examined BNP, 25 examined NT-proBNP, and 14 examined both. Pooled sensitivity and specificity for BNP at the three pre-specified cutpoints were 95, 91, and 95 % (sensitivity) and 55, 80, and 67 % (specificity), respectively. For NT-proBNP, sensitivity and specificity at the same cutpoints were 91, 90, and 96 % (sensitivity) and 67, 74, and 55 % (specificity). Both BNP and NT-proBNP perform well to rule out, but less well to rule in, the diagnosis of heart failure among persons presenting to emergency departments or urgent care centers. Both BNP and NT-proBNP levels are positively associated with age and negatively associated with renal function. However, the effect of these factors with respect to selecting optimal cutpoints is unclear. For BNP, 100 pg/mL appears to be a consensus cutpoint. No clear consensus has emerged for NT-proBNP, but the age-adjusted cutpoints of 450 pg/mL for <50 years, 900 pg/mL for 50-75 years and 1,800 pg/mL for >75 years appear promising and merit greater scrutiny and validation.

Topics: Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Nesiritide and dopamine have been recognized for some time as potential renal adjunct therapies in the management of patients with acute heart failure (AHF). Several studies have yielded conflicting evidence of the efficacy of both medications in enhancing the renal function of patients with AHF. The Renal Optimization Strategies Evaluation (ROSE) study was a multicenter double-blind placebo controlled trial designed to assess the potential renoprotective effects of low-dose nesiritide and dopamine in AHF patients with renal dysfunction. This article will focus on previous research, summary of results, and lessons learned from the ROSE-AHF trial as well as future directions for clinical research and applications.

Topics: Acute Kidney Injury; Disease Progression; Dose-Response Relationship, Drug; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Stroke Volume; Treatment Outcome

National and international guidelines have been published recommending the use of natriuretic peptides as an aid to the diagnosis of heart failure (HF) in acute settings; however, few specific recommendations exist for governing the use of these peptides in primary care populations. To summarize the available data relevant to the diagnosis of HF in primary care patient population, we systematically reviewed the literature to identify original articles that investigated the diagnostic accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in primary care settings. The search yielded 25,864 articles in total: 12 investigating BNP and 20 investigating NT-proBNP were relevant to our objective and included in the review. QUADAS-2 and GRADE were used to assess the quality of the included articles. Diagnostic data were pooled based on three cutpoints: lowest and optimal, as chosen by study authors, and manufacturers' suggested. The effect of various determinants (e.g., age, gender, BMI, and renal function) on diagnostic performance was also investigated. Pooled sensitivity and specificity of BNP and NT-proBNP using the lowest [0.85 (sensitivity) and 0.54 (specificity)], optimal (0.80 and 0.61), and manufacturers' (0.74 and 0.67) cutpoints showed good performance for diagnosing HF. Similar performance was seen for NT-proBNP: lowest (0.90 and 0.50), optimal (0.86 and 0.58), and manufacturers' (0.82 and 0.58) cutpoints. Overall, we rated the strength of evidence as high because further studies will be unlikely to change the estimates diagnostic performance.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Primary Health Care

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

Prognosis permits clinicians to separate persons with heart failure (HF) into subgroups based on likely health outcomes. Treatment is partly guided by these likely outcomes. This systematic review explores whether brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are independent predictors of prognosis in persons with chronic stable HF. We electronically searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published between 1989 and mid-2012. We utilized trained reviewers and standardized forms to screen articles for inclusion and extracted data from included articles. All included studies were summarized in narrative and tabular form. We used the Hayden criteria to assess the risk of bias. Sixteen BNP publications and 88 NT-proBNP publications were included in the systematic review. BNP was positively associated with all-cause and HF mortality. NT-proBNP was positively associated with all-cause and cardiovascular mortality. BNP and NT-proBNP levels are useful for estimating prognosis in persons with chronic stable HF. Further research is required to establish optimal cutpoints and to assess whether prognostic effects differ by age, sex, or time period.

Topics: Cause of Death; Global Health; Heart Failure; Humans; Morbidity; Natriuretic Peptide, Brain; Peptide Fragments

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach.

Topics: Biomarkers; Cardiotonic Agents; Drug Monitoring; Echocardiography; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Systems Integration

The aim of this systematic review was to determine whether B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) independently add incremental value for predicting mortality and morbidity in patients with acute decompensated heart failure (ADHF). Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL were searched from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for risk of bias. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. From 183 citations, only seven studies (5 BNP and 2 NT-proBNP) considered incremental value in ADHF subjects admitted to acute care centers. Admission assay levels and length of follow-up varied for BNP studies (31 days to 12 months) and for NT-proBNP studies (25-82 months). All studies presented at least one estimate of incremental value of BNP/NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that BNP or NT-proBNP increased model performance. Three studies used reclassification and model validation computations to establish incremental value; these studies showed less consistency with respect to added value. In conclusion, the literature assessing incremental value of BNP/NT-proBNP in ADHF populations is limited to seven studies evaluating only mortality outcomes and at moderate risk of bias. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in BNP/NT-proBNP adding incremental value in prediction models in ADHF patients.

Topics: Acute Disease; Biomarkers; Global Health; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Survival Rate

The use of B-type natriuretic peptides to predict outcomes in general populations has been investigated in a number of primary studies. A previous systematic review considering natriuretic peptides in cardiovascular disease included a subgroup of general population studies, which suggested an association with a number of clinical outcomes. We electronically searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published between 1989 and mid-2012. We utilized trained reviewers and standardized forms to screen articles for inclusion and extract data from included articles. All included studies (n = 7) were summarized in narrative and tabular form. A general population was defined as one that was randomly selected from a community setting where no specific inclusion or exclusion criteria were specified. The seven included studies all used FDA approved assays for NT-proBNP. The range of clinical outcomes and heterogeneity did not allow for meta-analysis. The hazard ratios for predicting outcomes in the included studies ranged from 1.0 to 4.1 (all p values <0.05). The discrimination statistics reported in four studies all demonstrated statistically significant improvements in predicting outcomes. NT-proBNP is associated with heart failure, all-cause and cardiovascular mortality, and other combined cardiovascular events in a general unselected population. The discrimination statistics suggest modest improvements in risk stratification. No prospective studies exist to demonstrate the clinical utility of using B-type natriuretic peptides to predict clinical outcomes in a general population.

Topics: Disease Management; Global Health; Heart Failure; Humans; Morbidity; Natriuretic Peptide, Brain; Prognosis; Survival Rate

A systematic review was undertaken to examine the evidence for B-type natriuretic peptides (BNP and NT-proBNP) as independent predictors of mortality, morbidity, or combined mortality and morbidity outcomes in persons with acute decompensated heart failure (ADHF). Electronic databases (Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL) were searched from 1989 to June 2012. Reference lists of included articles, systematic reviews, and the gray literature were also searched. English language studies were eligible if they included subjects with ADHF and measured BNP/NT-proBNP using FDA approved assays. Standardized forms were used to select studies, extract data, and assess risk of bias. Seventy-nine studies, ranging over followup intervals from 14 days to 7 years, evaluating levels of BNP (n = 38), NT-proBNP (n = 35), or both (n = 6) were eligible. The majority of studies predicted mortality outcomes for admission BNP/NT-proBNP levels, with fewer studies evaluating serial, change from admission, or discharge levels. In general, higher levels of admission BNP or NT-proBNP predicted greater risk for all outcomes. Decreased levels post-admission predicted decreased risk. Overall, these studies were rated as having moderate risk of bias. This systematic review shows that BNP and NT-proBNP are independent predictors of mortality (all-cause and cardiovascular) in ADHF despite different cutpoints, time intervals, and prognostic models. Findings for morbidity and composite outcomes were less frequently evaluated and showed inconsistency. Further research is required to assess cutpoints for admission, serial measurements, change following admission, and discharge levels to assist clinical decision-making.

Topics: Global Health; Heart Failure; Humans; Morbidity; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Survival Rate

BNP/NT-proBNP measurement has not gained widespread use for the management of patients with heart failure (HF) despite several randomized controlled trials. A systematic review addressing the question of whether patients with HF benefit from BNP-assisted therapy or intensified therapy compared with usual care was undertaken. Relevant randomized controlled trial (RCTs) were selected by searching Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published from 1980 to 2012. Selected studies required patients to be treated for chronic HF with medical therapy based on BNP/NT-proBNP or usual care. There were no restrictions except that BNP/NT-proBNP measurement had to be done by an FDA approved method. Nine RCTs were identified with 2,104 patients with study duration that ranged from 3 to 18 months. Overall, there was a wide variation in study design and how parameters were reported including patient selection, baseline characteristics, therapy goals, BNP/NT-proBNP cutpoint, and outcome types. Meta-analysis was not appropriate given this study heterogeneity. The strength of evidence for the outcome of mortality, reported in seven studies, was found to be low due to inconsistency and imprecision. This systematic review showed that the evidence is of low quality and insufficient to support the use of BNP/NT-proBNP to guide HF therapy. Further trials with improved design are needed.

Topics: Disease Management; Heart Failure; Humans; Natriuretic Peptide, Brain; Treatment Outcome

Acute heart failure is a major cause of emergency hospital admission, with significant impact on health resources and patient outcomes. With no new treatments for over 20 years, the advent of new innovative therapies may facilitate a radical change in our approach to such patients. In this article, we examine the current evidence for the use of current intravenous vasodilators in AHF management, and review the potential of novel therapies currently in development.

Topics: Acute Disease; Administration, Intravenous; Atrial Natriuretic Factor; Benzoates; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Nitrates; Peptide Fragments; Recombinant Proteins; Relaxin; Snake Venoms; Vasodilator Agents

Acute heart failure (AHF) is a major health problem worldwide, with no proven therapy. Low-dose dopamine has been used in this entity to improve renal outcomes in the past decades. The aim of this article is to review the former and recent clinical trials about the use of low-dose dopamine in AHF.. The Dopamine in Acute Decompensated Heart Failure II study enrolled 161 patients with AHF and found no improvement in clinical outcomes with the addition of dopamine. Similarly, the Renal Optimization Strategies Evaluation in Acute Heart Failure trial, which included 360 patients with AHF and renal dysfunction, evaluated the efficacy of 72-h infusion of either low-dose nesiritide or low-dose dopamine versus placebo in addition to standardized diuretic treatment. No differences were found between both treatment groups and placebo with regard to the coprimary endpoints of cumulative urine volume and change from baseline in plasma cystatin C.. On the basis of the current data, there is no role for the routine use of low-dose dopamine in nonhypotensive patients with AHF. Further studies are needed to define the role of low-dose dopamine in patients with AHF and hypotension. Until the availability of more data, the use of dopamine in AHF should be individualized.

Topics: Cardiotonic Agents; Cystatin C; Diuretics; Dopamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Heart Failure; Humans; Infusions, Intravenous; Kidney; Kidney Diseases; Kidney Function Tests; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Treatment Outcome; United States

Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-type natriuretic peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationship between BNP and NT-proBNP levels and myocardial stiffness is complex. Recent data suggest an inverse relationship between BNP and NT-proBNP levels and body mass index. Given the ever-increasing prevalence of obesity world-wide, it is important to understand the benefits and limitations of HF biomarkers in this population. This review will explore the biology, physiology, and pathophysiology of these peptides and the cardiac endocrine paradox in HF. We also examine the clinical evidence, mechanisms, and plausible biological explanations for the discord between BNP levels and HF in obese patients.

Topics: Biomarkers; Body Mass Index; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Prognosis

Because of heart-lung interactions, weaning from mechanical ventilation induces strong hemodynamic changes that can lead to weaning-induced cardiac failure. Cardiac patients are particularly at risk for this complication. In this review, we will summarize the most recent advances concerning the mechanisms, diagnosis and treatment of weaning-induced cardiac failure.. The role of left ventricular diastolic abnormalities contributing to weaning-induced pulmonary edema has been recently emphasized. The most important recent findings concern the diagnostic tools that can be used as alternatives to the pulmonary artery catheter for detecting weaning-induced pulmonary edema during a spontaneous breathing trial, such as increase in estimates of left ventricular filling pressure with echocardiography, increase in B-type natriuretic peptide, increase in plasma protein and hemoglobin concentration and increase in extravascular lung water measured by transpulmonary thermodilution. Concerning the treatment, recent data suggest that fluid removal, which is often indicated in such instances, could be guided by the dosage of B-type natriuretic peptide.. Nowadays, the diagnosis of weaning-induced pulmonary edema can be easily made. Identifying such an event is important as an appropriate treatment, guided by the suspected mechanisms leading to the cardiac failure, should hasten weaning from mechanical ventilation.

Topics: Catheterization, Swan-Ganz; Echocardiography; Heart Failure; Hemodynamics; Humans; Intensive Care Units; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Predictive Value of Tests; Pulmonary Edema; Respiration, Artificial; Risk Assessment; Ventilator Weaning

Topics: Acute Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Treatment Failure

This study sought to review the literature for risk prediction models in patients with heart failure and to identify the most consistently reported independent predictors of risk across models.. Risk assessment provides information about patient prognosis, guides decision making about the type and intensity of care, and enables better understanding of provider performance.. MEDLINE and EMBASE were searched from January 1995 to March 2013, followed by hand searches of the retrieved reference lists. Studies were eligible if they reported at least 1 multivariable model for risk prediction of death, hospitalization, or both in patients with heart failure and reported model performance. We ranked reported individual risk predictors by their strength of association with the outcome and assessed the association of model performance with study characteristics.. Sixty-four main models and 50 modifications from 48 studies met the inclusion criteria. Of the 64 main models, 43 models predicted death, 10 hospitalization, and 11 death or hospitalization. The discriminatory ability of the models for prediction of death appeared to be higher than that for prediction of death or hospitalization or prediction of hospitalization alone (p = 0.0003). A wide variation between studies in clinical settings, population characteristics, sample size, and variables used for model development was observed, but these features were not significantly associated with the discriminatory performance of the models. A few strong predictors emerged for prediction of death; the most consistently reported predictors were age, renal function, blood pressure, blood sodium level, left ventricular ejection fraction, sex, brain natriuretic peptide level, New York Heart Association functional class, diabetes, weight or body mass index, and exercise capacity.. There are several clinically useful and well-validated death prediction models in patients with heart failure. Although the studies differed in many respects, the models largely included a few common markers of risk.

Topics: Age Factors; Blood Pressure; Body Mass Index; Comorbidity; Decision Support Techniques; Diabetes Mellitus; Exercise Tolerance; Female; Heart Failure; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Severity of Illness Index; Sex Factors; Sodium

Increased neurohormonal activation is a key feature of heart failure (HF). Copeptin is a surrogate marker for proarginine vasopressin and the prognostic value of copeptin has been reported for multiple disease states of both nonvascular and cardiovascular etiology. Elevated plasma copeptin in HF has been associated with adverse outcomes such as increased mortality, risk of hospitalization and correlates with the severity of HF. Copeptin may add prognostic information to already established predictors such as clinical variables and natriuretic peptides in HF. In addition, copeptin has been found to be a superior marker when compared with BNP and NT-proBNP in HF patients discharged after hospitalization caused by HF or myocardial infarction (MI). The optimal use of copeptin in HF remains unresolved and future appropriately sized and randomized trials must determine the role of copeptin in HF as a marker of adverse outcomes, risk stratification or as a target in biomarker-guided therapy with arginine vasopressin-antagonists in individualized patient treatment and everyday clinical practice.

Topics: Arginine Vasopressin; Biomarkers; Glycopeptides; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Precision Medicine; Severity of Illness Index

Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat, and LCZ696. Although ecadotril, candoxatril, and omapatrilat were initially tested in hypertension and/or heart failure, lack of efficacy and side effects led to discontinuation of their development. LCZ696 (sacubitril valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that has been developed for use in heart failure. This compound is composed of 2 molecular moieties in a single crystalline complex-the angiotensin receptor blocker valsartan and a neprilysin inhibitor prodrug-and has now been tested in hypertension, in a phase 2 trial in heart failure with preserved ejection fraction, and has demonstrated greater efficacy than enalapril in a phase 3 trial in heart failure with reduced ejection fraction. Its ability to inhibit the renin-angiotensin-aldosterone axis and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Biomarkers; Biphenyl Compounds; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System; Tetrazoles; Valsartan

Topics: Biological Factors; Heart Failure; Humans; Natriuretic Peptide, Brain; Neprilysin; Randomized Controlled Trials as Topic; Renin-Angiotensin System

The effect of natriuretic peptides on cardiovascular and renal system offers a potential benefit in therapy of hypertension and heart failure; however the current results of clinical trials are not encouraging. Synthetic B natriuretic peptide has demonstrated short-term hemodynamic improvement in patients, but in terms of renal function and long-term prognosis the effect was questionable. Nevertheless, new hope is ularitid a dual inhibitor of neprilysin and ARB: LCZ 696, the ongoing clinical studies and previous data from pilot studies appear promising.

Topics: Animals; Cardiovascular System; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Recombinant Proteins

Heart failure (HF) often presents as dyspnea either with exertion and/or recumbency. Patients also experience dependent swelling and fatigue. Measurement of the left ventricular ejection fraction (LVEF) identifies HF patients who may respond to pharmacologic therapy and/or electrophysiologic device implantation. Angiotension converting enzyme inhibitors, beta blockers, and aldosterone inhibitors can significantly lower the mortality and morbidity of HF in patients with an LVEF less than 35%. Cardiac defibrillators and biventricular pacemakers can also improve outcomes in selected patients with a decreased LVEF. The authors provide a guide for therapeutic decisions based on the inclusion criteria of the major clinical trials.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Cardiac Surgical Procedures; Cardiovascular Agents; Comorbidity; Complementary Therapies; Defibrillators, Implantable; Electrocardiography; Health Behavior; Heart Failure; Humans; Life Style; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Patient Education as Topic; Primary Health Care; Randomized Controlled Trials as Topic; Stroke Volume

Natriuretic neuropeptides (ANP, BNP, CNP) are produced primarily in the cardiac atria under normal conditions. The main stimulus for ANP and BNP peptide synthesis and secretion is cardiac wall stress. Cardiac ventricular myocytes constitute the major source of BNP-related peptides. Ventricular NT-proBNP production is upregulated in cardiac failure and locally in the area surrounding a myocardial infarct. NT-proBNP is cleared passively by organs with high rate of blood flow (muscle, liver, kidney). It has a longer half life than BNP and higher plasma concentration. BNP and NTproBNP tend to be higher in women and lower in obese individuals. They are also higher in elderly, in left ventricular tachycardia, right ventricular overload, myocardial ischemia, hypoxaemia, renal dysfunction, liver cirrhosis, sepsis and infection. NT-proBNP is useful both in the diagnosis and prognosis of heart failure and is considered to be a gold standard biomarker in heart failure similar to BNP. A cut-off point 300 pg/ml has 99% sensitivity, 60%specificity and NPV 98%for exclusion of acute heart failure. NT proBNP has also a strong prognostic value of death in acute and chronic heart failure and also predicts short and long term mortality in patient with suspected or confirmed unstable CVD. Natriuretic peptides are also prognostic markers for the RV (Right Ventricular) Dysfunction. Their release is due to myocardial stretch from right ventricular pressure overload.Finally, there are data supporting that NT-proBNP might be useful to put a time frame on atrial fibrillation of unknown onset.

Topics: Amino Acid Sequence; Atrial Fibrillation; Biomarkers; Coronary Artery Disease; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Male; Molecular Sequence Data; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Ventricular Dysfunction, Right

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

Light's criteria combine three dichotomous tests into a decision rule that is considered positive if any one of the tests is positive. This strategy clearly maximizes sensitivity, although at the expense of specificity. Although Light's criteria identify 98% of pleural exudates, they misclassify about 25% of transudates as exudates. The way to overcome this limitation is discussed in this review.. Traditionally, measurement of the protein gradient between the serum and pleural fluid has been recommended to decrease the misclassification rate of Light's criteria. A recent study demonstrated that a gradient between the albumin levels in the serum and the pleural fluid more than 1.2 g/dl performs significantly better than a protein gradient more than 3.1 g/dl to correctly categorize mislabeled cardiac effusions (83 vs. 55%). On the other hand, the accuracy of a pleural fluid to serum albumin ratio less than 0.6 excelled when compared with albumin and protein gradients in patients with miscategorized hepatic hydrothoraces (77 vs. 62 vs. 61%).. The simplest strategy to reveal the true transudative nature of heart failure-related effusions, labeled as exudates by Light's criteria, is to calculate the serum to pleural fluid albumin gradient. Conversely, for misclassified hepatic hydrothoraces, measurement of the pleural to serum albumin ratio is recommended. The serum to pleural fluid protein gradient should no longer be considered the preferred test for this purpose.

Topics: Exudates and Transudates; Female; Heart Failure; Humans; Hydrothorax; L-Lactate Dehydrogenase; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Effusion; Reproducibility of Results; Serum Albumin; Staining and Labeling

It is unclear whether postoperative B-type natriuretic peptides (i.e., BNP and N-terminal proBNP) can predict cardiovascular complications in noncardiac surgery.. The authors undertook a systematic review and individual patient data meta-analysis to determine whether postoperative BNPs predict postoperative cardiovascular complications at 30 and 180 days or more.. The authors identified 18 eligible studies (n = 2,051). For the primary outcome of 30-day mortality or nonfatal myocardial infarction, BNP of 245 pg/ml had an area under the curve of 0.71 (95% CI, 0.64-0.78), and N-terminal proBNP of 718 pg/ml had an area under the curve of 0.80 (95% CI, 0.77-0.84). These thresholds independently predicted 30-day mortality or nonfatal myocardial infarction (adjusted odds ratio [AOR] 4.5; 95% CI, 2.74-7.4; P < 0.001), mortality (AOR, 4.2; 95% CI, 2.29-7.69; P < 0.001), cardiac mortality (AOR, 9.4; 95% CI, 0.32-254.34; P < 0.001), and cardiac failure (AOR, 18.5; 95% CI, 4.55-75.29; P < 0.001). For greater than or equal to 180-day outcomes, natriuretic peptides independently predicted mortality or nonfatal myocardial infarction (AOR, 3.3; 95% CI, 2.58-4.3; P < 0.001), mortality (AOR, 2.2; 95% CI, 1.67-86; P < 0.001), cardiac mortality (AOR, 2.1; 95% CI, 0.05-1,385.17; P < 0.001), and cardiac failure (AOR, 3.5; 95% CI, 1.0-9.34; P = 0.022). Patients with BNP values of 0-250, greater than 250-400, and greater than 400 pg/ml suffered the primary outcome at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with N-terminal proBNP values of 0-300, greater than 300-900, and greater than 900 pg/ml suffered the primary outcome at a rate of 1.8, 8.7, and 27%, respectively.. Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery.

Topics: Aged; Aged, 80 and over; Biomarkers; Heart Diseases; Heart Failure; Humans; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Odds Ratio; Postoperative Complications; Postoperative Period; Risk Assessment; Risk Factors; ROC Curve

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

Topics: Aged; Diagnosis, Differential; Disease Progression; Echocardiography; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Male; Myocardial Infarction; Natriuretic Peptide, Brain

Cardiovascular complications, including cardiomegaly, myocardial ischemia and left ventricular hypertrophy, are some of the major determinants of the mortality rate in patients with Cushing's syndrome. We herein report the case of a patient with Cushing's syndrome caused by an adrenal adenoma who presented with congestive heart failure secondary to dilated cardiomyopathy. Follow-up echocardiography showed a marked improvement in the left ventricular cardiac function, and the plasma B-type natriuretic peptide (BNP) levels regressed after successful treatment. "Reversible" dilated cardiomyopathy is rarely associated with Cushing's syndrome; however, it should be recognized. Administering appropriate treatment in a timely manner can reverse this cardiomyopathy along with the other symptoms of Cushing's syndrome.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenalectomy; Aged; Biomarkers; Cardiomyopathy, Dilated; Cardiovascular Agents; Circadian Rhythm; Cushing Syndrome; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Heart Failure; Humans; Hydrocortisone; Natriuretic Peptide, Brain; Remission Induction

Topics: Alternative Splicing; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Designer Drugs; Drug Combinations; Drug Therapy, Combination; Endothelin-1; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Neprilysin; Peptidyl-Dipeptidase A; Protease Inhibitors; Receptors, Angiotensin; Renin-Angiotensin System; Snake Venoms; Tetrazoles; Valsartan

Acute decompensated heart failure (ADHF) is a complex clinical event associated with excess morbidity and mortality. Managing ADHF patients is challenging because of the lack of effective treatments that both reduce symptoms and improve clinical outcomes. Existing guideline recommendations are largely based on expert opinion, but several recently published trials have yielded important data to inform both current clinical practice and future research directions. New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction. Although the largest ADHF trial to date (ASCEND-HF, using nesiritide) was neutral, promising results with other investigational agents have been reported. If these findings are confirmed in phase III trials, novel compounds, such as relaxin, omecamtiv mecarbil, and ularitide, among others, may become therapeutic options. Translation of research findings into quality clinical care can not be overemphasized. Although many gaps in knowledge exist, ongoing studies will address issues around delivery of evidence-based care to achieve the goal of improving the health status and clinical outcomes of patients with ADHF.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cardiotonic Agents; Clinical Trials as Topic; Diet, Sodium-Restricted; Diuretics; Dopamine; Dose-Response Relationship, Drug; Dyspnea; Glycopeptides; Heart Failure; Hemofiltration; Hospitalization; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Peptide Fragments; Prognosis; Protein Precursors; Quality of Health Care; Relaxin; Risk Assessment; Saline Solution, Hypertonic; Urea; Vasodilator Agents; Xanthines

The study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123-labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events.. Although the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database.. Six prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death.. Lethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic-determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001).. Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.

Topics: 3-Iodobenzylguanidine; Aged; Biomarkers; Chi-Square Distribution; Databases as Topic; Disease Progression; Evidence-Based Medicine; Female; Heart; Heart Failure; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Radionuclide Imaging; Radiopharmaceuticals; Risk Factors; ROC Curve; Stroke Volume; Sympathetic Nervous System; Time Factors; Ventricular Function, Left

Biomarkers have an increasingly important clinical role in managing patients with heart failure as well as those with kidney disease, both common conditions with generally poor prognostic outcomes and huge impacts on healthcare economics. For patients with chronic heart failure, biomarkers have become centre place in streamlining diagnostic pathways as well as identifying those with worse prognosis. There is much interest in the role for biomarkers in identifying patients at risk of acute kidney injury, although a number of these currently remain as research tools or are in the early stages of evaluation in clinical practice. Patients with cardiorenal syndrome represent a particular challenge to the clinician, and recent studies have suggested a valuable clinical role for certain biomarkers in this setting, either on their own or in combination. This paper will focus on biomarkers with a current clinical role in patients with cardiorenal disease (natriuretic peptides and neutrophil gelatinase-associated lipocalin), although brief reference will be made to other biomarkers with potential future application.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Biomarkers; Cardio-Renal Syndrome; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Failure, Chronic; Lipocalin-2; Lipocalins; Natriuretic Peptide, Brain; Natriuretic Peptides; Nursing Diagnosis; Peptide Fragments; Prognosis; Proto-Oncogene Proteins

Systolic dysfunction, clinical heart failure and elevated levels of neurohormonal peptides are major predictors of adverse outcome after acute myocardial infarction (MI). In the present thesis we evaluated global longitudinal strain (GLS) in patients with acute MI in relation to neurohormonal activation, in-hospital heart failure and prognosis with specific attention to the group of patients with preserved LVEF that currently do not meet the criteria for anti remodeling therapies.. GLS was found to be significantly associated with neurohormonal activation as assessed by NT-proBNP levels and that this association was present also in patients with preserved LVEF. Patients with clinical HF during hospitalization for acute MI had significantly poorer GLS compared to controls and this relationship was robust when adjusting for known factors associated with elevated LV filling pressure such as left atrial volume and E/e' ratio. Furthermore, measurement of GLS attenuated the value of NT-proBNP in relation to in-hospital HF in patients with preserved LVEF. Finally, GLS was related to outcome in the largest ever echocardiographic deformation study of patients with acute MI and relatively preserved LVEF. We found that GLS predicted mortality and heart failure admissions and that the effect on mortality was driven by a significantly increased risk of cardiac death in patients with impaired GLS.. In conclusion, the results of this thesis demonstrate that GLS as a measure of LV systolic function is significantly related to elevated neurohormonal activation, early hemodynamic deterioration and predict adverse outcome in a low risk population without indications for anti remodeling therapies. Early measurement of GLS in this population could be used as a risk stratification tool for added monitoring and clinical trials.

Topics: Electrocardiography; Heart Failure; Heart Ventricles; Humans; Myocardial Infarction; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

The cardiac hormone, B-type natriuretic peptide (BNP), is one of human natriuretic peptides which possesses cardiorenal protective actions and is used as a therapeutic and a biomarker for heart failure (HF). Its prohormone, proBNP1_108, is processed by the proNPs convertases, corin or furin, to inactive NT-proBNP1_76 and active BNP1-32. Paradoxically, circulating NT-proBNP and BNP are elevated in HF leading to the use of BNP as a sensitive and predictive marker of HF. This paradox may be explained by the "nonspecific" nature of conventional assays and/or a relative deficiency state of "active BNP" as characterized by an increase in inactive proBNP_108 and a decrease in active BNP1-32. Therefore, understanding the regulation of proBNP1_108 processing and the role of the convertase corin may be important in understanding the physiology of HF. Corin is expressed in heart and kidney and may play an important role in regulating blood pressure and remodeling of the heart. The processing of proBNP1_108 by corin may be controlled by O-linked glycosylation of proBNP1-108. A potential impairment of proBNP1lo8 processing in HF may be linked to dysregulation of the convertase corin, which may offer therapeutic opportunities to control proBNPlo0s processing and its activation in HF.

Topics: Amino Acid Sequence; Animals; Biomarkers; Glycosylation; Heart; Heart Failure; Humans; Molecular Sequence Data; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Serine Endopeptidases

Natriuretic peptides (NPs) are entered in current guidelines for heart failure (HF) diagnosis and management because of their high specificity and sensibility in screening patients with acute dyspnea. Due to their availability and relatively low cost, they became the first step examinations in HF patients evaluation at hospital admission together with clinical and chest radiography examination. NPs are released following any cardiac haemodynamic stress due to volume or pressure overload and should be considered as a mirror of cardiac condition helping in recognizing patients with poor outcome. Moreover, the exact role of NPs in early HF stages, in isolated diastolic dysfunction, and in general population is questioned. Several promising reports described their potential role; however, the wide cut-off definition, inclusion criteria, and intrinsic measurement biases do not actually consent to their clinical application in these settings. A multimodality strategy including both NPs and imaging studies appears to be the best strategy to define the cardiac dysfunction etiology and its severity as well as to identify patients with higher risk. In this review, we describe the current and potential role of NPs in patients with asymptomatic cardiac insufficiency, evaluating the requirement to obtain a better standardization for imaging as for laboratory criteria.

Topics: Artifacts; Biomarkers; Clinical Trials as Topic; Comorbidity; Diastole; Dyspnea; Emergency Service, Hospital; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Reference Standards; Risk Assessment; Sensitivity and Specificity; Sodium Potassium Chloride Symporter Inhibitors; Ventricular Dysfunction, Left

B-type natriuretic peptide (BNP) is a member of a fournatriuretic peptide family that shares a common 17-peptide ring structure. The N-terminal fragment (NT-pro-BNP) is biologically inert, but both are secreted in the plasma in equimolar quantities and both have been evaluated for use in the management of congestive heart failure. BNP and NT-pro-BNP are frequently used in the diagnosis of congestive heart failure and distinguishing between patients with dyspnoea of cardiac or pulmonary origin. Values of NT-pro-BNP are affected by age or the presence of one or several co-morbidities such as chronic renal failure, type 2 diabetes, and acute coronary syndrome. 'Normal' values of these peptides also vary depending on the type of test used. The performance characteristics of these tests vary depending on the patients on whom they are used and the manufacturer. For this reason, the determination of reference values for this peptide represents such a challenge.

Topics: Age Factors; Biomarkers; Comorbidity; Diagnosis, Differential; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reproducibility of Results; Risk Factors; Severity of Illness Index

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

Heart failure with normal ejection fraction (HFNEF) accounts for approximately 50% of heart failure (HF) cases. To establish the utility of brain natriuretic peptide (BNP) in differentiating HF-related severe dyspnea from non-HF-related acute dyspnea, we used an estimation formula (eF) that was obtained from a series of three meta-regressions. We selected 60 out of 2721 case-control and follow-up studies that were published from 1998 to 2010. The heart failure levels (HFLs) were assessed using the New York Heart Association (NYHA) criteria. Random-effects meta-regression analyses of the natural logarithm (ln) of the BNP odds ratio (OR) were performed on the HFLs. The ln of the median BNP values (lnmBNP) was meta-regressed over the laboratory method (LM). A third meta-regression was performed on the HFLs to account for only the lnmBNP in the homogeneous LM subgroups. To determine the eF, the data from the diseased and control subjects were combined. The Bland-Altman method was used to detect eF bias. The overall BNP(OR) in the subgroup with severe HF was 35. The lnmBNP analysis showed that LM was a significant heterogeneity factor in the meta-regression (slope -0.38; CI -0.59 to -0.16). The meta-regression of lnmBNP on the HFL resulted in the following calculation for eF: estimated HFL (eHFL)=(lnmBNP-3.157)/0.886. The Bland-Altman test revealed no significant difference (0.0997; 95% CI -2.84 to 3.06) between HFL and eHFL. The severe eHFL showed a 78% accuracy. Based on the eF obtained from this meta-analysis, the BNP outcomes were shown to reliably diagnose severe dyspnea in HF and differentiate this condition from non-HF acute dyspnea.

Topics: Case-Control Studies; Dyspnea; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain

Natriuretic peptides are endogenous hormones released by the heart in response to myocardial stretch and overload. While atrial and brain natriuretic peptides (ANP, BNP) were immediately considered cardiac hormones and their role was well-characterized and defined in predicting risk in cardiovascular disease, evidence indicating the role of C-type natriuretic peptide (CNP) in cardiovascular regulation was slow to emerge until about 8 years ago. Since then, considerable literature on CNP and the cardiovascular system has been published; the aim of this review is to examine current literature relating to CNP and cardiovascular disease, in particular its role in heart failure (HF) and myocardial infarction (MI). This review retraces the fundamental steps in research that led understanding the role of CNP in HF and MI; from increased CNP mRNA expression and plasmatic concentrations in humans and in animal models, to detection of CNP expression in cardiomyocytes, to its evaluation in human leukocytes. The traditional view of CNP as an endothelial peptide has been surpassed by the results of many studies published in recent years, and while its physiological role is still under investigation, information is now available regarding its contribution to cardiovascular function. Taken together, these observations suggest that CNP and its specific receptor, NPR-B, can play a very important role in regulating cardiac hypertrophy and remodeling, indicating NPR-B as a new potential drug target for the treatment of cardiovascular disease.

Topics: Cardiovascular Physiological Phenomena; Guanylate Cyclase; Heart Failure; Humans; Molecular Targeted Therapy; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type

Hospitalization for heart failure (HF) is a clinical entity associated with high postdischarge morbidity and mortality, yet few therapies are available to improve outcomes in patients with this condition. In the past decade, large phase III studies of HF treatments have failed to demonstrate drug efficacy, safety, or both, despite encouraging results from preceding phase II trials. This Review is focused on this disconnect between the results of phase II and phase III trials of drugs for HF and discusses findings from five drug-development programs (for levosimendan, tezosentan, tolvaptan, rolofylline, and nesiritide) to shed light on common themes in clinical trials conducted in patients hospitalized for HF. In particular, the importance of selecting the 'right' patient population, drug, and clinical end points to optimize the trial design is discussed. Areas that require further investigation are highlighted and we suggest possible directions that will help to guide future clinical trials in these patients. Large, expensive phase III trials should not be initiated without adequate phase II evidence or on the basis of overly optimistic interpretation of phase II data. Additionally, drug development programs should be targeted not only to change short-term symptoms, but also to improve the postdischarge event rate.

Topics: Animals; Benzazepines; Cardiovascular Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Evidence-Based Medicine; Heart Failure; Humans; Hydrazones; Natriuretic Peptide, Brain; Patient Readmission; Patient Selection; Pyridazines; Pyridines; Risk Assessment; Risk Factors; Simendan; Tetrazoles; Time Factors; Tolvaptan; Treatment Outcome; Xanthines

Mild cognitive impairment among patients with heart failure can be subtle. Heart failure-related variables such as ejection fraction, low systolic blood pressure and functional status are reportedly associated with cognitive impairment among heart failure patients. The purpose of this literature review was to examine the value of cardiac variables commonly assessed during heart failure-related hospitalizations for a phenotypic profile of the risk of cognitive impairment.. A literature review of primary research studies was conducted. Electronic databases (PubMed and CINAHL) were searched using the keywords heart failure, blood pressure, ejection fraction, functional status, and B-type natriuretic peptide (BNP) in combination with the terms cognition, cognitive function, cognitive dysfunction, and cognitive impairment.. Thirty-seven studies met the inclusion criteria. Evidence supports the potential utility of lower ejection fraction, lower blood pressure and functional status and elevated B-type natriuretic peptide as a phenotypic profile for an increased risk of cognitive impairment.. If the risk for cognitive impairment is suspected, specific evaluations of cognition can be performed. For community-dwelling heart failure patients with mild cognitive impairment, more intense interventions to support self-care, increased family involvement and more frequent follow up may be necessary.

Topics: Blood Pressure; Cognitive Dysfunction; Heart Failure; Humans; Natriuretic Peptide, Brain; Phenotype; Self Care; Stroke Volume

To deny the fact that standard HF care has substantial opportunity for improvement is at the peril of even worse outcomes in our patients affected by the disorder. We have presented a strong rationale for the value of BNP- and NTproBNP–guided HF management. Experience gained in biomarker-guided HF trials suggests that the approach results in improvement in the quality of care without an excess of adverse events related to more aggressive management. This alone is difficult to ignore given the gaps in care that exist between RCTs and real-world practice. Beyond this fact, studies examining the strategy of biomarker-guided HF care have shown substantial improvement in outcome compared with well-managed control arms, benefits that are confirmed in meta-analysis and pooled data analyses, and justifies the imminent launch of the pivotal RCT that will lead to more widespread adoption of the approach. Compared with standard management, biomarker-guided care appears cost effective, may improve patient quality of life, and may promote reverse ventricular remodeling. Although certain subgroups such as the elderly may respond in a less vigorous manner to the approach, this may reflect the effects of age on HF therapy and how the strategy is deployed in elders rather than a weakness of the approach in older patients. A fair-minded assessment of the available data suggests that care supported by BNP/NT-proBNP–guided HF treatment—as an adjunct to standard clinical acumen—is superior to standard care. The limitation of standard care strategies is evident from the suboptimal uptake and application of proven therapies documented in HF registries. Far from being a crutch to support what we should already be doing (namely, optimally evaluating and managing our patients solely with clinical means), the inclusion of NP measurement within the HF management strategy augments the quality of monitoring and treatment. Denial of the benefits of NP monitoring potentially retards advances in the care of a high-risk population of patients that continues to grow in size and importance every day.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Left ventricular failure (LVF) is a clinical syndrome caused by abnormal systolic or diastolic function failing to meet the metabolic requirements of the body. It is important to diagnose and manage LVF in the earliest stages to prevent mortality and morbidity. This article extensively reviews the diagnostic, therapeutic, and prognostic utility of natriuretic peptides in LVF.

Topics: Biomarkers; Half-Life; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Pulmonary Embolism; Renal Insufficiency, Chronic; Stroke; Ventricular Dysfunction, Left

Natriuretic peptides are body fluid volume modulators, termed natriuretic peptides due to a role in natriuresis and diuresis. The three mammalian NPs, atrial natriuretic peptide (ANP), brain or b-type natriuretic peptide (BNP) and c-type natriuretic peptide (CNP), have been extensively investigated for their use as therapeutic agents for the treatment of cardiovascular diseases. Although effective, short half-lives and renal side effects limit their use. In approximately 30 years of research, NPs have been discovered in many vertebrates including mammals, amphibians, reptiles and fish, with plants and, more recently, bacteria also being found to possess NPs. Reptiles have produced some of the more interesting NPs, with dendroaspis natriuretic peptide (DNP), which was isolated from the venom of the green mamba (Dendroaspis angusticeps), having greater potency and increased stability as compared to the mammalian family members, and taipan natriuretic peptide c (TNPc), which was isolated from the venom of the inland taipan (Oxyuranus microlepidotus) displaying similar activity to ANP and DNP at rat natriuretic peptide receptor A. Although promising, more research is required in this field to develop therapeutics that overcome receptor-mediated clearance, and potential toxicity issues. This review investigates the use of snake venom NPs as therapeutic drug leads.

Topics: Animals; Atrial Natriuretic Factor; Diuresis; Elapid Venoms; Heart Failure; Humans; Intercellular Signaling Peptides and Proteins; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptides; Receptors, Atrial Natriuretic Factor; Snake Venoms

Topics: Acute Coronary Syndrome; Acute Disease; Atrial Natriuretic Factor; Biomarkers; Critical Care; Dyspnea; Heart Diseases; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Pulmonary Embolism; Reference Values; Risk Assessment

The aim of this review is to analyze in detail some possible pathophysiological mechanisms linking obesity and cardiac endocrine function, in order to try to explain the negative association previously observed between BMI and BNP values in both healthy subjects and patients with cardiovascular diseases. In particular, we discuss the hypothesis that the response of the cardiac endocrine system is the integrated resultant of several and contrasting physiological and pathological interactions, including the effects of peptide and steroid hormones, cytokines, cardiovascular hemodynamics, clinical conditions, and pharmacological treatment. Several studies suggested that gonadal function regulates both body fat distribution and cardiac endocrine function. Visceral fat expansion can increase the clearance of active natriuretic peptides by means of an increased expression of clearance receptors on adipocytes, and in this way, it may contribute to decrease the activity of the cardiac endocrine system. Moreover, obesity is associated with ectopic lipid deposition even in the heart, which may directly exert a lipotoxic effect on the myocardium by secreting in loco several cytokines and adipokines. Obese subjects are frequently treated for hypertension and coronary artery disease. Pharmacological treatment reduces plasma level of cardiac natriuretic peptides, and this effect may explain almost in part the lower BNP levels of some asymptomatic subjects with increased BMI values. At present time, it is not possible to give a unique and definitive answer to the crucial question concerning the inverse relationship between the amount of visceral fat distribution and BNP levels. Our explanation for these unsatisfactory results is that the cardiac endocrine response is always the integrated resultant of several pathophysiological interactions. However, only few variables can be studied together; as a result, it is not possible to perform a complete evaluation of pathophysiological mechanisms under study. We are still not able to well integrate these multiple information together; therefore, we should learn to do it.

Topics: Body Mass Index; Brain-Derived Neurotrophic Factor; Case-Control Studies; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity

Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP.. To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2).. Individual patient meta-analysis.. A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures.. Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change.. Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

Topics: Aged; Analysis of Variance; Biomarkers; Exercise Therapy; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Time Factors; Treatment Outcome

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

In industrialized countries, chronic heart failure (HF) is a major illness and cause of death. However, because of the paucity of specific clinical manifestations of HF, its early diagnosis and management might be challenging. Therefore, biochemical markers of HF are now being closely scrutinized. An ideal biochemical marker should be a prognostic indicator, should assist in the early diagnosis, reflect the therapeutic response, and help grading the risk associated with each stage of HF. This review summarizes our current understanding of biochemical markers of HF.

Topics: Aldosterone; Angiotensins; Biomarkers; Cytokines; Heart Failure; Humans; Natriuretic Peptide, Brain; Neurotransmitter Agents; Prognosis; Renin; Troponin

A unifying hypothesis which satisfactorily explains the clinical syndrome of heart failure has proved elusive. A deeper understanding of the underlying pathophysiology has led to the development of more complex models and, as a result, the evolution of new treatment strategies. In patients undergoing non-cardiac surgery, perioperative heart failure has an incidence of approximately 1% and is a predictor of major adverse cardiovascular events. Although vasodilators undoubtedly play a major role in the management of patients with heart failure, the relative importance of venodilatation remains unclear. The purpose of this article is to discuss the clinical evidence supporting the use of drugs with venodilating properties in surgical patients with heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Hydralazine; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Perioperative Care; Vasodilator Agents

Heart failure is extremely prevalent and is associated with significant mortality, morbidity and cost. Studies have already established mortality benefit with the use of neurohormonal blockade therapy in systolic failure. Unfortunately, physical signs and symptoms of heart failure lack diagnostic sensitivity and specificity, and medication doses proven to improve mortality in clinical trials are often not achieved. Brain natriuretic peptide (BNP) has proven to be of clinical use in the diagnosis and prognosis of heart failure, and recent efforts have been taken to further elucidate its role in guiding heart failure management. Multiple studies have been conducted on outpatient guided management, and although still controversial, there is a trend towards improved outcomes. Inpatient studies are lacking, but preliminary data suggest various BNP cut-off values, as well as percentage changes in BNP, that could be useful in predicting outcomes and improving mortality. In the future, heart failure management will probably involve an algorithm using clinical assessment and a multibiomarker-guided approach.

Topics: Algorithms; Biomarkers; Clinical Trials as Topic; Heart Failure; Humans; Inpatients; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Prognosis; Sensitivity and Specificity

Among the cardiovascular diseases, heart failure (HF) has a high rate of hospitalization, morbidity and mortality, consuming vast resources of the public health system in Brazil and other countries. The correct determination of the filling pressures of the left ventricle by noninvasive or invasive assessment is critical to the proper treatment of patients with decompensated chronic HF, considering that congestion is the main determinant of symptoms and hospitalization. Physical examination has shown to be inadequate to predict the hemodynamic pattern. Several studies have suggested that agreement on physical findings by different physicians is small and that, ultimately, adaptive physiological alterations in chronic HF mask important aspects of the physical examination. As the clinical assessment fails to predict hemodynamic aspects and because the use of Swan-Ganz catheter is not routinely recommended for this purpose in patients with HF, noninvasive hemodynamic assessment methods, such as BNP, echocardiography and cardiographic bioimpedance, are being increasingly used. The present study intends to carry out, for the clinician, a review of the role of each of these tools when defining the hemodynamic status of patients with decompensated heart failure, aiming at a more rational and individualized treatment.

Topics: Cardiography, Impedance; Echocardiography; Heart Failure; Hemodynamics; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Physical Examination

Over half of chronic heart failure (CHF) patients are anaemic, and iron deficiency is common. Iron replacement therapy (oral or i.v.) might improve exercise capacity and quality of life (QOL).. We carried out a systematic review and meta-analysis of all randomized control trials that compared iron with no therapy for CHF patients with iron deficiency, whether or not they were anaemic. We searched electronic databases as well as haematology and cardiology conferences up to August 2011. The primary outcome was the effect of iron on QOL parameters such as New York Heart Association (NYHA) class and the Minnesota Living With Heart Failure Questionnaire (MLHWFQ). Secondary outcomes included all-cause mortality, mean ejection fraction, 6 min walk distance (6MWD), hospitalizations due to any cause, iron indices, C-reactive protein levels, and adverse events. Four trials performed fulfilled the inclusion criteria. A total of 370 patients were treated with i.v. iron, compared with 224 control patients. There was significant improvement in QOL in the iron arm according to the MLWHFQ score at 26 weeks, with a weighted mean difference of -18.00 (-22.54, -13.46, I(2) = 0%]. The point estimate for improvement in NYHA class was in favour of iron. Iron reduced the number of hospitalizations and C-reactive protein levels, and increased the 6MWD and mean ejection fraction. Iron indices were significantly improved without a change in haemoglobin levels. No increase in the rate of adverse events was found.. Intravenous iron therapy is associated with improved QOL parameters, reduction in hospitalizations, and increased 6MWD. Treatment with i.v. iron is safe, with no increased rate of adverse events. The results of our analysis are limited by the paucity of trials, and significant heterogeneity between trials.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Chi-Square Distribution; Confidence Intervals; Dietary Supplements; Exercise Tolerance; Health Status Indicators; Heart Failure; Humans; Infusions, Intravenous; Iron, Dietary; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Surveys and Questionnaires

Cardiac biomarkers in intensive care medicine are an excellent complement to existing clinical and diagnostic information in specific diseases. Due to their lack of specificity, the diagnostic properties of common cardiac biomarkers, such as natriuretic peptides and cardiac troponins, remain ambiguous, while their prognostic value has already been proven. In addition, there are several promising new biomarkers that might contribute to a "multimarker strategy" in the critically ill patient in the future, but further evaluation is still required.

Topics: Biomarkers; Creatine Kinase, MB Form; Critical Illness; Heart Failure; Humans; Intensive Care Units; Myocardial Ischemia; Natriuretic Peptide, Brain; Natriuretic Peptides; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Edema; Pulmonary Embolism; Sensitivity and Specificity; Shock, Cardiogenic; Troponin; Troponin C

The cardio-renal syndromes (CRS) are the result of complex bidirectional organ cross-talk between the heart and kidney, with tremendous overlap of diseases such as coronary heart disease, heart failure (HF), and renal dysfunction in the same patient. Volume overload plays an important role in the pathophysiology of CRS. The appropriate treatment of overhydration, particularly in HF and in chronic kidney disease, has been associated with improved outcomes and blood pressure control. Clinical examination alone is often insufficient for accurate assessment of volume status because significant volume overload can exist even in the absence of peripheral or pulmonary edema on physical examination or radiography. Bioelectrical impedance techniques increasingly are being used in the management of patients with HF and those on chronic dialysis. These methods provide more objective estimates of volume status in such patients. Used in conjunction with standard clinical assessment and biomarkers such as the natriuretic peptides, bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration therapies and subsequently restoring such patients to a euvolemic or optivolemic state. In this article, we review the use of these techniques in CRS.

Topics: Acute Disease; Biomarkers; Blood Volume; Body Composition; Cardio-Renal Syndrome; Dielectric Spectroscopy; Electric Impedance; Heart Failure; Hemofiltration; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Water-Electrolyte Imbalance

The care of patients with heart failure can be challenging, with few objective tools available to assist in therapy decision-making. Natriuretic peptides are powerfully prognostic biomarkers in patients with heart failure and may represent an objective target for therapy. Accordingly, the use of biomarker-guided care with either B-type natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has been recently explored. Over the past few years, a number of studies with heterogeneous inclusion criteria, methods and results have been performed. We have reviewed the available literature, summarizing the results of biomarker-guided heart failure trials and deriving recommendations for optimal application of biomarker-guided heart failure care based on the experience gained. In general, positive studies had low BNP or NT-proBNP target concentrations (∼100 pg/mL and ∼1000 pg/mL, respectively) and achieved lower natriuretic peptide concentrations compared with standard care. Patients in the biomarker-guided arms of the studies typically received more aggressive heart failure care and had no excess adverse outcomes. In the recent ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study, patients treated with biomarker-guided care also had improved quality of life and significantly better reverse remodeling on echocardiography compared with patients who received standard care. In conclusion, heart failure therapy guided by a goal to reduce natriuretic peptide concentrations below prognostically-meaningful levels results in more aggressive heart failure care, is well tolerated and is associated with superior outcomes.

Topics: Biomarkers; Disease Management; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Protein Precursors

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

Heart failure (HF) prevention is an indisputably laudable goal, albeit with undefined global public health impact in an increasingly elderly population with competing cardiovascular and noncardiovascular risks for morbidity and mortality. The understanding of cardiac and noncardiac structural and functional abnormalities that predispose to the diverse clinical HF syndrome is rapidly advancing, and novel approaches for prevention and treatment are needed. Successful approaches mandate not only identification of discrete therapeutic targets but also research into the developing sciences of health care delivery and behavioral modification. Targeting Stage B HF represents one such potential strategy.

Topics: Asymptomatic Diseases; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Prevalence; Risk Assessment; Ventricular Dysfunction, Left

Acute myocarditis is an inflammatory disease of the heart muscle that may progress to dilated cardiomyopathy and chronic heart failure. A number of factors including the sex hormone testosterone, components of innate immunity, and profibrotic cytokines have been identified in animal models as important pathogenic mechanisms that increase inflammation and susceptibility to chronic dilated cardiomyopathy. The clinical presentation of acute myocarditis is non-specific and mimics more common causes of heart failure and arrhythmias. Suspected myocarditis is currently confirmed using advanced non-invasive imaging and histopathologic examination of heart tissue. However, the diverse presentations of myocarditis and the lack of widely available, safe, and accurate non-invasive diagnostic tests remain major obstacles to early diagnosis and population based research. Recent advances in the understanding of disease pathogenesis described in this review should lead to more accurate diagnostic algorithms and non-invasive tests.

Topics: Algorithms; Animals; Biomarkers; Biopsy; Cardiomyopathy, Dilated; Diagnosis, Differential; Disease Progression; Early Diagnosis; Evidence-Based Medicine; Heart Failure; Humans; Inflammation; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Sex Distribution; Troponin I; Troponin T

Hospitalization for decompensated heart failure (HF) is associated with extraordinarily high rates of morbidity and mortality. Despite its high prevalence its pathophysiologic mechanisms and future risk stratification remain poorly defined and understudied. Several clinical Risk Scores to recognize high risk patients, has been purposed in the past but they are not able to completely identify future adverse events. In this sense, laboratory biomarkers play an important role in heart failure, but there remain unanswered questions regarding optimization of their use. One of the biggest hopes for utilizing biomarker testing is to determine the level of disease severity in a manner to triage medical decisions as well as to monitor their responses. Early diagnosis is very important for a better therapy optimization and outcome improving. Indeed, identification is often difficult because of symptoms unspecificity and the lack of gold standard protocol to make diagnosis. B-type natriuretic peptide is a useful tool to confirm or rule out heart failure. Therefore, BNP is one of the most best prognostic indicator in all stages of heart failure predicting outcome in both hospitalized and outpatients. Other neurohormonal, inflammatory and metabolic markers may add complementary information to that provided by currently available B-type natriuretic peptide assays. However all specific and general laboratory parameters cannot substitute to traditional clinical evaluation but could be used in adjunction for more precise evaluation and assessment. We reviewed traditional and some of emerging biomarkers of potential clinical application in HF setting.

Topics: Algorithms; Biomarkers; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Neurotransmitter Agents; Stress, Physiological

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

Brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) are important biomarkers for pediatric cardiovascular diseases. Peptide levels are associated with age and gender. Current studies have shown that BNP and NT-proBNP are valuable in the diagnosis of heart failure, with a high specificity and sensitivity. They also contribute to differentiating heart failure from acute respiratory distress induced by simple pulmonary factors. In addition, BNP and NT-proBNP are useful in the evaluation of disease severity and treatment guidance in children with pulmonary hypertension, cardiomyopathy and Kawasaki disease. Current limitations include the relatively small sample size of the study, the detection method and a range of normal values that are not completely uniform.

Topics: Cardiomyopathies; Cardiovascular Diseases; Child; Dyspnea; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV afterload and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

Topics: Exercise Tolerance; Health Status Indicators; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Oxygen Consumption; Ultrasonography; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

Pulmonary hypertension (PH) is characterized hemodynamically by significantly elevated pulmonary artery pressure, which if sustained can result in clinical deterioration due to progressive right-sided heart failure and death. Establishing the etiology of PH in a patient before treatment is imperative. Effective evidence-based therapeutic agents for treating PH have been developed. However, appropriately powered, randomized trials in PH associated with left-sided heart failure are sparse, and those that have been performed have shown no benefit or harm. An improved understanding of the pathophysiology, definition, and development of new therapies for treating PH associated with left-sided heart failure is urgently needed.

Topics: Calcium Channel Blockers; Endothelins; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Agents; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Prognosis; Stroke Volume; Ventricular Function, Left

Since the initial studies showing the usefulness of B-type natriuretic peptide for aiding in heart failure diagnosis, a vast number of other clinical applications for this neurohormone have emerged. In addition to refining our capabilities to diagnose and prognosticate in acute heart failure, natriuretic peptides are now being used in outpatient heart failure clinics, in screening programs, and in risk prediction algorithms in various settings. In just 10 years, B-type natriuretic peptide has gone from being an unknown biomarker to being one of the most useful in cardiology and beyond. In this perspective piece, the investigators review what we have learned about using natriuretic peptides over the past 10 years and the anticipated advances in their use over the next decade.

Topics: Acute Disease; Aftercare; Biomarkers; Cardio-Renal Syndrome; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment

This review provides the rationale for integrating genomic and protein biomarkers in the evolving diagnosis and management of dilated cardiomyopathy (DCM) and its causal pathway to heart failure (HF), with a larger objective to serve as a template for genomic and phenomic profiling of other cardiovascular disease. DCM is a major cause of HF and accounts for more than half of heart transplantation in adults and children worldwide. DCM may remain asymptomatic for years, but HF and/or arrhythmias, both late manifestations of the disease, ultimately cause significant morbidity and mortality. A significant proportion of DCM has a genetic etiology. DCM can also result from environmental injury such as infection, toxins, or catecholamine excess. While molecular genetic testing can identify those at risk for genetic DCM, epigenetic and sentinel phenomic staging can help to identify those at highest risk in need for intervention. Phenomic staging includes integrating clinical and imaging features, transcriptomics, higher order proteomics and metabolomics interactions, and epidemiological data. This principle can be applied in family members of patients with DCM, where genetic testing and clinical phenotyping are indicated. This will allow the design of specific interventions tailored to individuals sharing similar risks, to alter the natural history of DCM and obviate complications such as HF/arrhythmias.

Topics: Adult; Animals; Biomarkers; Cardiomyopathy, Dilated; Disease Progression; Epigenomics; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Matrix Metalloproteinases; Mice; Natriuretic Peptide, Brain; Precision Medicine; Proteomics; Receptors, Cell Surface; Risk Assessment

Acute heart failure is one of the most common condition leading to hospital admission and is burdened by important mortality and readmission rates. A timely diagnosis of congestive heart failure at admission by hospitalists is essential for an early and tailored medical management. The initial clinical evaluation based on symptoms, physical signs and chest radiography remains inconclusive for the diagnosis in many patients with acute dyspnea, and the use of natriuretic peptide testing (BNP and NT-proBNP) through a two cut-point strategy is currently recommended as first-line diagnostic complement in the acute care setting. Bedside Doppler echocardiography is another reliable, noninvasive method that offers additional diagnostic information over the initial clinical evaluation. Along with echocardiographic evidence of depressed left ventricular systolic function, several simple Doppler indexes have been validated in the emergency diagnosis of congestive heart failure. Doppler echocardiography at bedside may especially benefit to patients with intermediate, inconclusive natriuretic peptide concentrations. The aim of the present review was to offer to the hospitalist a practical overview on the relative contribution of natriuretic peptide testing and bedside Doppler echocardiography to the diagnosis of acute heart failure in the emergency care setting.

Topics: Acute Disease; Biomarkers; Early Diagnosis; Echocardiography, Doppler; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; Sensitivity and Specificity; Treatment Outcome

Effective management of patients with pulmonary arterial hypertension (PAH) requires comprehensive prognostic evaluation in order to determine optimal management strategies. Although a number of clinical and hemodynamic parameters linked to PAH prognosis have been identified, some are associated with significant limitations (eg, invasive techniques, subjective measures). There is a need for noninvasive and objective measures to be established that function as biomarkers for the diagnosis and assessment of disease prognosis, and that determine response to therapy in patients with PAH. Reflecting the highly complex etiology of the disease, a large number of potential biomarkers have been, and continue to be, investigated in PAH, including those reflecting right heart function, endothelial dysfunction, and markers of inflammation and second organ failure. However, it has become clear that scientifically interesting biomarkers may not necessarily be clinically useful. Of the range of biomarkers investigated in PAH to date, only brain natriuretic peptide and its N-terminal cleavage product have been included as prognostic parameters in treatment guidelines. It is unlikely that any single biomarker will provide all the relevant information required for an individual patient, and the potential for combining markers is currently of considerable interest. Future studies are required to determine the optimal combination of existing and emerging biomarkers in the clinical setting.

Topics: Biomarkers; Creatinine; Endothelium, Vascular; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Inflammation; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prognosis; Sodium; Troponin T

Among patients with heart failure, concentrations of natriuretic peptides are strongly linked to the presence and severity of structural heart disease and are strongly prognostic in this setting. Additionally, favorable reduction in the concentration of either B-type natriuretic peptide (BNP) or B-type natriuretic peptide and its amino-terminal cleavage fragment (NT-proBNP) may be seen during treatment of heart failure, with parallel improvement in prognosis. This has led to the hypothesis that intensified treatment directed at reducing natriuretic peptide concentrations may improve outcomes in heart failure.. In chronic heart failure, studies suggest that a strategy of standard-of-care management together with a goal to suppress BNP or NT-proBNP concentrations leads to greater application of guideline-derived medical therapy and is well tolerated. In certain studies of this BNP or NT-proBNP 'guided' approach, patients treated with biomarker-guided care had superior outcomes when compared with standard heart failure management alone, particularly in younger study populations, in patients with left ventricular systolic dysfunction, and particularly when substantial reductions in natriuretic peptides were achieved in association with biomarker-guided care.. Natriuretic peptide 'guided' management appears promising in patients suffering from chronic heart failure. Large-scale pivotal trials to confirm the approach are planned.

Topics: Biomarkers, Pharmacological; Heart Failure; Humans; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Recent studies reported that many different biochemical forms of B-type-related peptides circulate in human blood. In particular, a significant amount of the prohormone peptide (i.e., proBNP108) can be detected in plasma of patients with heart failure. These data indicate that the posttranslational maturation processing of the B-type natriuretic peptide (BNP) precursor may not be efficient in heart failure. The aim of this chapter is to describe the biochemical pathways of proBNP108 maturation and to discuss the pathophysiological relevance of alteration of the posttranslational maturation mechanisms in heart failure. An impaired cardiac endocrine function was proposed to explain the altered electrolyte and fluid homeostasis occurring in chronic heart failure. Recent studies demonstrated that a great part of BNPs assayed by immunoassay methods in healthy subjects and in patients with cardiovascular disease is devoid of biological activity. These findings suggest that an alteration in posttranslational maturation of BNP precursor may promote the resistance to biological action of BNP in patients with heart failure at a prereceptor level. These studies also open a new and more complex scenario regarding the circulating BNPs. The active hormone (i.e., BNP1-32) may be produced even in vivo from the circulating precursor proBNP108 by plasma enzyme degradation, such as the soluble form of corin, possibly able to process the circulating intact precursor of natriuretic hormones. As a future perspective, the simultaneous measurement of the proBNP1-108 and the active peptide BNP1-32 with more specific methods could allow a more accurate estimation of both production/secretion of B-type-related peptides from cardiomyocytes and the true activity of the cardiac endocrine function.

Topics: Animals; Heart; Heart Failure; Humans; Immunoassay; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Processing, Post-Translational

B-type natriuretic peptide or brain natriuretic peptide (BNP) is a cardiac peptide hormone. The principal stimulus for BNP synthesis is myocyte stretch. BNP binds to the natriuretic peptide receptor-A causing increased intracellular cyclic guanosine monophosphate (cGMP) production and shows cardio- and renoprotective effects. However, high endogenous BNP levels are associated with a lack of effect in severe heart failure. Moreover, in experimental heart failure, the response to treatments targeting the natriuretic peptide system is attenuated. This article reviews potential mechanisms that may explain the 'BNP paradox' in heart failure with a focus on interspecies differences, on known and presumed specificities of canine BNP biology, and on experimental studies in dogs. Resistance to BNP is far from fully understood but may be due to post-translational modifications and alteration in proBNP processing, receptor downregulation and desensitization, blunted intracellular signalling and increased clearance of BNP(1-32.) Alternatively, resistance to BNP may be due to BNP(1-32) shortening into additional truncated forms that are less biologically effective. Future improvement in understanding of BNP biology may provide the rationale for innovative therapeutic strategies to maximize cardiovascular and renal cGMP bioavailability.

Topics: Animals; Dog Diseases; Dogs; Heart Failure; Natriuretic Peptide, Brain; Species Specificity

The discovery of cardiac hormone production significantly changed the evaluation of the function of the heart, which is rather regarded as a determining factor of the electrolyte and hemodynamic homeostasis cooperating with other organ systems instead of a mechanical pump. The most important hormones produced by the heart are the natriuretic peptides that have the primary role of protection against volume overload through natriuretic, diuretic, vasodilator and antiproliferative effects. They are integrative markers of the cardiac, vascular and renal functions and marking cardiorenal distress. Brain natriuretic peptide and the N-terminal pro-hormone (NT-proBNP) became generally accepted markers of heart failure exceeding traditional pathophysiological significance of those. They are useful in the diagnosis, estimation of prognosis and therapy guidance and their therapeutic administration is also available. Although the detection of extraadrenal aldosterone production is an exciting new discovery, intracardial aldosterone production is not significant in human beings. The intracardial thyroid hormone production is regulated by deiodinase activity. The role of elevated T3 concentration was suggested in the development of cardiac hypertrophy, while low T3 is assumed to be important in adaptation to hypoxia. An unexpected, complex relation can be determined between epicardial adipose tissue and coronary artery diseases, cytokine and adipokine production of adipocytes might be a part of the self-enhancing process of atherosclerosis.

Topics: Adipocytes; Adipokines; Aldosterone; Biomarkers; Cardiomegaly; Coronary Artery Disease; Cytokines; Heart Failure; Humans; Intra-Abdominal Fat; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Pericardium; Triiodothyronine

The aim of the study was to assess the usefulness of systematic natriuretic peptide testing in the management of patients presenting with acute dyspnea to emergency departments (EDs).. We performed a systematic review and meta-analysis of randomized controlled trials assessing the usefulness of B-type natriuretic peptide (BNP) or its N-terminal fragment (NT-proBNP) in the management of patients presenting with dyspnea into ED. We searched Medline, Embase, and conference proceedings without restriction on neither language nor publication year. Selection of studies, data collection, and assessment of risk of bias were performed by 2 reviewers independently and in duplicate. Outcomes included hospital admission rate, time to discharge, and length of hospital stay, mortality and rehospitalization rates, and total direct medical costs. Combined risk ratios were estimated using fixed or random effects model. Duration and cost data were not combined.. Four randomized controlled trials, representing 2041 patients, were selected. In 4 trials, there was a tendency for hospital admission to be reduced in the intervention group (combined risk ratio, 0.95; 95% confidence interval, 0.89-1.01). Time to discharge was significantly reduced in 2 trials, whereas there was no significant reduction in hospital length of stay in 3 trials. There was no significant effect on in-hospital and 30-day mortality rates or rehospitalization rates (3 trials reporting each outcome). Two trials found significant reduction in direct costs.. The current evidence remains inconclusive on whether systematic natriuretic peptide testing is useful for the management of patients presenting to ED with acute dyspnea.

Topics: Aged; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments

Tremendous advances have been made in understanding the pathophysiology and treatment of congestive heart failure (CHF). However, diagnosis still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are non-specific and poorly sensitive indicators for early CHF that can be largely undetected. The discovery of natriuretic peptides (BNP) as diagnostic biomarkers has been one of the most critical advances for heart failure diagnosis. Therefore, both B-type and N-terminal pro-B-type have potential role in the diagnosis of heart failure, as well as in prognostic risk assessment. A single determination of BNP at any time during the progression of chronic HF provides a clinically useful tool for risk stratification. The hypothesis that repeated measurements might carry prognostic information beyond a single measure was confirmed in different settings. One of the main interests is given to the values of repeated determinations for monitoring progression of disease, and for the evaluation of the clinical effects of medical therapy. Nevertheless, despite thousands of papers describing their potential utility, current guidelines have not endorsed the highest level of recommendation for their use, in part, because the application in clinical practice is often limited for the absence of well codified cut off. Recently, European guidelines emphasized the role of natriuretic peptides as potential laboratory markers. In the near future, algorithm building will take into consideration clinical and echocardiographic parameters as well as NP measurements, and this may lead to a correct diagnosis and identification of patients at high risk. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in heart failure and coronary disease.

Topics: Biomarkers; Coronary Artery Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides

Whereas the role of the cardiac natriuretic peptides, ANP and BNP, in some aspects of physiology and pathophysiology is clear, their potential in diagnosis, prognosis, and therapeutics in many clinical disorders remains uncertain. We predict that circulating levels of these peptides will find increasing diagnostic utility in patients presenting with dyspnoea, in guiding the complex pharmacotherapy in heart failure, and may likewise be useful in guiding the management of patients on chronic maintenance renal dialysis. We predict also that levels of these peptides will be of practical use as prognostic indicators in 'at-risk' populations (such as those with diabetes, coronary heart disease, hypertension, thalassaemia, etc.) but probably not in the general population. It appears likely that administration of these peptides will find a place in the therapeutics of acute myocardial infarction, but this is less clear for heart failure. We describe the presence of a segment of the signal peptide for BNP within the circulation and discuss its potential clinical utility.

Topics: Animals; Atrial Natriuretic Factor; Dyspnea; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Increased brain natriuretic peptide (BNP), reflecting increased ventricular wall stress and pressure, is a well-known diagnostic and prognostic marker in patients with chronic heart failure. Heart transplantation (HT), the process of replacing the failing heart and restoring haemodynamics, should normalize cardiac endocrine function. Nevertheless, BNP levels remain raised after HT, likely because of increased secretion and/or decreased clearance of the cardiac hormone. Thus, BNP increases in proportion to the extent of left and right ventricular dysfunction after HT. Clinically complicated cardiac transplantation (cardiac systolic dysfunction, renal failure) is associated with the higher level of circulating BNP, and clinically successful cardiac transplantation (mild cardiac diastolic dysfunction) is associated with moderately increased BNP values. Surprisingly, however, increased BNP has also been found after HT in the absence of haemodynamic perturbations or allograft rejection, raising the hypothesis that even subtle modification in the immune system might influence BNP expression. In view of the potential interest in the cardiac hormone for subjects' risk stratification and therapy, a better knowledge of the mechanisms involved in the BNP increase after HT might be helpful for HT recipients' follow-up.

Topics: Animals; Biomarkers; Heart Failure; Heart Transplantation; Humans; Inflammation Mediators; Natriuretic Peptide, Brain; Treatment Outcome; Up-Regulation

The natriuretic peptides (NPs) are a group of structurally similar yet genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. Since the discovery of atrial natriuretic peptide in 1981, the diagnostic, prognostic, and therapeutic significance of NPs have been studied extensively in relation to heart failure. Indeed, it now is understood that a hallmark of heart failure is the activation of the cardiac endocrine system, in particular the natriuretic peptide family including atrial natriuretic peptide and B-type natriuretic peptide. Currently, the only approved therapeutic application for NPs is the intravenous treatment of acute decompensated heart failure. However, in recent years there has been considerable research aimed at creating novel NPs and administering them via novel routes. This review focuses on the novel NPs that have been created and on novel approaches for their administration.

Topics: Administration, Oral; Alternative Splicing; Atrial Natriuretic Factor; Cardiovascular Agents; Drug Design; Heart Failure; Humans; Injections, Subcutaneous; Natriuretic Peptide, Brain; Natriuretic Peptides; Treatment Outcome

Drug therapies for patients with acute heart failure syndromes (AHFS) are reviewed, including clinical practice guideline recommendations for the treatment of hospitalized patients with heart failure (HF).. AHFS may be defined as new-onset, gradual, or rapidly worsening HF signs and symptoms that require urgent therapy. Clinical practice guidelines from the American College of Cardiology Foundation-American Heart Association, Heart Failure Society of America, and European Society of Cardiology offer recommendations for the management of AHFS, addressing the role of diuretics, vasodilators, and inotropes. The guidelines emphasize the utility of vasodilators for patients with signs and symptoms of pulmonary congestion, including pulmonary edema or severe hypertension or both, who have not responded to diuretics. The early initiation of vasoactive medications, including diuretics and vasodilators, has been linked to improved outcomes in some reports. Conversely, the use of inotropes is de-emphasized, particularly as part of the routine management of these patients. Newer agents, including vasopressin antagonists, have also been approved recently but are not addressed by the clinical practice guidelines. The guidelines address the importance of initiating and optimizing evidence-based oral medications for long-term use, including angiotensin-converting-enzyme (ACE) inhibitors, angiotensin-receptor blockers, β-blockers, and aldosterone antagonists, during the patient's hospital stay in an effort to address long-term outcomes.. Drug therapy of AHFS may include diuretics, vasodilators, morphine, ACE inhibitors, digoxin, inotropes, and vasopressin antagonists. Clinical practice guidelines for patients with AHFS provide a useful mechanism to incorporate available evidence and standards of practice into patient care.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Dobutamine; Heart Failure; Humans; Milrinone; Morphine; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Practice Guidelines as Topic; Vasodilator Agents

Myocardial fibrosis, progressive over-accumulation of extracellular matrix (ECM) components in cardiac muscle, defined as a key component of heart failure and since then various studies showed a strong connection between fibrosis and progression of heart failure. The impaired left ventricular diastolic and systolic functions that are originated by fibrosis are used to predict poor clinical outcome in dilated cardiomyopathy. Even though endomyocardial biopsy is still considered as a gold standard, various noninvasive imaging techniques have been used to detect presence, location and extend of myocardial fibrosis. Cardiac magnetic resonance emerged as a crucial noninvasive imagining technique because of its high accuracy and high fidelity in detection of fibrosis. The noninvasive assessment of fibrosis is advantageous in early prediction of possible adverse outcomes and creates an opportunity to utilize new therapeutic approaches that target fibrosis in heart failure.

Topics: Endomyocardial Fibrosis; Heart Failure; Heart Failure, Diastolic; Humans; Magnetic Resonance Imaging; Myocardium; Natriuretic Peptide, Brain; Prognosis; Ventricular Remodeling

The diagnosis of heart failure is essentially based upon the presence of typical symptoms and signs of congestion or a low cardiac output as well as the objective evidence of cardiac dysfunction. Basic tests include clinical examination, ECG, and chest x-ray. However, findings from these tests are neither absolutely specific nor sensitive for a diagnosis of heart failure. A low B-type natriuretic peptide concentration in a patient with acute dyspnoea makes the diagnosis of heart failure as the cause of a patient's symptoms unlikely. If HF is not unlikely based on ECG, x-ray, and BNP, an echocardiogram is recommended. Echocardiography is the single most useful tests to detect cardiac dysfunction and to identify the exact mechanism underlying the patient's symptoms of heart failure, which is essential to establish an appropriate treatment plan.

Topics: Algorithms; Coronary Angiography; Echocardiography; Electrocardiography; Heart Failure; Hemodynamics; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Predictive Value of Tests; Tomography, X-Ray Computed

We sought to determine prospectively whether serial assessment of the natriuretic peptide prohormone, amino-terminal pro-B-type natriuretic peptide (NT-pro-BNP), correlated with clinical severity and outcomes in children hospitalized for acute decompensated heart failure (ADHF). Patients (>1 month of age) admitted from 2005 to 2007 with ADHF requiring intravenous vasoactive/diuretic therapy for ADHF were eligible. Serum NT-pro-BNP levels were obtained within 24 hours of admission and at prespecified intervals, and clinical caregivers were blinded to these levels. End points included hospital discharge, death or cardiac transplantation, and care escalation including the need for mechanical circulatory support (MCS) was noted. Twenty-four patients were enrolled: 22 survived to hospital discharge and 2 died. Ten required MCS (of which 6 underwent cardiac transplantation). Two patients underwent transplantation without MCS. For the entire cohort, NT-pro-BNP levels peaked at days 2 to 3 after admission, with a subsequent gradual decrease until discharge. However, for those who did require MCS, NT-pro-BNP failed to decrease consistently until after MCS initiation. At discharge, NT-pro-BNP levels were significantly decreased from admission levels but remained well above normal for all patients. Single-point NT-pro-BNP levels on admission did not correlate with independently assessed clinical scores of heart failure severity or predict the need for MCS in this cohort. In conclusion, serial NT-pro-BNP levels demonstrated an incremental trend after 48 hours in patients who went on to require MCS but decreased in all other patients and may therefore assist the decision to initiate or avoid MCS after admission for pediatric ADHF.

Topics: Acute Disease; Biomarkers; Child; Equipment Design; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Gene Expression; Gene Expression Regulation; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptide Fragments; Tissue Distribution; Transcription, Genetic

Whether additional benefit can be achieved with the use of statin treatment in patients with chronic heart failure (CHF) remains undetermined.. Statin treatment may be effective in improving cardiac function and ameliorating ventricular remodeling in CHF patients.. The PubMed, MEDLINE, EMBASE, and EBM Reviews databases were searched for randomized controlled trials comparing statin treatment with nonstatin treatment in patients with CHF. Two reviews independently assessed studies and extracted data. Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using random effects models.. Eleven trials with 590 patients were included. Pooled analysis showed that statin treatment was associated with a significant increase in left ventricular ejection fraction (WMD: 3.35%, 95% CI: 0.80 to 5.91%, P = 0.01). The beneficial effects of statin treatment were also demonstrated by the reduction of left ventricular end-diastolic diameter (WMD: -3.77 mm, 95% CI: -6.24 to -1.31 mm, P = 0.003), left ventricular end-systolic diameter (WMD: -3.57 mm, 95% CI: -6.37 to -0.76 mm, P = 0.01), B-type natriuretic peptide (WMD: -83.17 pg/mL, 95% CI: -121.29 to -45.05 pg/mL, P < 0.0001), and New York Heart Association functional class (WMD: -0.30, 95% CI: -0.37 to -0.23, P < 0.00001). Meta-regression showed a statistically significant association between left ventricular ejection fraction improvement and follow-up duration (P = 0.03).. The current cumulative evidence suggests that use of statin treatment in CHF patients may result in the improvement of cardiac function and clinical symptoms, as well as the amelioration of left ventricular remodeling.

Topics: Aged; Anticholesteremic Agents; Cholesterol; Cytokines; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Oxidative Stress; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling

Pharmacologic therapy represents the mainstay of treatment for heart failure in children. However, medical therapy for this population is not widely standardized. This is mainly due to the heterogeneity of potential etiologies, the specific challenge of patients with univentricular physiology and the lack of evidence-based prospective randomized clinical trials in pediatric patients. In fact, most current strategies are based largely on extrapolated data from adult studies. Although the classic drugs for heart failure, i.e. diuretics, angiotensin-converting enzyme inhibitors, ß -blockers and cardiac glycosides, still play a major role in the treatment of pediatric heart failure, newer alternative therapies such as levosimendan and nesiritide are increasingly utilized with promising early results. A systematic literature search of PubMed and MEDLINE databases using relevant terms was performed. All clinical trials and relevant manuscripts about the current pharmacologic treatment of heart failure in the pediatric population were reviewed. New drugs such as levosimendan and nesiritide and the treatment of single-ventricle patients were also included.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Child; Diuretics; Heart Defects, Congenital; Heart Failure; Hemodynamics; Humans; Hydrazones; Incidence; Natriuretic Peptide, Brain; Pyridazines; Simendan

Recent studies have shown that not only plasma B-type natriuretic peptide (BNP)-32, but also plasma proBNP-108 is increased in heart failure (HF), and that the current BNP-32 assay kit crossreacts with proBNP-108. It also was shown that both BNP-32 and proBNP-108 were higher in HF than in normal. The proBNP-108/total BNP (BNP-32 + proBNP-108) ratio was widely distributed and patients with HF with ventricular overload had higher proBNP-108/total BNP ratio than HF patients with atrial overload. Consistent with this finding, proBNP-108 was the major molecular form in ventricular tissue, and BNP-32 was the major molecular form in atrial tissue. In addition, proBNP-108 was the major molecular form of BNP in pericardial fluid. The proBNP-108/total BNP ratio increased with deterioration of HF and decreased with improvement of HF. Thus, not only BNP-32, but also proBNP-108 is increased in HF and the proBNP-108/total BNP ratio also rises in association with pathophysiological conditions such as ventricular overload. A new hypothesis that O-glycosylation at Thr71 in a region close to the cleavage site impairs proBNP-108 processing was proposed. In the future, the precise mechanism of increased proBNP-108 in HF should be elucidated.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain

B-type Natriuretic Peptide (BNP) is a circulating hormone primarily produced by the myocardium in response to volume overload and increased filling pressure. BNP acts to increase natriuresis and to decrease cardiac load and blood pressure. The appearance of active BNP hormone in the bloodstream is preceded by the proteolytic cleavage of its precursor, proBNP. The products of proBNP processing, BNP and the N-terminal fragment of proBNP (NT-proBNP), have been extensively shown to be powerful biomarkers of heart failure (HF) and risk assessments for cardiovascular complications. In contrast to the clinical utility of proBNP-derived peptides, knowledge of posttranslational proBNP maturation and molecular aspects of its processing are far from being completely comprehended. A clear understanding of proBNP processing mechanisms in normal and diseased states appears to be required to improve our understanding of HF development and the clinical significance of both proBNP and proBNP-derived peptides. The aim of the present review is to summarize the available data in the field of human proBNP maturation and processing and to discuss potential clinical implications.

Topics: Animals; Glycosylation; Heart Failure; Humans; Natriuretic Peptide, Brain; Protein Precursors; Protein Processing, Post-Translational

The natriuretic peptides B-type natriuretic peptide (BNP) and NT-proBNP have been incorporated into the existing clinical guidelines for the diagnostic evaluation of heart failure. Recent evidence has provided important information regarding the relative value of each of these peptides to differentiate between pleural effusions caused by heart failure and those attributable to other causes.. In a meta-analysis of 10 studies, which included 1120 patients, pleural fluid levels of NT-proBNP had a pooled sensitivity and specificity of 94%, a positive likelihood ratio of 15.2, and a negative likelihood ratio of 0.06 in identifying heart failure-related effusions. Because pleural fluid and serum natriuretic peptide levels are closely correlated and display similar discriminatory properties, blood tests alone are sufficient. More than 85% of heart failure patients whose pleural fluids meet exudative criteria exhibit high pleural NT-proBNP concentrations. The diagnostic performance of pleural fluid BNP has been reported to be inferior to that of NT-proBNP.. NT-proBNP is an established biomarker of heart failure-associated effusions and the most effective tool for recognizing cardiac effusions that are misclassified as exudates by Light's criteria. If clinicians choose pleural fluid specimens for natriuretic peptide testing, the lower diagnostic accuracy of BNP makes it a poor substitute for NT-proBNP measurements.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Effusion

Diagnosing early stages of heart failure with mild symptoms is difficult. B-type natriuretic peptide (BNP) has promising biochemical test characteristics, but its diagnostic yield on top of readily available diagnostic knowledge has not been sufficiently quantified in early stages of heart failure.. To quantify the added diagnostic value of BNP for the diagnosis of heart failure in a population relevant to GPs and validate the findings in an independent primary care patient population.. Individual patient data meta-analysis followed by external validation. The additional diagnostic yield of BNP above standard clinical information was compared with ECG and chest x-ray results.. Derivation was performed on two existing datasets from Hillingdon (n=127) and Rotterdam (n=149) while the UK Natriuretic Peptide Study (n=306) served as validation dataset. Included were patients with suspected heart failure referred to a rapid-access diagnostic outpatient clinic. Case definition was according to the ESC guideline. Logistic regression was used to assess discrimination (with the c-statistic) and calibration.. Of the 276 patients in the derivation set, 30.8% had heart failure. The clinical model (encompassing age, gender, known coronary artery disease, diabetes, orthopnoea, elevated jugular venous pressure, crackles, pitting oedema and S3 gallop) had a c-statistic of 0.79. Adding, respectively, chest x-ray results, ECG results or BNP to the clinical model increased the c-statistic to 0.84, 0.85 and 0.92. Neither ECG nor chest x-ray added significantly to the 'clinical plus BNP' model. All models had adequate calibration. The 'clinical plus BNP' diagnostic model performed well in an independent cohort with comparable inclusion criteria (c-statistic=0.91 and adequate calibration). Using separate cut-off values for 'ruling in' (typically implying referral for echocardiography) and for 'ruling out' heart failure--creating a grey zone--resulted in insufficient proportions of patients with a correct diagnosis.. BNP has considerable diagnostic value in addition to signs and symptoms in patients suspected of heart failure in primary care. However, using BNP alone with the currently recommended cut-off levels is not sufficient to make a reliable diagnosis of heart failure.

Topics: Aged; Biomarkers; Electrocardiography; Family Practice; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Point-of-Care Systems; Sensitivity and Specificity

Topics: Acute Disease; Aged; Biomarkers; Diagnosis, Differential; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis

To assess the predictive value of B-type natriuretic peptide (BNP) in the diagnosis of heart failure (HF) in a primary-care setting in Spain.. PANAMA was a multicenter and cross-sectional study. Patients ≥18 years of age with a clinical diagnosis of HF (Framingham criteria) were consecutively included in the study by primary-care investigators. BNP determination and an echocardiogram were performed in every patient. The cut-off point of BNP for the criterion of exclusion of HF was considered as <100 pg/ml, as suggested by European guidelines. Sensitivity, specificity, positive-predictive value and negative-predictive value were calculated.. A total of 72 patients (mean age: 75.1 ± 8.7 years; 74.6% women) were included. The most frequent associated risk factors were hypertension (75.6%) and dyslipidemia (54.3%). The most common major and minor criteria of HF according to Framingham criteria were radiographic cardiomegaly (90.2%) and dyspnea on ordinary exertion (100%), respectively. BNP median was 49 pg/ml (33.3 pg/ml in those with a doubtful diagnosis of HF and 83.3 pg/ml in those with a likely diagnosis of HF). Approximately 60% of patients exhibited diastolic dysfunction. Concerning accuracy parameters comparing BNP >100 pg/ml with echocardiogram, sensitivity was 25%, the specificity 80.8%, and the positive- and negative-predictive values were 68.8 and 38.9%, respectively.. In patients attended by general practitioners, BNP >100 pg/ml may be a useful diagnostic tool with a high specificity for the diagnosis of HF.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Primary Health Care; Sensitivity and Specificity; Severity of Illness Index; Spain

Acute heart failure has emerged as the leading diagnosis among hospitalized patients, and challenges in accurate diagnosis, risk stratification and optimized management still remain. Here, biomarkers--with their low cost, objectivity and widespread availability--can play an indispensible role. Among the biomarkers available, natriuretic peptides (NPs) are the most validated and accepted for risk stratification and treatment guidance. The physiological basis for this lies in the strong correlation between NP levels and pulmonary capillary wedge pressure. The ability to classify individuals on the basis of risk could allow clinicians to tailor therapies to fit individual patient needs, thus reducing morbidity, mortality and costs.

Topics: Acute Disease; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Pulmonary Wedge Pressure

This review summarizes recent findings on novel biochemical plasma biomarkers in terminal heart failure patients, which might predict an advanced mortality risk or even recovery. Moreover, we discussed the regulation of these heart failure-related biomarkers under mechanical circulatory support.

Topics: Biomarkers; Galectin 3; Growth Differentiation Factor 15; Growth Differentiation Factor 5; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Interleukin-1 Receptor-Like 1 Protein; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Natriuretic Peptide, Brain; Receptors, Cell Surface; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases

Congestive heart failure is a very real public health issue not only in the United States, but worldwide. Mortality in patients with congestive heart failure is typically either sudden cardiac death or pump failure. Paradoxically, patients with less severe heart failure are at higher relative risk of sudden cardiac death. Defining which patients are best treated with implantable defibrillators and resynchronization is the purpose of this review.

Topics: Biomarkers; Cardiac Resynchronization Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Evidence-Based Medicine; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Myocardial Revascularization; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Stroke Volume

Neurohormonal activation in patients with heart failure is dominated by the deleterious long-term effects of activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. The natriuretic peptides, including brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), are also upregulated in heart failure, and partially counteract these deleterious effects by promoting vasodilation, natriuresis, and diuresis. Although BNP has been established as an important biomarker in the diagnosis and prognosis of heart failure, growing evidence suggests that measurement of plasma ANP, specifically its metabolite mid-regional pro-ANP, has similar diagnostic and prognostic value. Furthermore, its measurement may provide incremental diagnostic value when BNP levels fall into "grey zone" levels and may be a more potent prognostic marker of mortality.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis

Heart failure is the most frequent cause of hospitalization in elderly population. Unlike the therapy of congestive heart failure, there was only a modest progress in the medical treatment for acutely decompensated heart failure over the past several decades. Moreover, current treatment is associated with many limitations in clinical practice. The family of natriuretic peptides consists of several structurally similar polypeptides (ANP, BNP, CNP, urodilatin, DNP). ANP and BNP are the most characterized substances and represent an important compensatory mechanisms in heart failure because of their vasodilatory, natriuretic and antiproliferative effects. Nesiritide is a recombinant human BNP which has been shown to be effective in treating heart failure in several clinical trials. However, a recent meta-analysis revealed a nesiritide-associated increased 30-day-mortality rate. The results of initial small-sized trials suggest beneficial hemodynamic effects of urodilatin in decompensated heart failure. Despite of being approved for the treatment of decompensated heart failure in some countries, the clinical relevance of nesiritide is currently unclear. Urodilatin might represent a potential alternative.

Topics: Acute Disease; Atrial Natriuretic Factor; Diuretics; Drug Approval; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

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

Despite advances in device closure for atrial septal defect (ASD), post-closure heart failure observed in adult patients remains a clinical problem. Although right heart volume overload is the fundamental pathophysiology in ASD, the post-closure heart failure characterized by acute pulmonary congestion is likely because of age-related left ventricular diastolic dysfunction, which is manifested by acute volume loading with ASD closure. Aging also appears to play important roles in the pathophysiology of heart failure through several mechanisms other than diastolic dysfunction, including ventricular systolic and vascular stiffening and increased incidence of comorbidities that significantly affect cardiovascular function. Recent studies suggested that accurate assessment of preclosure diastolic function, such as test ASD occlusion, may help identify high-risk patients for post-closure heart failure. Anti-heart failure therapy before device closure or the use of fenestrated device appears to be effective in preventing post-closure heart failure in the high-risk patients. However, the long-term outcome of such patients remains to be elucidated. Future studies are warranted to construct an algorithm to identify and treat patients at high risk for heart failure after device closure of ASD.

Topics: Age Factors; Aging; Cardiac Catheterization; Heart Failure; Heart Rate; Heart Septal Defects, Atrial; Hemodynamics; Humans; Natriuretic Peptide, Brain; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ventricular Function, Left

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

Heart disease affects 1 in 3 individuals in the United States, and the prevalence of heart failure (HF) is increasing exponentially. Although our understanding of the disease progression of congestive HF (CHF) has advanced, refining the areas of diagnosis, risk stratification, prognosis, and treatment is still needed. The natriuretic peptides, specifically B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have shown promise in clinical practice. Brain natriuretic peptide is released from cardiac ventricular myocytes in response to volume or pressure overload. Rapid measurement of plasma BNP or NT-proBNP has been shown to increase the diagnostic accuracy of HF exacerbations. A cutoff value of 100 pg/mL has a sensitivity and specificity of 90% and 73%, respectively, according to the Breathing Not Properly Study. In addition, BNP and NT-proBNP have been considered independent predictors of adverse outcome. One study calculated a 35% increase in risk of death due to HF for every 100-pg/mL increase in BNP level. Lastly, natriuretic peptides have been known to decrease following medical therapy of HF, suggesting the role of their measurement in monitoring inpatient disease progression and outpatient medical programs. The future of natriuretic peptides lies in risk stratification in other cardiac diseases, such as acute coronary syndrome, and possibly determining severity of valvular disease. Although there is substantial work done in elucidating the power of natriuretic peptides in clinical practice, more research is necessary to reach a consensus regarding how to appropriately utilize them in treatment regimens.

Topics: Acute Coronary Syndrome; Biomarkers; Cardiovascular Agents; Heart Failure; Heart Valve Diseases; Humans; Mass Screening; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Sensitivity and Specificity

Brain natriuretic peptide (BNP) is a major marker for evaluating cardiac function and has been widely used in clinical practice. Recent researches show that BNP is also useful for identification of sudden cardiac death in forensic pathology. This article reviews the molecular structure and biological characteristics of the BNP and its application as a functional indicate in forensic medicine. It shows that the expression of BNP in cardiac muscles, together with the expression of BNP in blood and pericardium liquid can be used to evaluate the pathological physiology changes and dysfunction degrees of the heart during the cardiac sudden death.

Topics: Amino Acid Sequence; Animals; Autopsy; Biomarkers; Death, Sudden, Cardiac; Forensic Pathology; Heart Diseases; Heart Failure; Humans; Immunohistochemistry; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Pericardium; Postmortem Changes; RNA, Messenger

In this review we have looked at indications for cardiac transplantation in congenital heart disease. An outline of the general principles of the use of transplant as a management strategy both as a first line treatment and following other surgical interventions is discussed. We explore the importance of the timing of patient referral and the evaluations undertaken, and how the results of these may vary between patients with congenital heart disease and patients with other causes of end-stage heart failure. The potential complications associated with patients with congenital heart disease need to be both anticipated and managed appropriately by an experienced team. Timing of transplantation in congenital heart disease is difficult to standardize as the group of patients is heterogeneous. We discuss the role and limitations of investigations such as BNP, 6 minute walk, metabolic exercise testing and self estimated physical functioning. We also discuss the suitability for listing. It is clear that congenital heart patients should not be considered to be at uniform high risk of death at transplant. Morbidity varies greatly in the congenital patient population with the failing Fontan circulation having a far higher risk than a failing Mustard circulation. However the underlying issue of imbalance between donor organ supply and demand needs to be addressed as transplant teams are finding themselves in the increasingly difficult situation of supporting growing numbers of patients with a diverse range of pathologies with declining numbers of donor organs.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Heart Defects, Congenital; Heart Diseases; Heart Failure; Heart Function Tests; Heart Transplantation; Humans; Infant; Medical History Taking; Natriuretic Peptide, Brain; Preoperative Care; Respiration, Artificial; Tissue Donors; Young Adult

Heart failure (HF) is a modern epidemic and is one of the few cardiovascular diseases which is increasing in prevalence. The growing importance of the Natriuretic Peptide (NP) system in HF is well recognized. Laboratory tests for B-type Natriuretic Peptide (BNP) have proven value as diagnostic and prognostic tools in HF and are now part of routine clinical care. Furthermore, recombinant atrial natriuretic peptide (ANP) (carperitide) and BNP (nesiritide) and are approved HF therapies in Japan and the US, respectively and additional natriuretic peptides (e.g., CNP, urodilatin, and designer NPs) are under investigation for use in HF. Common genetic sequence variants are increasingly being recognized as determinants of disease risk or drug response and may help explain a portion of the inter-individual variation in the human NP system. This review describes current knowledge of NP system genetic variation as it pertains to HF as well as ongoing studies and where the field is expected to progress in the near future. To briefly summarize, NP system genetic variants have been associated with alterations in gene expression, NP levels, and cardiovascular disease. The next step forward will include specific investigations into how this genetic variation can advance 'Personalized Medicine', such as whether they impact the utility of diagnostic BNP testing or effectiveness of therapeutic NP infusion. This is already in progress, with pharmacogenetic studies of nesiritide currently underway. We expect that within 5 years there should be a reasonable idea of whether NP system genetic variation will have important clinical implications.

Topics: Atrial Natriuretic Factor; Genetic Variation; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Pharmacogenetics; Prevalence; Prognosis; Receptors, Atrial Natriuretic Factor; Risk Factors; Treatment Outcome

The B-type natriuretic peptide (BNP) and the amino-terminal fragment of proBNP (NT-proBNP) are increased in heart failure in proportion to severity of symptoms, degree of left ventricular dysfunction, and elevation of cardiac filling pressures. These natriuretic peptides (NPs) are increasingly used for diagnostic and prognostic purposes in acute heart failure. While NP levels on admission provide independent prognostic information, serial determinations during hospitalization and at discharge better reflect adequacy of treatment and prognosis. The addition of BNP and NT-proBNP to usual clinical decision making enhances detection of high-risk patients who need aggressive follow-up and adjustment of treatment.

Topics: Acute Disease; Diabetes Mellitus; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; United States; Ventricular Dysfunction, Left

N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) has emerged as an important adjunct in the management of heart failure (HF) and other cardiovascular diseases. NT-proBNP is a 76-amino acid peptide created during cleavage of the precursor molecule, Pro B-type natriuretic peptide (ProBNP). NT-proBNP is of significant diagnostic value in patients presenting with possible HF and is an important prognostic factor in this condition and other cardiovascular diseases. Ongoing research supports the potential value of this biomarker in non-cardiovascular disease. This review will describe clinical applications of NT-proBNP in HF and a broad range of other conditions.

Topics: Biomarkers; Cardiovascular Diseases; Coronary Artery Disease; Diastole; Dyspnea; Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases; Prognosis; Ventricular Function, Left

The management of heart failure remains challenging despite many therapeutic advances. Rigorous clinical trial evidence supports administration of multiple therapies, but utilization of evidence-based treatment remains inconsistent and suboptimal. Disease management programs appear effective, but remain costly and difficult to implement in today's care system. Another approach involves optimizing therapy based on serial monitoring of cardiac biomarkers. Emerging results suggest that guiding therapy based on serial changes in natriuretic peptides may be an effective strategy. Although pilot work has provided encouraging results, appropriately designed, large-scale, prospective randomized trials are needed to confirm these preliminary findings and definitively establish this therapeutic approach.

Topics: Area Under Curve; Biomarkers; Cardiotonic Agents; Disease Management; Drug Monitoring; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis; Treatment Outcome; Troponin

Advances in genomics and proteomics promise to transform biomarker research, in which the major challenges will not be the discovery of new markers but rather the optimal selection and validation of a subgroup of clinically useful markers from the large pool of candidates. Critically, the value of new biomarkers panels will need to be assessed in the context of readily available clinical information in order to create more actionable knowledge rather than just greater complexity. Appropriate methodologies for the clinical and statistical evaluation of so called "multi-marker strategies" have not been systematically defined. Although specific criteria for the appropriate clinical and statistical evaluation of multi-marker strategies will vary based on the intended use (e.g., diagnosis vs. screening), the ultimate measure of success is the ability for a biomarker panel to both correct a meaningful portion of misclassification by standard methods (discrimination) and to improve quantification of absolute risk (calibration) in comparison to existing clinical information. Findings should be validated in an independent dataset of the representative patient population before a given multi-marker strategy can be considered for clinical use. Here, we define multi-marker strategies, summarize recent examples of biomarker combinations in heart failure, address key statistical and clinical issues, and discuss future directions for this rapidly evolving field.

Topics: Biomarkers; Data Interpretation, Statistical; Genomics; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Proteomics; Risk Assessment; ROC Curve

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biomarkers in the diagnosis and risk stratification for heart failure (HF). These peptides are synthesised as inactive precursors, pro-ANP and pro-BNP, which are converted to biologically active 28 amino acid ANP and 32 amino acid BNP, respectively. Most immunoassays currently used in the clinical setting, however, do not determine precise molecular forms of these natriuretic peptides, which may vary depending on the pathophysiological state of HF. Analysis from chromatography-based studies reveals that in HF inactive pro-ANP and pro-BNP forms often predominate. This indicates that the bioactive forms of natriuretic peptides may not be processed proportionally in patients with advanced HF. Distinguishing the bioactive natriuretic peptides from their inactive forms in plasma may help to define the role of these peptides in the pathogenesis of HF and provide new insights into the treatment of the disease.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain

BNP and the N-terminal portion (NT-pro-BNP) have emerged as powerful tools in the diagnosis and prognosis of heart failure on acute presentation. The aim of this work was to systematically review the effect of exercise training on BNP and NT-pro-BNP levels in patients with left ventricular dysfunction.. A systematic search was conducted of Medline (Ovid) (1950-July 2008), Embase.com (1974-current), Cochrane Central Register of Controlled Trials, CINAHL (1981-current) and Web of Science (2000-current) to identify randomized controlled trials of aerobic and/or resistance exercise training in heart failure patients that measured BNP and/or pro-BNP. Primary outcome measures were changes in BNP and NT-pro-BNP. Secondary outcomes were changes in functional capacity and energy expenditure, measures of study quality were also recorded.. Nine randomized controlled studies measuring BNP or NT-pro-BNP met our eligibility criteria. Exercise training had a favourable effect on BNP (mean difference -79 pg/ml 95% C.I. -141 to - 17 pg/ml, P=0.01) and NT-pro-BNP (mean difference -621 pg/ml, 95% C.I. -844 to -398 pg/ml, P=<0.00001). Moreover the trials that showed a significant change in NT-pro-BNP all had a weekly exercise energy expenditure of more than 400 Kcal.. Data from nine published studies, suggest exercise training has a favorable effect on BNP and NT-pro-BNP in heart failure patients.

Topics: Biomarkers; Exercise; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Resistance Training; Ventricular Dysfunction, Left

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Testing for natriuretic peptide markers, such as B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP), has emerged as an important tool for the diagnosis and risk stratification of patients with HF. However, questions remain regarding the potential role for natriuretic peptides to guide therapy in patients with HF. In this Review, we address the underlying assumptions and the existing evidence supporting a natriuretic-peptide-guided approach to the outpatient management of HF.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Diuretics; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Risk Factors; Spironolactone

Acute decompensated heart failure is a common clinical problem with associated poor outcomes. Over the last decade, attention to this area has greatly increased, with a focus on medical therapies that may safely offer improvement in acute symptoms and early outcomes. Previous therapies that focused on increased inotropy have generally failed to improve symptoms without adverse consequences. Thus, attention towards vasodilators and natriuretic peptides, such as nesiritide, has increased owing to nesiritide's symptomatic improvement and unique mechanism of improvement in hemodynamics. However, the pathophysiology of acute decompensated heart failure is complex and the impact of nesiritide on important clinical end points, beyond symptomatic and hemodynamic improvement, is unknown.

Topics: Acute Disease; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Vasodilator Agents

Heart failure is an important cardiac disease with an increasing prevalence in Western societies. In addition to a significant reduction of the patient's physical capability and quality of life, cardiac insufficiency is associated with considerable expenditure by national health care systems. A number of imaging techniques are available for the detection of heart failure (e.g., echocardiography), and the use of biomarkers such as brain natriuretic peptides (BNP or NT-proBNP) becomes increasingly popular in the process of screening and diagnosis. Until now, there is a lack of information regarding health-economic aspects of this biomarker use. For this reason, a systematic literature search was conducted in MEDLINE including all relevant studies published up to and including August 2009. The primary objective was to summarize the main findings of all relevant investigations which focus on health-economic aspects of BNP use as well as NT-proBNP use. Out of 64 initial search results, 13 relevant studies were identified which met the inclusion criteria. Eleven studies were finally included in this literature review. Although the methodology of these studies was very heterogeneous, the majority of investigations indicate that the use of BNP and NT-proBNP, respectively, is a cost-effective procedure for heart failure diagnosis and prognosis, as well as for heart failure screening. However, keeping in mind that the transferability of economics study results is limited due to a number of differences between national health care systems, there are no investigations with a focus on the financial implications for Germany. Further research is required in this context.

Topics: Biomarkers; Cost-Benefit Analysis; Echocardiography; Heart Failure; Humans; National Health Programs; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Sensitivity and Specificity

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 randomized controlled trials (RCTs). However, the benefits of this treatment approach have been uncertain. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on cardiovascular outcomes in patients with chronic HF.. We identified RCTs by systematic search of manuscripts, abstracts, and databases. Eligible RCTs were those that enrolled more than 20 patients and involved comparison of BNP-guided drug therapy vs usual clinical care of the patient with chronic HF in an outpatient setting.. Eight RCTs with a total of 1726 patients and with a mean duration of 16 months (range, 3-24 months) were included in the meta-analysis. Overall, there was a significantly lower risk of all-cause mortality (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = .003) in the BNP-guided therapy group compared with the control group. In the subgroup of patients younger than 75 years, all-cause mortality was also significantly lower in the BNP-guided group (RR, 0.52; 95% CI, 0.33-0.82; P = .005). However, there was no reduction in mortality with BNP-guided therapy in patients 75 years or older (RR, 0.94; 95% CI, 0.71-1.25; P = .70). The risk of all-cause hospitalization and survival free of any hospitalization was not significantly different between groups (RR, 0.82; 95% CI, 0.64-1.05; P = .12 and RR, 1.07; 95% CI, 0.85-1.34; P = .58, respectively). The additional percentage of patients achieving target doses of angiotensin-converting enzyme inhibitors and beta-blockers during the course of these trials averaged 21% and 22% in the BNP group and 11.7% and 12.5% in the control group, respectively.. B-type natriuretic peptide-guided therapy reduces all-cause mortality in patients with chronic HF compared with usual clinical care, especially in patients younger than 75 years. A component of this survival benefit may be due to increased use of agents proven to decrease mortality in chronic HF. However, there does not seem to be a reduction in all-cause hospitalization or an increase in survival free of hospitalization using this approach.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Treatment Outcome

The mature, biologically active 32-amino acid long B-type natriuretic peptide (BNP(1-32)), is cleaved by corin from the BNP prohormone. Recent data demonstrated that BNP(1-32) might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase (DPP) IV. DPP IV removes the two amino-terminal amino acids (Ser and Pro) from BNP(1-32) to produce BNP(3-32), which has been detected in plasma of patients with heart failure. In a canine model, intravenous BNP(3-32) infusion resulted in less natriuresis, diuresis and vasodilation compared to intravenous infusion of BNP(1-32). The clinical relevance of these observations may be important for patients with high plasma BNP concentrations, which can be measured by commercially available immunoassays. Further studies are needed to explore whether DPP IV inhibitors increase the bioavailability of BNP(1-32), delay the progression of heart failure and increase the efficacy of exogenously administered BNP(1-32) in decompensated heart failure.

Topics: Animals; Biomarkers; Disease Progression; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Peptide Fragments

The key management goals for the stabilization of patients admitted for acutely decompensated heart failure (ADHF) include relief of congestion and restoration of hemodynamic stability. Nevertheless, in spite of clinical improvement, many patients are discharged with hemodynamic congestion. In response to volume expansion, the heart secretes the brain natriuretic peptide (BNP) with a biological action that counter-regulates the activation of the renin-angiotensin-aldosterone system. Since BNP is released by increased volume load and wall stretch, and declines after treatment with drugs of proven efficacy, on the basis of an improvement in filling pressures the level of BNP has been proposed as a 'measure' of congestion. The BNP level of a patient who is admitted with ADHF comprises two components: a baseline, euvolemic 'dry' BNP level and a level induced by volume or pressure overload ('wet' BNP level). So, the prognostic value of BNP during hospitalization depends on the time of measurement: from the lowest on admission when congestion is present (wet BNP) to the highest on clinical and instrumental stability (dry BNP), following the achievement of normohydration, as determined by fluid volume measurement. Euvolemia can be set as the primary goal of treatment for ADHF with dry BNP concentration as a target for discharge other than improvement of symptoms, because high BNP levels predict rehospitalization and death. Discharge criteria utilizing both BNP and hydration status measurement which account for the heterogeneity of the patient population and incorporate different strategies of care should be developed. This could in the next future offer an aid in monitoring heart failure patients or actively guiding optimal titration of therapy.

Topics: Biomarkers; Electric Impedance; Heart Failure; Humans; Natriuretic Peptide, Brain; Water-Electrolyte Imbalance

The impact of cardiac dysfunction and heart failure is continuing to escalate in the developed world. Treatment of this heterogeneous condition has focused on the symptomatic stage, often after irreversible remodeling and functional impairment have occurred. Early identification of cardiac dysfunction would allow implementation of early intervention strategies to delay the progression or to prevent the onset of heart failure altogether. Although screening methods for asymptomatic cardiac dysfunction have yet to be optimized, a staged approach for patients with predisposing risk factors using serological biomarkers followed by noninvasive imaging techniques may be useful. Existing biomarkers for cardiac dysfunction include B-type natriuretic peptide, troponins, and C-reactive protein. Novel markers such as protein ST2, galectin-3, and various prohormones are emerging and may provide prognostic information that is incremental to conventional clinical evaluation. Monitoring myocardial mechanics and molecular processes through three-dimensional speckle tracking and hybrid imaging modalities, such as PET-CT, may provide insight into disease manifestation before overt structural and physiological abnormalities.

Topics: Biomarkers; C-Reactive Protein; Disease Progression; Galectin 3; Heart Diseases; Heart Failure; Humans; Myocardium; Natriuretic Peptide, Brain; Positron-Emission Tomography; Prognosis; Risk Factors; Time Factors; Tomography, X-Ray Computed; Troponin

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker useful in diagnosis of pleural effusion due to heart failure. Thus far, its overall diagnostic accuracy has not been systematically reviewed. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of pleural NT-proBNP for identifying pleural effusion due to heart failure.. After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of NT-proBNP concentrations in pleural fluid in the diagnosis of pleural effusion resulting from heart failure were pooled using fixed-effects models. Summary receiver operating characteristic curves were used to summarise overall test performance.. Eight publications met the inclusion criteria. The summary estimates for pleural NT-proBNP in the diagnosis of pleural effusion attributable to heart failure were: sensitivity 0.95 (95% CI 0.92 to 0.97), specificity 0.94 (0.92 to 0.96), positive likelihood ratio 14.12 (10.23 to 19.51), negative likelihood ratio 0.06 (0.04 to 0.09) and diagnostic OR 213.87 (122.50 to 373.40).. NT-proBNP levels in pleural fluid showed a high diagnostic accuracy and may help accurately differentiate cardiac from non-cardiac conditions in patients presenting with pleural effusion.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Effusion; Publication Bias; Sensitivity and Specificity

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

Topics: Abdomen, Acute; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis

Topics: Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Digoxin; Diuretics; Dyspnea; Echocardiography; Edema; Exercise Tolerance; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Patient Education as Topic; Referral and Consultation; Terminal Care; Ventricular Dysfunction, Left

Biomarkers can provide insights into underlying mechanisms and lead to better understanding of complex disease states. This enhanced understanding can then be integrated into disease management, which can lead to better therapies and ultimately to improved patient outcomes. The natriuretic peptides (NPs) are established cost-effective biomarkers in heart failure and have set the standard for how a well-validated biomarker can be useful in the diagnosis/prognosis, monitoring of response to therapy, and management of chronic disease. Newer biomarkers such as midregional pro-adrenomedullin, ST2, and neutrophil gelatinase-associated lipocalin are emerging as adjuncts to NPs in the management of heart failure patients.

Topics: Acute-Phase Proteins; Atrial Natriuretic Factor; Biomarkers; Guanosine Monophosphate; Heart Failure; Humans; Interleukin-1; Lipocalin-2; Lipocalins; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proto-Oncogene Proteins; Risk Factors

Cardiac natriuretic peptides, BNP and NT-proBNP can be used to screen for left ventricular systolic dysfunction in patients with symptoms suggestive of heart failure. Using the cut-off values recommended in the article, the sensitivity and negative predictive values are high in patients aged < 75 years, but have lower sensitivity at older age. In addition, natriuretic peptides are prognostic markers for mortality and cardiovascular hospitalization. BNP/NT-proBNP measurement may also be of value in follow-up on heart failure patients.

Topics: Age Factors; Aged; Biomarkers; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reference Values; Risk Factors; Sensitivity and Specificity; Ventricular Dysfunction, Left

Previous randomized controlled trials (RCTs) evaluating nesiritide for the treatment of acute decompensated heart failure (ADHF) have reported wide variances in mortality hazard ratios for nesiritide vs controls, but these individual trials were neither designed nor powered to evaluate mortality. This study used relevant data from all RCTs of nesiritide in ADHF completed as of June 2006 to independently estimate the effect of nesiritide on 30- and 180-day mortality.. Administration of nesiritide to treat patients with ADHF does not significantly increase mortality at 30 or 180 days.. Six trials met prespecified criteria for inclusion in this analysis. Primary data from these trials were obtained from Scios Inc. (Fremont, CA). Statistical models were fitted to estimate 4 effects: dose response, differing control groups, vulnerable subgroup interactions, and time of death relative to nesiritide administration. All models included 4 baseline covariates that were significantly and independently associated with mortality.. Complete covariate data were available in 1472 of 1538 subjects (96%). The risk-adjusted hazard ratio for mortality was 1.05 (95% confidence interval [CI]: 0.85-1.30) at 30 and 1.00 (95% CI: 0.88-1.14) at 180 days with no clear relationship to nesiritide dose. In addition to consistent results across 2 time points, no significant evidence of sensitivity to control group or baseline risk factors was found.. Currently available data suggest nesiritide does not significantly increase mortality at 30 or 180 days.

Topics: Acute Disease; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Renin-angiotensin aldosterone system (RAAS) activation is a key neurohormonal contributor to the progression of chronic heart failure. Strategies that block this activation have consistently demonstrated major beneficial impacts on morbidity and mortality in this setting. Direct renin inhibitors (DRIs) present a novel opportunity to block at an additional or alternative step in this pathway, that being conversion of angiotensinogen to angiotensin I. Theoretical benefits of blocking at the level of renin include: inhibition of the reflex activation of plasma renin activity induced by conventional downstream RAAS blockers. Minimization of angiotensin II and/or aldosterone escape and blocking upstream at the rate-limiting step of angiotensin I production. Preclinical and early-phase clinical studies have largely supported this hypothesis. In the Aliskiren Observation of Heart Failure Treatment study, patients with systolic chronic heart failure receiving background angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers and β-blockers benefited from aliskiren in reduction vs placebo of plasma levels of brain natriuretic peptide, the primary efficacy endpoint of that study. Large-scale outcome trials are, however, required to definitively determine the benefits of a DRI strategy additional to, or as an alternative to, conventional approaches such as ACE inhibitors in the systolic chronic heart failure setting. Copyright © 2010 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Adrenergic beta-Antagonists; Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Disease Progression; Fumarates; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Renin; Renin-Angiotensin System

Since the discovery of atrial natriuretic peptide (ANP), there has been tremendous progress in our understanding of the physiologic and pathophysiologic, diagnostic, and therapeutic roles of ANP. The diagnostic application of ANP and brain natriuretic peptide (BNP) has been reviewed by many investigators, and meta-analyses of therapeutic use of BNP were reported from the USA. However, there are few reviews concerning the therapeutic use of ANP in patients with various conditions. Therefore, this review focuses on the recent clinical evidence of ANP in therapeutic use and experimental data that rationally support the therapeutic use of ANP.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Diseases; Mice; Myocardial Infarction; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Receptors, Atrial Natriuretic Factor; Ventricular Remodeling

Cardiovascular diseases are a leading cause of hospitalizations and death in the United States and elsewhere in the world. Developing new therapeutic agents for cardiovascular diseases has always been the priority for the pharmaceutical industry because of the huge potential market for these drugs. Some of these newer drugs are frequently used in the practice of cardiovascular anesthesiology. This article reviews the recent advances in cardiovascular medications related to the practice of cardiac anesthesia.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Diastole; Heart Failure; Humans; Hydrazones; Muscle Contraction; Myofibrils; Natriuretic Peptide, Brain; Nicardipine; Pyridazines; Pyridines; Sarcomeres; Simendan; Urea

Several studies have been published in the literature on the diagnostic accuracy of NT-pro-BNP for pleural effusions from heart failure in the last decade. The purpose of our study was to perform a systematic review and meta-analysis on the diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin.. MEDLINE, EMBASE, PapersFirst, and the Cochrane collaboration and the Cochrane Register of controlled trials were searched. All searches were inclusive as of March 2010. Studies were only included if the absolute number of true-positive, false-negative, true-negative, and false-positive observations were available, and the "reference standards" were described clearly. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Quality Assessment for Diagnostic Accuracy Studies (QUADAS). The bivariate model for diagnostic meta-analysis was used to obtain a pooled sensitivity and a pooled specificity.. Ten studies (total number of patients 1120) were included in the meta-analysis. The average pleural fluid NT-pro-BNP level in effusions of cardiac origin was 6140 pg/mL. The pooled sensitivity and specificity of all studies combined was 94% (95% CI: 90-97) and 94% (95% CI: 89-97) respectively. The pooled positive likelihood ratio was 15.2 (95% CI: 8.1-28.7) and the pooled negative likelihood ratio was 0.06 (95% CI: 0.03-0.11). The area under the ROC curve was 0.98 (95% CI: 0.96-0.99) and the diagnostic odds ratio was 246 (95% CI: 81-745).. Pleural fluid NT-pro-BNP is a very useful biomarker with high diagnostic accuracy for distinguishing pleural effusions of cardiac origin.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Cavity; Pleural Effusion; Sensitivity and Specificity

Although the accuracy of B-type natriuretic peptide (BNP) testing for diagnosing acute decompensated heart failure has been extensively evaluated, the effect of this test on clinical outcomes remains unclear.. To investigate whether BNP testing of patients presenting with acute dyspnea in the emergency department leads to fewer admissions, shorter length of stay, and improved short-term survival compared with usual care without BNP testing.. Two reviewers searched Ovid MEDLINE and EMBASE, without language restrictions, to identify pertinent studies published from January 1996 to July 2010.. Randomized, controlled trials that compared BNP testing to diagnose heart failure with routine care in patients presenting with acute dyspnea and information about 1 or more of the following outcomes: mortality, admission, or length of hospital stay.. Two authors independently reviewed articles, extracted data, and assessed quality and risk for bias of studies.. Five trials conducted in 5 countries and involving 2513 patients met inclusion criteria. Study settings had differing emergency department staffing models and used various BNP testing protocols. The pooled estimate of effect of BNP testing on all-cause mortality had wide confidence bounds and was inconclusive (odds ratio, 0.96 [95% CI, 0.65 to 1.41]). Admission rates decreased in the tested group compared with the control group (odds ratio, 0.82 [CI, 0.67 to 1.01]), although this finding was not statistically significant. Length of hospital and critical care unit stay were both modestly reduced in the tested group compared with the control group, with a mean difference of -1.22 days (CI, -2.31 to -0.14 day) and -0.56 day (CI, -1.06 to -0.05 day), respectively.. Few relevant trials were studied. Patients included in the trials and the settings in which trials were conducted were heterogeneous.. B-type natriuretic peptide testing in the emergency department for patients presenting with acute dyspnea decreased length hospital of stay by about 1 day and possibly reduced admission rates but did not conclusively affect hospital mortality rates.. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Topics: Aged; Biomarkers; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome

Heart failure is a common cardiovascular disease with high morbidity and mortality. Unlike western countries where heart failure is predominantly a disease of the elderly, in India it affects younger age group. Important risk factors include coronary artery disease, hypertension, diabetes mellitus, valvular heart disease and cardiomyopathies. Plasma brain natriuretic peptide levels are helpful in the diagnosis of heart failure. Echocardiography is the primary imaging modality of choice, through recently cardiac magnetic resonance imaging (MRI) has been found to play an increasing role. Aim of management is to improve symptoms & enhance survival. Diuretics are important in relieving symptoms. Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and adosterone antagonists improve survival in patients with impaired systolic function. Device therapy including cardiac resynchronization therapy and implantable cardiac defibrillators, though expensive are useful in selected patients. Unlike in patients with systolic heart failure where several therapies have been shown to improve survival, clinical trial results in diastolic heart failure have been disappointing and therapy in these patients is restricted to symptom improvement and risk factor control. Therapies like stem cell therapy are being evaluated in clinical trials and appear promising. Early diagnosis and appropriate therapy helps in reversing the process of remodelling and clinical improvement in most of the patients.

Topics: Antihypertensive Agents; Biomarkers; Cardiac Resynchronization Therapy; Defibrillators, Implantable; Disease Management; Diuretics; Echocardiography; Electrocardiography; Heart Failure; Humans; Incidence; India; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Prevalence

In heart failure (HF), pleural effusion results from increased interstitial fluid in the lung due to elevated pulmonary capillary pressure. Rarely, pleural effusions may occur in association with isolated right HF. HF-associated effusions are typically bilateral, but if unilateral, they are more commonly seen on the right side. The fluid typically meets the biochemical characteristics of a transudate, although in 25% of the cases it may fall into the exudative range. Testing for natriuretic peptides, such as NT-proBNP, significantly aids in diagnosing or excluding HF in patients with pleural effusion of unknown origin. The measurement of pleural fluid NT-proBNP is the best way to identify pleural effusions that meet the exudative criteria of Light but are due to HF. However, if natriuretic peptide assays are not available, calculation of the serum to pleural fluid albumin gradient represents a good substitute for making this distinction. Loop diuretics are the mainstay of therapy, although a therapeutic thoracentesis for very large effusions may occasionally be required.

Topics: Albumins; Exudates and Transudates; Heart Failure; Humans; Natriuretic Peptide, Brain; Paracentesis; Peptide Fragments; Pleural Effusion; Sodium Potassium Chloride Symporter Inhibitors

Atrial fibrillation (AF) is the most common arrhythmia in the medical practice, it is associated with an increased total and cardiovascular mortality, as well as cardiovascular morbidity, including stroke and heart failure. AF is encountered in different medical specialties including cardiology, family medicine and emergency medicine as well. Treatment goal is to minimize stroke risk but also taking into account the quality of life. Therefore rate or a rhythm control strategies must be carefully selected. This review focuses on natriuretic polypeptides (NPs) as potential useful markers in AF patients management.. Pubmed was searched for natriuretic peptides and atrial fibrillation. Pertinent abstracts were reviewed by the Authors and the articles fully evaluated when considered pertinent.. NP biology and physiology is described and general application in heart failure outlined. With regard to AF, the role of NP as predictor of cardioversion is reviewed and discussed. Patients eligible for rhythm control not always respond to treatment. Classic markers for a suitable cardioversion, such an echocardiography, are not immediately available in most settings. NP might be a resource predicting cardioversion (or not) upon patient's presentation.. Biomarkers, such NPs, might be used to predict treatment response other than in heart failure.. In AF management, NT-ProBNP is a promising tool helping physicians to choose rhythm or rate control strategy.

Topics: Atrial Fibrillation; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments

The approach to the diagnosis of heart failure is complex, but the diagnostic armamentarium has increased significantly in the past decade. Diagnostic markers such as B-type natriuretic peptide and NT pro-B-type natriuretic peptide have proven value for the diagnosis of heart failure over and above the traditional tools that included only the history, physical examination, and chest radiography. Invasive and noninvasive impedance cardiography can be used to diagnose or even predict development of heart failure, but its role in clinical practice still needs to be better defined.

Topics: Biomarkers; Cardiography, Impedance; Diagnosis, Differential; Dyspnea; Electrocardiography; Heart Failure; Humans; Medical History Taking; Natriuretic Peptide, Brain; Peptide Fragments; Phonocardiography; Physical Examination; ROC Curve; Sensitivity and Specificity; Triage; Troponin I

Effective use of diuretics, vasodilators, and inotropes to stabilize acute heart failure (AHF) relies on matching the most appropriately tailored therapy to specific clinical profiles. Some of the drugs may be harmful, and therefore the emphasis should be on patient safety and the attempt to minimize the deleterious effects of these therapies. To date, successful treatment has been limited because no agent has been shown to reduce postdischarge mortality or readmission rates, and patients frequently remain symptomatic after treatment. Ongoing research is needed to further examine these agents and to develop novel therapies to address the unmet needs of the patient who has AHF.

Topics: Algorithms; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Diuretics; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Vasodilator Agents

Acute decompensated heart failure (ADHF) is a common illness presenting to the emergency department (ED) that is amenable to observation unit (OU) treatment. As the number of baby boomers continues to grow and the incidence of heart failure increases, the financial implications of ADHF treatment will become more prominent. Obtaining institutional support and developing a good working relationship with cardiology colleagues is vital to creating workable ADHF protocols for whichever type of OU an institution decides to use.

Topics: Acute Disease; Adrenergic beta-Antagonists; Antihypertensive Agents; Centers for Medicare and Medicaid Services, U.S.; Clinical Protocols; Cost-Benefit Analysis; Emergency Service, Hospital; Heart Failure; Hospitalization; Humans; Hydralazine; International Classification of Diseases; Length of Stay; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Selection; Positive-Pressure Respiration; United States

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebo-controlled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. Unfortunately, most of this discussion is only partially evidence based due to lack of appropriate clinical trials. In general, we believe that vasodilators should be administered early to AHF patients with normal or high blood pressure (BP) at presentation. They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients' outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1-2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice.

Topics: Acute Disease; Atrial Natriuretic Factor; Benzoates; Elapid Venoms; Endothelin-1; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nitrates; Peptide Fragments; Prognosis; Pyridines; Receptors, Endothelin; Relaxin; Tetrazoles; Vasoconstriction; Vasodilator Agents

Acute decompensated heart failure (ADHF) is a major public health issue and remains a heterogeneous, complex, and difficult condition to manage. Although novel acute therapies are being tested in large randomized clinical trials, opportunities exist to improve the standard of care by ensuring optimal adherence to currently established evidence-based interventions for HF. Consideration of the goals of therapy and practical application of current methods to assess for clinical improvement may lead to improved patient management and possibly improved outcomes for patients with ADHF. This review provides key practical information regarding the current standard of care for patients with ADHF including the goals of therapy, management of acute and chronic medications, and discharge/transition of care planning.

Topics: Acute Disease; Cardiovascular Agents; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Discharge

Clinical heart failure has been defined for a long time as a clinical syndrome with symptoms and signs including shortness of breath, cyanosis, ascites, and edema. However, in recent years, with the thought of promoting early diagnosis and heart-failure prevention, the concept of heart failure has often been defined simply as a subject with severe LV dysfunction and a dilated left ventricle, or by some, defined by evidence of increased circulating levels of molecular markers of cardiac dysfunction, such as ANP and BNP. Heart failure has been considered an irreversible clinical end point. Current medical management for heart failure only relieves symptoms, slows deterioration, and prolongs life modestly. However, in the recent years, rejuvenation of the failing myocardium began to seem possible as the accumulating preclinical studies demonstrated that rejuvenating the myocardium at the molecular and cellular level can be achieved by gene therapy or stem cell transplantation. Here, we review selected novel modalities that have been shown in preclinical studies to exert beneficial effects in animal models of severe LV dysfunction and seem to have the potential to make an impact in the clinical practice of heart-failure management.

Topics: Animals; Atrial Natriuretic Factor; Genetic Therapy; Heart Failure; Humans; Natriuretic Peptide, Brain

Pulmonary congestion can be challenging to diagnose because of nonspecific symptoms and the blunt nature of physical examination and radiographic findings. Assessing for euvolemia following treatment of congestion also can be difficult but can improve both the inpatient and outpatient care of patients who have heart failure. Tools such as the natriuretic peptides are important adjuncts to the physical examination and chest radiographs and often obviate the need for invasive hemodynamic assessment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Physical Examination; Predictive Value of Tests; Prognosis; Pulmonary Wedge Pressure

This article addresses a question that the authors consider to be somewhat rhetorical: are hemodynamic parameters predictors of mortality? It reviews the specific hemodynamic abnormalities and pathophysiologic consequences distinctive to the patient who has decompensation and addresses the data that implicate abnormal hemodynamics as a treatment target associated with increased mortality. The focus is on patients who have decompensated heart failure, defined as left ventricular systolic dysfunction and an acute, subacute, or gradual worsening of symptoms while receiving optimal medical therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Body Weight; Cardiac Output; Heart Failure; Hemodynamics; Hospitalization; Humans; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Sensitivity and Specificity; Ventricular Function, Left; Ventricular Pressure

The pulmonary artery catheter will likely earn a place in the history of medicine as one of the most useful tools that shaped our understanding and management of various diseases. An intense assessment of its application in nonacute and nonshock decompensated heart failure has been provided by the ESCAPE trial, a landmark investigation that showed an overall neutral impact of pulmonary artery catheter-guided therapy over therapy guided by clinical evaluation and judgment alone. The current guidelines reserve the use of a pulmonary artery catheter for the management of refractory heart failure and select conditions. The pulmonary artery catheter remains a useful instrument in clinical situations when clinical and laboratory assessment alone is insufficient in establishing the diagnosis and pathophysiologic condition, and in guiding effective, safe therapy.

Topics: Atrial Natriuretic Factor; Catheterization, Swan-Ganz; Heart Failure; Hemodynamics; Humans; Length of Stay; Natriuretic Peptide, Brain; Oxygen Consumption; Practice Guidelines as Topic; Prognosis; Randomized Controlled Trials as Topic; Registries

Acutely decompensated congestive heart failure is a major public health problem, with constantly rising prevalence, morbidity, mortality and need for hospitalization in both America and Europe. In 2001, the FDA approved the use of the drug nesiritide, which is a recombinant form of human brain or B-type natriuretic peptide (BNP) for the treatment of acutely decompensated congestive heart failure. In 2005, suspicions arose that nesiritide may worsen renal function and increase the risk of short term mortality when given to patients with acutely decompensated heart failure.. The present study reviews the recent literature with respect to the risk of deterioration in renal function and survival after the use of nesiritide in these patients.. Administration of nesiritide may be considered for the treatment of heart failure and especially in patients with dyspnea at rest or with minimal activity.. Extreme caution is required when using nesiritide in patients with both heart failure and concurrent morbidities such as renal dysfunction.

Topics: Blood Urea Nitrogen; Creatinine; Dyspnea; Heart Failure; Humans; Infusions, Intravenous; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Survival Analysis

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

It is estimated that approximately 50% of the heart failure population has a normal left ventricular ejection fraction, a complex broadly referred to as heart failure with normal left ventricular ejection fraction (HFNEF). While these patients have been considered in epidemiologic studies and clinical trials to represent a single pool of patients, limited more detailed studies indicate that HFNEF patients are a very heterogeneous group, with a number of key pathophysiologic mechanisms. This review summarizes and critically analyzes available data on the pathophysiology of HFNEF, placing it into context with a recently developed diagnostic algorithm. We evaluate the utility of commonly applied echocardiographic measures and biomarkers and integrate mechanistic observations into potential future therapeutic directions.

Topics: Algorithms; Atrial Fibrillation; Biomarkers; Cardiac Pacing, Artificial; Coronary Artery Disease; Diastole; Dyspnea; Echocardiography, Doppler; Exercise; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Stroke Volume; Systole; Ventricular Function, Left

Topics: Algorithms; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Diet; Evidence-Based Medicine; Exercise; Heart Failure; Humans; Hypertension; Natriuretic Agents; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Smoking Cessation; Treatment Outcome; Weight Loss

Acute dyspnea is one of the leading causes of emergency hospitalization of elderly patients. Clinical diagnostic procedures are difficult in this geriatric population. Acute heart failure is the most frequent cause of acute dyspnea in geriatric patients. The use of plasma B natriuretic peptide (BNP) assays in the general population has profoundly improved its medical management. There has also been progress recently for other frequent causes of dyspnea in the elderly, including infection and venous thromboembolic disease. Procalcitonin assays may be useful as a prognostic factor for infectious disease. Nevertheless, the real value of BNP assays in geriatric populations must be clarified by interventional studies.

Topics: Acute Disease; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Dyspnea; Emergencies; Emergency Service, Hospital; Female; Fibrin Fibrinogen Degradation Products; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Patient Admission; Pneumonia; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Thromboembolism; Troponin

B-type natriuretic peptide (BNP) has emerged as a reliable biomarker in patients with congestive heart failure. The mature, biologically active B-type natriuretic peptide, BNP(1-32), is cleaved by corin from the 108 amino acid proBNP. However, in vivo as well as in vitro data demonstrated that this BNP(1-32) might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase IV (DPP IV). DPP IV removes the two amino terminal amino acids (Ser Pro) from BNP(1-32) to produce BNP(3-32), which has been detected in plasma of patients with congestive heart failure. The biological effects of BNP(3-32) remain undetermined. In cultured human cardiomyocytes and fibroblasts, equimolar concentrations of BNP(1-32) and BNP(3-32) both exert similar biological effects, as evidenced by their cGMP (cyclic guanylate monophosphate) generating capacity. However, in a canine model, intravenous BNP(3-32) infusion resulted in less natriuresis, diuresis, and vasodilation compared to intravenous infusion of BNP(1-32). The clinical relevance of these observations might be important for patients in whom the plasma BNP concentrations, measured by commercially available immunoassays, are high. Further studies exploring whether DPP IV inhibitors increase the bioavailability of BNP(1-32), delay the progression of heart failure, and increase the efficacy of exogenous administration of BNP(1-32) in decompensated heart failure are needed.

Topics: Animals; Biomarkers; Dipeptidyl Peptidase 4; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain

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

Interactions of glucose metabolism and chronic heart failure have been confirmed by many epidemiologic studies. The association of HbA1c with an increasing risk of heart failure clearly underlines the connection between both diseases. Coronary artery disease (CAD), hypertension and diabetic cardiomyopathy are long-term complications of diabetes mellitus, resulting in diabetic heart failure. Dysfunction of many regulation systems leads to specific diabetic cardiomyopathy, which has been firstly described by Rubler. A reduction in the cardiac expression of the Na-Ca exchanger pump and SERCA2a protein results in an imbalance in cardiac calcium handling. The overactive renin angiotensin aldosteron system (RAAS) also contributes to the impairment of myocardial function. Hyperlipidaemia, hpyerinsulinaemia and hyperglycaemia directly trigger diabetic cardiomyopathy. Generally chronic heart failure is a clinical diagnosis verified by blood tests like NT-proBNP and cardiac ultrasound. Recommendations on treatment of diabetic heart failure are based on subgroup analysis of the large heart failure trials.

Topics: Animals; Apoptosis; Autonomic Nervous System Diseases; Calcium; Cardiomyopathies; Coronary Disease; Cytokines; Diabetes Complications; Diabetic Neuropathies; Heart Failure; Homeostasis; Humans; Hyperglycemia; Hyperlipidemias; Hypertension; Mitochondria, Heart; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress

Echocardiography and the B-type natriuretic peptides (BNPs) provide powerful incremental assessment of cardiac function, clinical status, and outcome across the spectrum of cardiac disease. There is strong evidence to support their integrated use in the diagnosis and management of cardiovascular disease. Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP may guide more effective use of echocardiography in screening for asymptomatic left ventricular dysfunction; Doppler echocardiography improves the accuracy of heart failure diagnosis in the setting of intermediate BNP or NT-proBNP levels. Combined assessment of peptides and echocardiography provides more powerful stratification of risk across all stages of heart failure, and integrated use of both tests may identify subjects with valvular disease at greatest risk for progression and guide decision-making for timely intervention.

Topics: Animals; Biomarkers; Disease Progression; Echocardiography, Doppler; Heart Failure; Heart Valve Diseases; Humans; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

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

Since the introduction of routine assay for natriuretic peptides, there are a growing number of clinical applications for those new tests. Numerous studies have defined analytical characteristics and clinical interest of NT-proBNP assay. Originally limited to acute heart failure diagnosis in the emergency room, NT-proBNP assay has now a wide number of applications. This literature review presents the "state of art" of this marker, detailing NT-proBNP physiological recent knowledge and its recognized or investigated clinical applications.

Topics: Biomarkers; Heart Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Heart failure afflicts > 5 million patients in the US, with about 550,000 new diagnoses a year. Side effects and increased mortality limit heart failure treatment. Nesiritide is the newest addition to therapeutic options for treatment of acute decompensated heart failure (ADHF). It has been used as single in-patient infusions, multiple out-patient infusions, and perioperatively to improve hemodynamics and promote diuresis. Initially well-received, meta-analyses suggesting increased mortality and renal dysfunction after nesiritide use were published 4 - 5 years after its introduction in the US. These reports prompted new recommendations on nesiritide use by an expert panel.. Critical review of the studies leading to approval of nesiritide and the current recommendations for its use.. Medline search and Pubmed search using nesiritide or natrecor for text word searches.. Nesiritide represents the first drug in a new class designed for treatment of ADHF. In patients with ADHF, nesiritide improves hemodynamic parameters and reduces dyspnea. Questions remain about possible increased mortality and side effects. A continuing study expected to enroll 7000 patients by 2010 has been designed to clarify whether nesiritide reduces mortality, hospital length-of-stay and renal parameters in patients with ADHF.

Topics: Animals; Heart Failure; Humans; Length of Stay; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

The objective of this study was to investigate the association between natriuretic peptides, obesity and related comorbidities. A systematic review of the English language literature from 1996 to 2008 was performed with Pubmed/MEDLINE and the ISI Web of Knowledge. 'Natriuretic peptides', 'atrial natriuretic factor', 'brain natriuretic peptide', 'obesity', 'body mass index', 'lipolysis' and 'adipose tissue' were used as Mesh terms. We also conducted a handle search among the references of the original articles selected. Finally, seventy-five studies were considered eligible for inclusion in the review. Natriuretic peptides are widely known as body homeostasis regulators. Recently, their action as lipolytic agents has been identified. Obese patients, especially those with hypertension and metabolic risk factors, have reduced plasma levels of natriuretic peptides. Whether this precedes or follows obesity and its complications remains undefined. The lipolytic effect of natriuretic peptides indicates that they may be involved in the pathophysiology of obesity. In general, studies with obese patients support paradoxical reduced levels of natriuretic peptides. However, the selection of subjects and classification of obesity and heart failure varied among the reviewed studies, rendering comparison unreliable.

Topics: Adipose Tissue; Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Humans; Lipid Metabolism; Lipolysis; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity

In this review we investigate the role of particulate and soluble guanylate cyclase (pGC and sGC, respectively) pathways in heart failure, and several novel drugs that modify guanylate cyclase. Nesiritide and ularitide/urodilatin are natriuretic peptides with vasodilating, natriuretic and diuretic effects, acting on pGC, whilst cinaciguat (BAY 58-2667) is a novel sGC activator. Cinaciguat has a promising and novel mode of action because it can stimulate cyclic guanosine-3',5'-monophosphate synthesis by targeting sGC in its nitric oxide-insensitive, oxidised ferric (Fe(3+)) or haem-free state. Thus, cinaciguat may also be effective under oxidative stress conditions resulting in oxidised or haem-free sGC refractory to traditional organic nitrate therapies. Preliminary studies of cinaciguat in patients with acute decompensated heart failure show substantial improvements in haemodynamics and symptoms, whilst maintaining renal function.

Topics: Animals; Atrial Natriuretic Factor; Benzoates; Creatinine; Disease Progression; Diuretics; Dose-Response Relationship, Drug; Guanylate Cyclase; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments

To assess the accuracy in diagnosing heart failure of clinical features and potential primary care investigations, and to perform a decision analysis to test the impact of plausible diagnostic strategies on costs and diagnostic yield in the UK health-care setting.. MEDLINE and CINAHL were searched from inception to 7 July 2006. 'Grey literature' databases and conference proceedings were searched and authors of relevant studies contacted for data that could not be extracted from the published papers.. A systematic review of the clinical evidence was carried out according to standard methods. Individual patient data (IPD) analysis was performed on nine studies, and a logistic regression model to predict heart failure was developed on one of the data sets and validated on the other data sets. Cost-effectiveness modelling was based on a decision tree that compared different plausible investigation strategies.. Dyspnoea was the only symptom or sign with high sensitivity (89%), but it had poor specificity (51%). Clinical features with relatively high specificity included history of myocardial infarction (89%), orthopnoea (89%), oedema (72%), elevated jugular venous pressure (70%), cardiomegaly (85%), added heart sounds (99%), lung crepitations (81%) and hepatomegaly (97%). However, the sensitivity of these features was low, ranging from 11% (added heart sounds) to 53% (oedema). Electrocardiography (ECG), B-type natriuretic peptides (BNP) and N-terminal pro-B-type natriuretic peptides (NT-proBNP) all had high sensitivities (89%, 93% and 93% respectively). Chest X-ray was moderately specific (76-83%) but insensitive (67-68%). BNP was more accurate than ECG, with a relative diagnostic odds ratio of ECG/BNP of 0.32 (95% CI 0.12-0.87). There was no difference between the diagnostic accuracy of BNP and NT-proBNP. A model based upon simple clinical features and BNP derived from one data set was found to have good validity when applied to other data sets. A model substituting ECG for BNP was less predictive. From this a simple clinical rule was developed: in a patient presenting with symptoms such as breathlessness in whom heart failure is suspected, refer directly to echocardiography if the patient has a history of myocardial infarction or basal crepitations or is a male with ankle oedema; otherwise, carry out a BNP test and refer for echocardiography depending on the results of the test. On the basis of the cost-effectiveness analysis carried out, such a decision rule is likely to be considered cost-effective to the NHS in terms of cost per additional case detected. The cost-effectiveness analysis further suggested that, if likely benefit to the patient in terms of improved life expectancy is taken into account, the optimum strategy would be to refer all patients with symptoms suggestive of heart failure directly for echocardiography.. The analysis suggests the need for important changes to the NICE recommendations. First, BNP (or NT-proBNP) should be recommended over ECG and, second, some patients should be referred straight for echocardiography without undergoing any preliminary investigation. Future work should include evaluation of the clinical rule described above in clinical practice.

Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Primary Health Care; State Medicine

Heart failure is a complex clinical syndrome that manifests itself with signs and symptoms which are neither sensitive nor specific for the diagnosis of heart failure. Natriuretic peptides and in particular b-type natriuretic peptide (and nt-proBNP) are widely used in clinical practice around the world as a maker of heart failure. BNP is primarily released from the left ventricle in response to pressure and volume overload. The strongest evidence for the use of BNP is to rule in or rule out heart failure as cause of breathlessness in people who present to the emergency room. There is enthusiasm for use of BNP as a marker of heart failure severity as well as a predictor of outcomes in people with heart failure and trials are ongoing. Nesiritide, a recombinant form of BNP is currently being tested as a possible treatment in people with acutely decompensated heart failure.

Topics: Biomarkers; Diagnosis, Differential; Disease Progression; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Risk Factors

Chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure. Individuals with COPD have a 4.5-fold greater risk of developing heart failure than those without. The sensitivity and specificity of clinical judgment in the diagnosis of heart failure in patients with COPD can be enhanced by biological markers such as B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide. Correct interpretation of imaging results (mainly echocardiographic findings) and lung function tests can also help establish the co-occurrence of both conditions. There is little evidence on the management of patients with COPD and heart failure, although treatment of COPD undeniably affects the clinical course of patients with heart failure and viceversa.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Bronchodilator Agents; C-Reactive Protein; Combined Modality Therapy; Contraindications; Drug Interactions; Heart Failure; Heart Function Tests; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Respiration, Artificial; Respiratory Function Tests

The use of natriuretic peptide testing has expanded considerably over the recent years. Thanks to clinical trials that have demonstrated significant benefits associated with testing for B-type natriuretic peptide (BNP) and its amino-terminal pro-peptide (NTproBNP), testing for these peptides is now ubiquitous in modern medicine. This review will focus on the use of NTproBNP in clinical medicine, with a discussion of the biologic significance of NT-proBNP, its proven present uses and potential future applications.

Topics: Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; 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

In patients with acute decompensated heart failure, worsening renal function during conventional decongestive therapy (cardiorenal syndrome) affects prognosis and the initiation of therapies with known benefit in chronic heart failure. Potential strategies for decongestion in patients who develop cardiorenal syndrome include invasive hemodynamic monitoring to guide therapy, use of continuous diuretic infusions, ultrafiltration, or novel therapy with adenosine or vasopressin receptor antagonists. Clinical trials by the National Heart, Lung, and Blood Institute's Heart Failure Network are currently underway to validate such therapies in patients with acute decompensated heart failure with worsening renal function and to establish novel biomarkers for the early identification of patients who develop cardiorenal syndrome.

Topics: Acute Kidney Injury; Cardiotonic Agents; Comorbidity; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Purinergic P1 Receptor Antagonists; Receptors, Vasopressin; Syndrome; Ultrafiltration; Vasodilator Agents

Concomitant cardiac and renal dysfunction has been termed the cardiorenal syndrome (CRS). This clinical condition usually manifests as heart failure with worsening renal function and occurs frequently in the acute care setting. A consistent definition of CRS has not been universally agreed upon, although a recent classification of CRS describes several subtypes depending on the primary organ injured and the chronicity of the injury. CRS may develop in adults and children and is a strong predictor of morbidity and mortality in hospitalized and ambulatory patients. The underlying physiology of CRS is not well understood, creating a significant challenge for clinicians when treating heart failure patients with renal insufficiency. This review summarizes recent data characterizing the incidence, physiology, and management of children who have heart failure and acute kidney injury.

Topics: Acute Kidney Injury; Child; Creatinine; Heart Failure; Humans; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Renal Insufficiency, Chronic; Syndrome

Used as biomarkers of heart failure (HF), BNP and NT-proBNP may be considered as the 'fatal finish line' for all cardiovascular disorders. The incidence of heart failure has increased steadily over the past several decades. High readmission rates for patients with acute decompensated heart failure have led to a search for biomarkers able to predict future clinical outcomes that would facilitate HF patient monitoring and help guide therapy. Molecular biomarkers play an important role in heart failure. From among several promising markers, the family of natriuretic peptides, especially B-type natriuretic peptide (BNP) and NT-proBNP, have been identified as potentially valuable diagnostic and prognostic tools. Not unexpectedly, BNP/NT-proBNP fails to fulfill all the criteria of an ideal biomarker. The development of additional biomarkers will be an important step toward improving diagnosis and treatment of patients with chronic and acute decompensated heart failure.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sex Characteristics; Ventricular Dysfunction, Left

Several studies have demonstrated the usefulness of B-type natriuretic peptide (BNP) dosage in patients referring for acute dyspnea in the emergency department. BNP is strongly associated not only with the evidence but even with the degree of heart failure, and BNP values are particularly increased in the advanced NYHA classes and in patients with poor prognosis. High BNP levels correlate with echocardiographic indexes of left ventricular and right ventricular systolic dysfunction but even better with diastolic dysfunction and degree of left ventricular filling pressure. However, in presence of some clinical confounders, such as obesity, renal insufficiency and anemia, BNP dosage itself cannot be interpretable. Under these circumstances, Doppler echocardiography is able to identify with better accuracy patients affected by heart failure. Algorithms built taking into account clinical and echocardiographic parameters as well as BNP measurements are already available in the guidelines of the European Society of Cardiology on heart failure with normal ejection fraction. They will lead to a better and earlier identification, better risk stratification and management of patients referring for heart failure.

Topics: Biomarkers; Echocardiography, Doppler; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Severity of Illness Index

Heart failure is common, causes major disability and often shortens life. Two UK guidelines advocate the measurement of plasma concentrations of B-type natriuretic peptide (BNP) in diagnosis of chronic heart failure, either in combination with, or as an alternative to, an ECG.1,2 Here we review the evidence for BNP testing in the diagnosis of chronic heart failure, and discuss the implications in terms of availability of the test.

Topics: Age Factors; Biomarkers; Cardiovascular Agents; Cost-Benefit Analysis; Exercise; Heart Failure; Humans; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Practice Guidelines as Topic; Sensitivity and Specificity; Sex Factors; Sodium, Dietary; Specimen Handling

Heart failure (HF) is a highly prevalent complex cardiovascular syndrome, and its clinical presentation is usually associated with ventricular dilatation, decreased contractility and reduced left ventricular ejection fraction (EF). However, in the past two decades studies have demonstrated that many patients with signs and symptoms of HF have normal EF (higher than 50%). The great challenge for doctors lies in the identification of patients presenting heart failure with normal ejection fraction (HFNEF) and this challenge seems to be mainly related to the high complexity of the syndrome and to the lack of a standardized method to confirm or exclude the diagnosis that could be used in the daily clinical practice. Unlike in heart failure with reduced ejection fraction (HFREF) in which one single parameter - EF lower than 50%, is sufficient to confirm the diagnosis of the syndrome, in HFNEF different diastolic indexes have been used to characterize the presence or absence of diastolic dysfunction (DD). The purpose of this review is to show new concepts related to the diastolic function that will help understand the cardiovascular pathophysiology of HFNEF, and to discuss the new guideline of the European Society of Cardiology for the diagnosis and exclusion of HFNEF based on cardiac function indices obtained using tissue Doppler imaging (TDI) and natriuretic peptide determination.

Topics: Aged; Diastole; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Stroke Volume

To conduct a meta-analysis of the effect of levosimendan on B-type natriuretic peptide (BNP) levels and evaluate the therapeutic effect of levosimendan on advanced heart failure.. A meta-analysis was performed on the selected data to analyze the effect of levosimendan on BNP levels.. Levosimendan decreased BNP by a mean of 337.66 [95%CI (-296.30, -379.02)] pg/ml 24 h after the administration, and by 259.92 [95%CI (-195.76, -324.08)] pg/ml at 48 h, and by 123.09 [95%CI(-53.32,-195.86)] pg/ml at 1 week. Levosimendan resulted in improvements of the cardiac function by about 29%, 22%, and 10% at 24 h, 48 h and 1 week after the administration.. Levosimendan produces favorable effects on the cardiac functions and BNP levels.

Topics: Cardiotonic Agents; Heart Failure; Humans; Hydrazones; Natriuretic Peptide, Brain; Pyridazines; Simendan

Anemia is prevalent in patients with heart failure and an independent prognostic sign of poor outcome. The current report is a meta-analysis of published clinical trials assessing the use of erythropoeisis stimulating agents (ESA) in heart failure (HF) patients with anemia.. Literature and Medline search was performed to identify studies with control groups (case-control, cohort or randomized controlled trials) that examined the effect of ESA therapy in patients with HF and anemia.. Seven prospective controlled trials met inclusion criteria (n = 663 subjects). The ESA studied was darbepoetin in 4 trials and erythropoietin in 3 trials. Mean follow up period ranged from 12 to 27 weeks. Compared to placebo ESA therapy was associated with improvement in six cardiovascular parameters assessed by at least three of the analyzed trials, including increase in hemoglobin levels 2.35(95% confidence interval [Cl], 1.76-2.93, P < 0.00001), increase in exercise duration 0.91(95% Cl, 0.08-1.73, P = 0.03), improvement in New York Heart Association functional class -1.46(95% Cl, -2.32 to -0.60, P = 0.0009), improvement in 6-minute walk test 1.42(95% Cl, 0.31-2.54, P = 0.01), decrease in B-type natriuretic peptide -0.54(95% Cl, -1.03 to -0.06, P = 0.03), and improvement in peak oxygen consumption 0.93(95% Cl, 0.52-1.34, P < 0.00001).. In patients with heart failure and anemia, erythropoiesis stimulating agent therapy appears to have a positive effect on several important cardiovascular parameters, compared to control therapy. Large prospective randomized controlled trials are warranted to comprehensively evaluate the potential effects of erythropoiesis stimulating agents on clinical outcomes in heart failure patients with anemia.

Topics: Anemia; Clinical Trials as Topic; Exercise Test; Heart Failure; Hematinics; Hemoglobins; Humans; Natriuretic Peptide, Brain; Oxygen Consumption

Natriuretic peptides (B-type natriuretic peptide [BNP] and N-terminal pro-B-type natriuretic peptide [NT]-proBNP) have been proven to be strong diagnostic and prognostic tools in the assessment of acutely decompensated heart failure. The emergence of BNP/NT-proBNP testing as a standard of care in this setting has helped to reduce healthcare costs, and may decrease adverse clinical outcomes. The use of BNP and NT-proBNP to "guide" treatment of acutely destabilized heart failure has recently grown. We present an overview of the value of BNP/NT-proBNP in the context of acute heart failure management and therapy optimization, and present an algorithm for natriuretic peptide-guided treatment of acutely destabilized heart failure.

Topics: Acute Disease; Algorithms; Critical Pathways; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis

Topics: Biomarkers; Education, Continuing; Heart Failure; Humans; Medical Laboratory Personnel; Natriuretic Peptide, Brain

Cardiomyopathy is an anatomic and pathologic diagnosis associated with muscle or electrical dysfunction of the heart. Cardiomyopathies represent a heterogeneous group of diseases that often lead to progressive heart failure with significant morbidity and mortality. Cardiomyopathies may be primary (i.e., genetic, mixed, or acquired) or secondary (e.g., infiltrative, toxic, inflammatory). Major types include dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although cardiomyopathy is asymptomatic in the early stages, symptoms are the same as those characteristically seen in any type of heart failure and may include shortness of breath, fatigue, cough, orthopnea, paroxysmal nocturnal dyspnea, and edema. Diagnostic studies include B-type natriuretic peptide levels, baseline serum chemistries, electrocardiography, and echocardiography. Treatment is targeted at relieving the symptoms of heart failure and reducing rates of heart failure-related hospitalization and mortality. Treatment options include pharmacotherapy, implantable cardioverter-defibrillators, cardiac resynchronization therapy, and heart transplantation. Recommended lifestyle changes include restricting alcohol consumption, losing weight, exercising, quitting smoking, and eating a low-sodium diet.

Topics: Algorithms; Antihypertensive Agents; Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Risk Reduction Behavior

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

To review the current literature on the use of B-type natriuretic peptide in the diagnosis and management of heart failure.. Literature search of PubMed was performed up to September 2007.. Key words for the literature search were 'heart failure' and 'B-type natriuretic peptide'.. Original papers and review articles related to the use of B-type natriuretic peptide in the diagnosis and management of heart failure.. Heart failure is common in Hong Kong, and is associated with significant morbidity and mortality. Heart failure is often misdiagnosed. B-type natriuretic peptide may be regarded as a quantitative marker of heart failure; its levels have good diagnostic accuracy and can be measured with a rapid and simple bed-side assay and are useful in the assessment of patients with acute dyspnoea. Factors, such as obesity and renal impairment, alter B-type natriuretic peptide levels. Measurement of B-type natriuretic peptide facilitates improved medical outcomes, is cost-effective, and constitutes a good prognostic indicator for death and cardiac events.. Determination of B-type natriuretic peptide levels is useful in the assessment of patients with acute dyspnoea, to exclude or diagnose heart failure, to facilitate improved medical outcomes, and is cost-effective. In addition, it is a good long-term prognostic indicator and can be used to guide heart failure treatment.

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

Natriuretic peptide testing in the form of B-type natriuretic peptide (BNP) or NT-proBNP measurement has revolutionized modern heart failure (HF) diagnostics for those patients with acute symptoms, and promises to have similarly profound effects not only for the earlier recognition of those with HF, but also for the therapy of patients across the entire spectrum of HF. Future efforts are necessary to better understand the complex biology of the natriuretic peptides, to further optimize use of the assays for their measurement, and to gain clarity regarding the appropriate venue for their measurement. The ultimate goal is to recognize more readily and treat the syndrome that is HF, in order to reduce the considerable morbidity and mortality among those so afflicted.

Topics: Algorithms; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Acute decompensated heart failure is the most common cause of hospitalization for patients older than 65 years of age. Although treatment of this condition has improved over the past two decades, the specific approach to patients in the acute setting has not evolved in the same way. A patient facing acute decompensation is experiencing a serious medical condition that is associated with a poor prognosis. In addition, acute decompensated heart failure results in significant costs to the health care system. Significant morbidity and mortality are associated with patients who are readmitted within a year of the first hospitalization. Because of this important problem, further research on improving the prognosis for this condition is warranted. The present article will focus on the risk factors associated with acute decompensation and the importance of this condition, both on prognosis and economics.

Topics: Acute Disease; Age Distribution; Aged; Aged, 80 and over; Canada; Cardiotonic Agents; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Hospital Costs; Hospitalization; Humans; Incidence; Male; Natriuretic Peptide, Brain; Patient Readmission; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Analysis

Nesiritide (Natrecor, Janssen-Ortho Inc, Canada), or recombinant human B-type natriurtic peptide (BNP), is a molecule identical in structure to endogenous BNP-32. This peptide is secreted from cardiac myocytes in response to volume and pressure overload. While high levels of circulating BNP are measured by commercially available assays during acute decompensated heart failure (ADHF), the detection of alternate, potentially more active, but undermeasured forms of BNP needs to be considered.. The present review summarizes the molecular and physiological effects of nesiritide in the setting of hospitalized patients with ADHF. In particular, an overview of the molecular structure and circulating isoforms of BNP is given, followed by a discussion of the vasodilatory, renal, antagonistic neurohormonal, pulmonary, anti-inflammatory and cardiac remodelling effects of recombinant human BNP.. Nesiritide has beneficial effects in the treatment of ADHF that go beyond the traditional goals of reducing pulmonary capillary wedge pressure, preload and afterload, and relieving symptoms of dyspnea. Therefore, the unique pharmacological profile of this medication provides an additional treatment option for Canadian patients with ADHF.

Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Failure; Hemodynamics; Hospitalization; Humans; Male; Molecular Biology; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Survival Rate; Treatment Outcome; Ventricular Remodeling

Nesiritide is an effective therapy in decreasing symptoms and left ventricular filling pressure in patients with acute decompensated heart failure. Health Canada has recently approved this agent for the management of this patient population. The clinical trials to date using nesiritide for the management of decompensated heart failure have been summarized. The clinical experience including indications for use, contraindications, dosage and monitoring has been reviewed. The following should serve as a general guide for the clinical use of nesiritide.

Topics: Acute Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Treatment Outcome

One of the most important comorbidities in heart failure is renal dysfunction. Diminished estimated glomerular filtration rate is a potent predictor of cardiovascular mortality and complications. On the other hand, worsening heart failure or acute decompensated heart failure can accelerate worsening of renal function--the so-called cardiorenal syndrome. Risk factors include hypertension, diabetes, elderly age, and prior history of heart or renal failure. The pathophysiology of the cardiorenal syndrome involves intrarenal hemodynamics, transrenal perfusion pressure and systemic neurohormonal factors. Clinical management of the patient with cardiorenal syndrome includes the challenge of diuretic resistance, which may involve correcting the underlying cause, combination diuretics or diuretic infusions. The key to improved outcome is the optimization of proven heart failure therapies. The use of vasodilator therapy is the current mainstay of treatment. Nesiritide, or recombinant B-type natriuretic peptide, has courted controversy regarding its role in cardiorenal syndrome. However, data are emerging that low doses appear to be renal-protective. Other more recent strategies include ultrafiltration, vasopressin antagonists and adenosine antagonists. All of these newer modalities promise more rapid volume removal, but their ultimate impact on survival or preservation of renal function is unknown at the present time. Because of the complex nature of these patients, and the compromised outcome, it is important that cardiologists, nephrologists and internists all work together toward the common goal of protecting the patient with cardiorenal syndrome, and use the best available evidence for management.

Topics: Canada; Cardiology; Cardiotonic Agents; Combined Modality Therapy; Comorbidity; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Humans; Kidney Function Tests; Male; Natriuretic Peptide, Brain; Prognosis; Renal Dialysis; Renal Insufficiency; Risk Assessment; Severity of Illness Index; Survival Analysis; Syndrome; Treatment Outcome

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presenting to an emergency department (ED) and is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes in direct proportion to wall tension, which lowers renin-angiotensin-aldosterone activation. For the diagnosis of CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in an elderly population, and in patients with renal dysfunction. They might also have a prognostic value. Studies have demonstrated that the use of BNP or NT-proBNP in dyspneic patients early following admission to the ED, reduced the time to discharge and total treatment cost. BNP and NT-proBNP should be available in every ED 24 h a day, because the literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients. The purpose of this review is to indicate recent developments in biomarkers of heart failure and to evaluate their impact on clinical use in the emergency setting.

Topics: Acute Disease; Aged; Biomarkers; Diagnosis, Differential; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Sensitivity and Specificity

Valvular heart disease (VHD) is characterized by an ongoing, inflammatory cellular response which results in a left ventricular hemodynamic stress change in response to valvulopathy. The current inflammatory hypothesis suggests that as the heart valve disease progresses the inflammatory cytokine response is activated causing continuation of deleterious effects on the heart and vasculature. This can lead to progression of heart failure and left ventricular dysfunction. Over the last 10 years, a number of biologically active molecules, termed biomarkers, have been discovered in VHD. These can be used to detect the progression and pathogenesis of heart failure and to assess the severity of inflammation (e.g., C-reactive protein). Brain natriuretic peptide (BNP) can diagnose underlying cardiac systolic and diastolic dysfunction. In high-risk patients BNP is also considered to be a useful tool for assisting in the diagnosis and monitoring the progression of VHD. Patients with symptomatic VHD benefit from aortic valve surgery; however, management in the absence of symptoms remains challenging. While the lack of symptoms can delay aortic valve replacement, unselected premature aortic valve replacement may be associated with unbalanced risks of cardiac surgery. This review summarizes the current and emerging clinical and potential research application of specific biomarkers of VHD.

Topics: Biomarkers; C-Reactive Protein; Disease Progression; Heart Failure; Heart Valve Diseases; Humans; Inflammation; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

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

Chronic heart failure poses an enormous health care burden to the United States and other developed countries. Acute decompensated heart failure (ADHF) accounts for nearly half of the morbidity and expense of treating this disease. Most patients presenting with ADHF have symptomatic vascular congestion. Diuretics, especially loop diuretics, are the primary pharmacologic intervention used in this population. Despite their widespread use, scant data from randomized clinical trials are available to guide therapeutic choices. In addition, data from several large registries examining weight loss during hospitalization for ADHF suggest that efficacy with diuretic treatment is far from universal. Aggressive diuresis carries a significant risk of electrolyte and volume depletion, with subsequent arrhythmias, hypotension, and worsening renal function. These complications often translate into worse prognosis. Diuretic regimens used to treat ADHF must be individualized based on general knowledge of potency and pharmacokinetic and pharmacodynamic considerations. This article summarizes older and more recent literature to provide a framework for making rational treatment choices in this difficult patient population.

Topics: Acute Disease; Antidiuretic Hormone Receptor Antagonists; Diuretics; Drug Resistance; Drug Therapy, Combination; Furosemide; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuresis; Natriuretic Agents; Natriuretic Peptide, Brain; Nitrates; Purinergic P1 Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Syndrome; Ultrafiltration; Vasoconstriction

The concept of the heart as an endocrine organ has been attractive since the discovery of atrial natriuretic peptide. This review focuses on the second discovered natriuretic peptide from the heart - B-type natriuretic peptide (BNP), widely used as a tool in the diagnosis of heart failure (HF). Controversy remains regarding its use as a therapeutic agent in HF. This article places into perspective some of the debate and provides insights into the therapeutics of BNP and the importance of its second messenger 3'5' cyclic guanosine monophosphate, which also is the second messenger for nitric oxide and is modulated by renal phosphodiesterases.

Topics: Cyclic GMP; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain

Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: 1) NP levels are quantitative plasma biomarkers of heart failure (HF). 2) NP levels are accurate in the diagnosis of HF. 3) NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge. 4) NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea. 5) NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients. 6) NP levels at discharge aid in risk stratification of the HF patient. 7) NP-guided therapy may improve morbidity and/or mortality in chronic HF. 8) The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF. 9) NP levels can accelerate accurate diagnosis of heart failure presenting in primary care. 10) NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.

Topics: Algorithms; Biomarkers; Comorbidity; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Practice Guidelines as Topic

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

Acutely decompensated heart failure (ADHF) represents an episodic failure of cardiorenal homeostasis that may resolve with upregulation of natriuretic peptides, bradykinin, and certain prostacyclins. B-type natriuretic peptide (BNP) has multiple favorable effects, including vasodilation, diuresis, natriuresis, and inhibition of vascular endothelial proliferation and cardiac fibrosis. By antagonizing the effects of activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in volume overload, the endogenous BNP response may help rescue patients from episodic ADHF. Although knowledge of BNP physiology is expanding, we still have limited understanding of the heterogeneity of proBNP-derived molecules, including active 32 amino acid BNP and less active junk BNP forms. Emerging evidence suggests that in ADHF, the endogenous BNP response is overwhelmed by neurohormonal activation. This relative BNP deficiency may also be accompanied by physiologic resistance to BNP. Additionally, abnormalities of BNP production may result in a lower proportion of active BNP relative to less active forms that may also be detected by point-of-care tests. Improved detection of the various BNP species may clarify these concepts and facilitate improved clinical management of ADHF.

Topics: Cardiovascular Physiological Phenomena; Cardiovascular System; Heart Failure; Humans; Natriuretic Peptide, Brain; Renin-Angiotensin System; Sympathetic Nervous System

B-type natriuretic peptides are quantitative markers of heart failure (and/or cardiac stress) that summarize the extent of systolic and diastolic left ventricular dysfunction, valvular dysfunction, and right ventricular dysfunction. Based on the observation that heart failure is common albeit difficult to diagnose in the ICU, several studies have begun to evaluate the potential use of B-type natriuretic peptides in various ICU settings.. Previous pilot studies have examined the use of B-type natriuretic peptide in the differential diagnosis of hypoxemic respiratory failure, to differentiate cardiogenic from noncardiogenic shocks or to predict fluid responsiveness, to assess myocardial dysfunction and prognosis in patients with severe sepsis, and to predict ventilatory weaning failure.. Although previous studies were small, they highlight the potential of using B-type natriuretic peptides as a noninvasive easily available tool to quantify cardiac stress.

Topics: Biomarkers; Heart Failure; Humans; Intensive Care Units; Natriuretic Peptide, Brain

The evaluation of cardiac endocrine function by means of automated robust assays has permitted the introduction of a cheap and powerful clinical tool. Plasma concentration of B-type-related natriuretic peptides is a marker of either hemodynamic or neurohormonal stress on the heart and has been validated within the diagnostic and prognostic domain in patients with suspected or ascertained heart failure, mostly in the in-hospital setting. Evidence is growing, supporting an out-of-hospital use, namely in primary care. Its implementation in this setting in screening programs and diagnostic algorithms might contribute to decrease the apparent disparity between the general practitioner and the specialist approach to disease management.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Ventricular Dysfunction, Left

B-natriuretic peptide (BNP) and aminoterminal proBNP (NT-proBNP) are clinically useful for the diagnosis of decompensated heart failure and for prognosis in heart failure and acute coronary syndromes. Clinical use of these biomarkers in critically ill patients being treated in intensive care is not well established.. This is a narrative review of evidence identified searching MEDLINE with the strategy [(BNP OR NT-proBNP) AND (critical illness AND intensive care)]. Seven primary reports and two narrative reviews were retrieved. For completeness, literature from each of the following searches was reviewed: [(BNP OR NT-proBNP) AND (critical illness)] and [(BNP OR NT-proBNP) AND (intensive care)].. Primary literature used BNP and NT-proBNP for diagnosis, prognosis and monitoring. For diagnosis of acute lung injury in unselected intensive care patients and for diagnosis of heart failure in trauma patients, the biomarkers had low sensitivity and are of modest use. BNP and NT-proBNP were found to have a significant ability to prognosticate adverse outcomes in critically ill patients. A single paper examined the use of BNP as a non-invasive replacement for pulmonary capillary wedge pressure, finding little value. The impact of renal insufficiency on the markers was noted as a confounder in most studies. In the secondary searches, some preliminary data suggested a possible role for the natriuretic peptides in exclusion of a cardiac cause for certain conditions among intensive care unit (ICU) patients. However, the general findings were that the performance of BNP and NT-proBNP is unimpressive among ICU patients.. Currently, utilization of BNP and NT-proBNP does not appear to provide much useful information or have a substantial role in the care of critically ill patients in intensive care.

Topics: Acute Lung Injury; Adult; Critical Care; Critical Illness; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency; Wounds and Injuries

Despite innovative medications and devices, heart failure (HF) continues to be the leading cause for admission to hospitals in the United States in patients older than 65 years. Many trials have succeeded in improving survival and many have failed. In this article, the authors briefly review the past, describe the present, and speculate about future HF trials.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiotonic Agents; Diuretics; Heart Failure; Hemofiltration; Humans; Hydrazones; Natriuretic Peptide, Brain; Pacemaker, Artificial; Pyridazines; Simendan; Tolvaptan; Vasodilator Agents

Acute decompensated heart failure (ADHF) is a growing public health problem with high mortality and costs. ADHF often, if not usually, occurs in the setting of cardiovascular and noncardiovascular comorbidities as well as advanced age. New insights provide support for the concept of heart failure as a state of deficiency of and/or resistance to endogenous B-type natriuretic peptide. The primary goals of ADHF therapy are to relieve symptoms and optimize volume status with minimal side effects. Few therapies are proven to effectively do so. Nesiritide is a balanced vasodilator with favorable neurohumoral effects and is superior to placebo in providing rapid symptom relief and to nitroglycerin in reducing filling pressures. Recent trials confirm a lack of renal toxicity at recommended doses. An adequately powered multinational mortality trial is underway. Nesiritide represents a proven therapy for normotensive/hypertensive ADHF patients with severe symptoms at rest.

Topics: Acute Disease; Antihypertensive Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Costs; Heart Failure; Humans; Hypertension; Kidney; Natriuretic Peptide, Brain; Patient Selection; Risk Assessment; Treatment Outcome; Vasodilator Agents

Cardiac B-type natriuretic peptides (NPs) are products of a complex neuro-hormonal equilibrium also involving heart and kidneys; they should be carefully handled as heart failure (HF) markers. Meta-analysis of variance (ANOVA) could extrapolate heterogeneity factors (HeFs) in an attempt to reliably evaluate the outcome.. A total of 98 samples from 67 studies were considered - 52 samples from 41 studies evaluating brain natriuretic peptide (BNP), 46 from 24 evaluating N-terminal pro-brain natriuretic peptide (NT-proBNP). Case-control apparently unbiased studies linking NP values to a specific degree of HF clinical severity (HFd), and considering marker sensitivity and specificity, were selected. As an outcome measurement, the natural logarithm of [(true positives/false negatives)/(false positives/true negatives)] was considered. On data negative to the distribution normality and to the publication bias tests, the random-effect heterogeneity test was applied; heterogeneous data - adjusted for the candidate HeFs - were tested using the one-way meta-ANOVA. Afterwards, contrast tests among level means were carried out on the HeFs significant to the one-way meta-ANOVA and not significant to the interaction two-way meta-ANOVA tests. A sensitivity analysis was carried out on the data without the outlier results.. Reference method (RM), disease prevalence (DP) and HFd resulted in significant BNP HeFs, RM and DP being responsible for, respectively, reference and spectrum biases. No significant NT-proBNP HeFs were found.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Acutely dyspneic patients are challenging, because their symptoms can be due to cardiac, pulmonary or other diseases. B-type natriuretic peptide testing offers higher diagnostic accuracy (85%-90%) than clinical assessments for identifying heart failure as the cause of dyspnea. On the other hand, the high clinical sensitivity and negative predictive value of natriuretic peptides permit to rule out heart failure with an accuracy > 90%. Natriuretic peptides are the most powerful, single prognostic markers of complications associated with acute dyspnea and permit the early recognition of high-risk patients. It has been shown that systematic natriuretic peptide testing reduces the economic expenses associated with clinical management of acutely dyspneic patients. Finally, whether these biomarkers could be used to guide heart failure therapy in the acute setting remains to be elucidated.

Topics: Clinical Chemistry Tests; Cost-Benefit Analysis; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis

Acute decompensated heart failure (ADHF) has emerged as a major healthcare problem. It causes approximately 3% of all hospitalizations in the United States, with the direct medical cost of these hospitalizations estimated at $18.8 billion per year. Early recognition, risk stratification, and evidence-based treatment are crucial in reducing the morbidity, mortality, and costs associated with this disorder. Classic signs and symptoms of ADHF, such as rales, dyspnea, and peripheral edema, may be absent at hospital presentation and, even when present, are not specific to this disorder. As a result, serum B-type natriuretic peptide level is now used to rapidly and accurately detect ADHF. Multivariate analyses have identified renal dysfunction, hypotension, advanced age, hyponatremia, and comorbidities as significant and independent mortality risk factors. Based on these factors, mortality risk can be stratified from very low to very high using published algorithms that have been validated in independent populations. Evidence-based guidelines for the treatment of ADHF are available from both the European Society of Cardiology and the Heart Failure Society of America. In general, an intravenous loop diuretic, either alone or in combination with a vasodilator, is recommended as initial therapy in patients with volume overload, depending on the patient's clinical status. Use of inotropic agents should be limited to the small subset of patients with low-output syndrome and significant hypotension. In any event, frequent monitoring of clinical response is essential, with subsequent therapy determined by this response. Finally, focused patient education during hospitalization may help reduce readmissions for ADHF.

Topics: Acute Disease; Algorithms; Biomarkers; Clinical Competence; Continuity of Patient Care; Evidence-Based Medicine; Heart Failure; Hospitalists; Humans; Natriuretic Peptide, Brain; Patient Care Management; Practice Guidelines as Topic; Risk Assessment

With advances in cardiovascular medicine, people are living longer with cardiovascular disease. There is an increased incidence and prevalence of heart failure. Misdiagnosis of heart failure, particularly in the early stages, is not uncommon. Natriuretic peptides (BNP and NT-proBNP) have been established to be of additional value to the clinical examination in heart failure diagnosis and management. As frontline caregivers for heart failure patients, nurses should be aware of the clinical use of these peptides either as a complementary diagnostic test for heart failure or as a possible therapeutic modality.

Topics: Biomarkers; Canada; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

As a result of population ageing and improved medical care that contribute to better life expectancy, heart failure occurs more and more commonly in the elderly. In the USA approximately 80% of patients discharged from hospital with newly diagnosed heart failure are over 65 years of age, whereas 50% are over 75. The average 5-year mortality rate is about 50% in subjects with systolic dysfunction and similar in those with preserved left ventricular systolic function. Disorders of the cardiovascular system occurring in the elderly (e.g. increased left ventricular mass, myocardial rigidity, atrial fibrillation, decreased maximum oxygen uptake in cardiopulmonary exercise tests) result from the physiological ageing; they may also be caused by a concomitant cardiac failure syndrome. In the elderly, heart failure is often accompanied by concomitant conditions that often make diagnosis and treatment of chronic heart disease difficult. Non-specific clinical symptoms in the elderly as well as those associated with age (e.g. easy fatigability, exertional dyspnea) make a correct diagnosis difficult. The recognized biochemical marker of heart failure--brain natriuretic peptide, N-terminal pro-brain natriuretic peptide--has a limited diagnostic value in the elderly. Echocardiography plays a key role in the diagnosis. Owing to altered metabolism, impairment of hepatic processes to various degrees and decreased renal excretion of drugs, treatment requires attention, individual choice of drugs and doses, as well as periodic modification of both the doses and the intervals between them. Correct treatment improves quality of life and prolongs it. The aim of the present work is to present the differences in the pathophysiology, diagnostic evaluation and management of chronic heart failure in the elderly, in light of the current views and standards.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Atrial Natriuretic Factor; Electrocardiography; Geriatric Assessment; Health Services for the Aged; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Poland; Prognosis; Quality of Life; Risk Factors; Ultrasonography; Ventricular Dysfunction, Left

We sought to compare the diagnostic performance of B-type natriuretic peptide (BNP) and N-terminal proBNP measurements in patients presenting to acute care settings with dyspnea, a common presenting symptom of heart failure.. We conducted a systematic review of the literature. For all included studies, we applied the QUADAS 14-question quality assessment tool for systematic reviews of diagnostic accuracy and abstracted the data for every published cut point.. We screened 4338 studies and included nine in the meta-analysis. All 9 studies scored positively on at least 50% of the QUADAS questions. The pooled estimates of sensitivity and specificity were the same for the BNP studies (0.97 (95% CI: 0.96, 0.98) and 0.70 (95% CI: 0.56, 0.85)) as for the NT-proBNP studies (0.95 (95% CI: 0.90, 1.01) and 0.72 (95% CI: 0.53, 0.90)). Tests for heterogeneity were significant in both subgroups: BNP (I(2)=97.9%, p<0.001) and NT-proBNP (I(2)=87.5%, p<0.001). Similar overall results were found for the likelihood and diagnostic odds ratios.. BNP and NT-proBNP have very similar diagnostic performance characteristics and can be used to rule out heart failure as a cause of dyspnea in the acute clinical setting. However, there is no easily identifiable optimum cut point value for each peptide.

Topics: Dyspnea; Emergency Medical Services; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity

To determine the screening and diagnostic properties of BNP and NT-proBNP for heart failure in primary care.. We conducted a systematic review of randomized control trials and observational (cohort or case-control) studies of heart failure detection using B-type natriuretic peptides published in English from January 1989 to February 2005. We extracted or calculated sensitivity, specificity, positive and negative likelihood ratios, area under the receiver-operator characteristic curve and diagnostic odds ratio (DOR).. We included 17 studies (7 screening, 9 diagnosis in primary care or specialised clinic, 1 both). There was considerable heterogeneity within the study populations, reference standard for diagnosis, and B-type natriuretic peptide decision point. Sensitivity ranged from 26% to 98%; and specificity from 44% to 88%. For screening, the Diagnostic Odds Ratio (DOR) ranged from 2.7 to 29, and for diagnosis from 2.8 to 137.. The performance characteristics of B-type natriuretic peptides measurement are not suitable for screening asymptomatic patients. For diagnosis in primary care, low B-type natriuretic peptide values may be used to rule-out heart failure but, due to poor specificity, high values cannot be used to rule-in the condition.

Topics: Case-Control Studies; Cohort Studies; Databases, Factual; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic

Establishing a diagnosis of heart failure in elderly patients is notoriously difficult, especially in those who experience slowly progressive breathlessness, have multiple co-morbidity, and when, as in primary care echocardiography is not routinely (or readily) available. B-type natriuretic peptides measurements are useful in the diagnostic assessment of such patients, although the evidence in the very old (i.e. those aged 75 years and over) is less clear than for younger patients. Conflicting results in literature regarding B-type natriuretic peptides are mainly caused by differences in assays, the applied 'gold standard' for heart failure, and the population studied. Moreover, there is no consensus as to whether similar cut-off points should be applied across age-groups. Numerous studies showed that plasma levels of B-type natriuretic peptide are elevated in the elderly, including the 'healthy' ones. Age-related myocardial fibrosis and subtle diastolic dysfunction that are not detectable by current techniques, and reduced renal clearance have been suggested as reasons for this phenomenon. Importantly, B-type natriuretic peptides are not specific for heart failure, but reflect haemodynamic myocardial stress independent of the underlying pathology, and thus are more 'markers' of the general cardiac state. Cut-points differ widely when comparing studies in patients with acute versus chronic dyspnoea. In patients with acute dyspnoea age-dependent cut-points should be used, while in patients with chronic dyspnoea (that is, slowly progressive breathlessness) at least thresholds below which heart failure can be excluded seem rather independent of age. Especially in the primary care setting where elderly patients with slowly progressive dyspnoea are investigated, the excellent exclusionary capacities of B-type natriuretic peptides are of great help to select those that require echocardiography to establish or eventually reject a diagnosis of heart failure.

Topics: Age Factors; Aged; Aged, 80 and over; Biological Assay; Heart Failure; Humans; Natriuretic Peptide, Brain

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

Circulating concentrations of B-type natriuretic peptide (BNP) and the aminoterminal fragment (NT-proBNP) of its prohormone (proBNP) are increased in congestive heart failure in proportion to the severity of symptoms, the degree of left ventricular dysfunction, and cardiac filling pressures. Following the introduction of rapid, automated assays for determination of BNP and NT-proBNP, these peptides are increasingly used for diagnostic and prognostic purposes.. To review studies evaluating the diagnostic and prognostic value of BNP and NT-proBNP, with special emphasis on their performance as indicators of acute heart failure in the intensive care unit.. In patients presenting with acute dyspnea, both BNP and NT-proBNP are accurate indicators of acute heart failure and provide prognostic information above and beyond conventional risk markers. Increased plasma levels of BNP and NT-proBNP are not specific for heart failure and may be influenced by a variety of cardiac and noncardiac conditions commonly seen in the intensive care unit, including myocardial ischemia, cardiac arrhythmias, sepsis, shock, anemia, renal failure, hypoxia, acute pulmonary embolism, pulmonary hypertension, and acute respiratory distress syndrome.. The diagnostic performance of BNP and NT-proBNP as indicators of acute heart failure depends on the clinical setting. In the intensive care unit, particular caution should be used in the interpretation of elevated BNP and NT-proBNP levels.

Topics: Acute Disease; Biomarkers; Dyspnea; Heart Failure; Humans; Intensive Care Units; Lung Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Sepsis

Heart failure is one of the leading causes of hospitalizations in the United States. Concomitant and significant renal dysfunction is common in patients with heart failure. Increasingly, the syndrome of heart failure is one of cardiorenal failure, in which concomitant cardiac and renal dysfunctions exist, with each accelerating the progression of the other. One fourth of patients hospitalized for the treatment of acute decompensated heart failure will experience significant worsening of renal function, which is associated with worse outcomes. It remains unclear whether worsening renal function specifically contributes to poor outcomes or whether it is merely a marker of advanced cardiac and renal dysfunction. Diuretic resistance, with or without worsening renal function, is also common in acute decompensated heart failure, although the definition of diuretic resistance, its prevalence, and prognostic implications are less well defined. The term cardiorenal syndrome has been variably associated with cardiorenal failure, worsening renal function, and diuretic resistance but is more comprehensively defined as a state of advanced cardiorenal dysregulation manifest by one or all of these specific features. The pathophysiology of the cardiorenal syndrome is poorly understood and likely involves interrelated hemodynamic and neurohormonal mechanisms. When conventional therapy for acute decompensated heart failure fails, mechanical fluid removal via ultrafiltration, hemofiltration, or hemodialysis may be needed for refractory volume overload. While ultrafiltration can address diuretic resistance, whether ultrafiltration prevents worsening renal function or improves outcomes in patients with cardiorenal syndrome remains unclear. Evidence regarding the potential renal-preserving effects of nesiritide is mixed, and further studies on the efficacy and safety of different doses of nesiritide in heart failure therapy are warranted. Newer therapeutic agents, including vasopressin antagonists and adenosine antagonists, hold promise for the future, and clinical trials of these agents are underway.

Topics: Acute Disease; Adenosine; Cardiotonic Agents; Dopamine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Ultrafiltration; Vasopressins

Recent guidelines by the Heart Failure Society of America have recommended consideration for use of nitroprusside, nitroglycerin, or nesiritide in addition to diuretics to achieve hemodynamic and symptomatic improvement. This article reviews the results of previous studies evaluating the pharmacologic and clinical effects and safety profiles of these drugs in patients with heart failure.

Topics: Acute Disease; Coronary Circulation; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Kidney; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Nitrates; Nitroprusside; Vasodilator Agents

In contrast to their established role in the evaluation of acute dyspnea in emergency department (ED) patients, applications of B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) in patients outside of the ED are less well defined. A PubMed-based electronic and hand search for articles dealing with BNP and NT-proBNP in settings other than the ED was performed. We found that currently available evidence is sufficient to support the use of BNP and NT-proBNP in four cardiovascular settings outside of the ED: i) evaluation of patients with suspected heart failure (HF) referred from primary care, ii) risk stratification in patients with HF, iii) risk stratification in stable coronary artery disease, and iv) risk stratification in pulmonary artery hypertension. Recent studies indicate that BNP and NT-proBNP might also be helpful in guiding therapy in patients with chronic HF. Despite active research in many additional fields, the use of BNP/NT-proBNP in other settings is not yet based on solid evidence and, therefore, seems not to be useful.

Topics: Biomarkers; Coronary Disease; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

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

When used for the evaluation of patients with acute symptoms in the emergency department setting, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing is highly sensitive and specific for the diagnosis or exclusion of acute destabilized heart failure (HF), with results comparable to those reported for B-type natriuretic peptide (BNP) testing. When used for the diagnostic evaluation of the patient with possible HF, NT-proBNP testing returns information that may be superior to clinical judgment. However, the optimal application of NT-proBNP is in concert with history and physical examination, adjunctive testing, and with the knowledge of the differential diagnosis of an elevated NT-proBNP level. Studies indicate a dual use for NT-proBNP, both to exclude acute HF (where NT-proBNP concentrations <300 ng/L have a 98% negative predictive value), as well as to identify the diagnosis. To identify acute HF in patients with dyspnea, an age-independent NT-proBNP cut point of 900 ng/L has a similar value as that reported for a BNP value of 100 ng/L. However, age stratification of NT-proBNP using cut points of 450, 900, and 1,800 ng/L (for age groups of <50, 50-75, and >75 years) reduces false-negative findings in younger patients, reduces false-positive findings in older patients, and improves the overall positive predictive value of the marker without a change in overall sensitivity or specificity. Clinically validated, cost-effective algorithms for the use of NT-proBNP testing exist. Therefore, the logical use of NT-proBNP for the evaluation of the patient with suspected acute HF is useful, cost-effective, and may reduce adverse outcomes compared with standard clinical evaluation without natriuretic peptide testing.

Topics: Acute Disease; Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Recurrence; Sensitivity and Specificity

When used for the evaluation of symptomatic patients in general practice, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing is highly sensitive, with an excellent negative predictive value for cost-effective exclusion of the diagnosis of heart failure (HF). Importantly (similar to other NP assays), lower values for NT-proBNP are expected among patients with HF in the primary care setting compared with patients with acute dyspnea. Among primary care patients with dyspnea, a noncardiac source of dyspnea is most likely in patients with findings below the recommended age-stratified NT-proBNP cut points. Conversely, an NT-proBNP result above the age-stratified primary care cut points does not absolutely indicate the presence of HF; a more directed cardiovascular workup is indicated.

Topics: Biomarkers; Diagnosis, Differential; Diagnostic Techniques, Cardiovascular; Heart Failure; Humans; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Primary Health Care; Prognosis; Protein Precursors; Severity of Illness Index

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) values between the cut point of 300 ng/L for "ruling out" acute heart failure (HF) and the consensus-recommended age-adjusted cut points for "ruling in" acute HF are referred to as intermediate or gray zone values, which may be seen in approximately 20% of patients with dyspnea in the emergency department. Knowledge of the differential diagnosis of the causes of a gray zone NT-proBNP finding is useful to ascertain the correct diagnosis. Possible causes include cardiac ischemia, atrial fibrillation, and infectious/inflammatory pulmonary diseases. Importantly, a gray zone NT-proBNP result is not associated with a benign prognosis. Regardless of the cause, it should not be ignored because it is a "negative" result. Patients with a gray zone NT-proBNP value are at higher risk for hazard compared with those with a negative NT-proBNP result.

Topics: Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index

Although amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are useful for the diagnosis or exclusion of heart failure (HF), this marker may identify a wide range of disease processes other than HF. Indeed, elevation of NT-proBNP may occur in a number of heart diseases (including heart muscle disease, valve disease, rhythm abnormalities, pulmonary hypertension, and cytotoxic injury to the heart) and in disease processes other than primary cardiac illnesses, including gram-negative sepsis. Importantly, although NT-proBNP may increase in settings other than HF, the presence and severity of such NT-proBNP release is often significantly associated with risk for adverse outcome. Accordingly, elevation of NT-proBNP in the context of non-HF situations should not be regarded as a "false-positive" finding, and elevated NT-proBNP values should not be discarded without consideration of the serious adverse outcomes associated with the elevation. Future studies will be necessary to further understand the utility of NT-proBNP testing in states other than cardiovascular disease.

Topics: Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index

In patients with chronic heart failure (HF), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are among the strongest independent predictors of hazard, and their measurement is useful for prognostication across the entire spectrum of HF disease severity. In patients with chronic HF, repeated determinations of NT-proBNP levels appear to convey additional prognostic value for relevant adverse outcomes, including death or HF hospitalization. Although "hard targets" for NT-proBNP values are not entirely defined, morbidity and mortality in chronic HF appear to increase markedly with an NT-proBNP concentration >1,000 ng/L. Confounding factors (such as renal function or obesity) should be kept in mind when prognostically evaluating patients using NT-proBNP measurements; however, the value of NT-proBNP is retained in these patients. Thus, serial assessment of NT-proBNP is valuable for prognostication in chronic HF in outpatients, and, as such, a measurement at each patient visit or the following of changes in clinical stability is recommended.

Topics: Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index

In patients presenting with acute dyspnea of any cause, elevation of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) is powerfully prognostic for adverse outcomes, including death. Among those with acute destabilized heart failure (HF), an NT-proBNP cut point of approximately 5,000 ng/L is powerfully predictive of death by 76 days after presentation. For 1-year risk stratification, an NT-proBNP value of approximately 1,000 ng/L at presentation is optimal. Among those patients with elevated NT-proBNP levels, a posttreatment NT-proBNP value may be of even greater value than the presenting value. Although NT-proBNP is powerfully prognostic in patients with acute dyspnea with and without HF, the addition of clinical variables strengthens the ability to discriminate risk. In addition, multimarker approaches, including NT-proBNP, for the assessment of acute dyspnea or acute HF appear promising. Indeed, when combined with conventional markers, such as measures of renal dysfunction, anemia, myocardial injury, or inflammation, the predictive value of NT-proBNP is considerably strengthened. Given the strong value of NT-proBNP for risk assessment of the patient with acute dyspnea, a baseline measurement for all patients with dyspnea is recommended, with pretreatment and posttreatment measurement of NT-proBNP recommended for patients with an elevated value, especially those with HF.

Topics: Acute Disease; Biomarkers; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong and independent prognostic marker in patients across the spectrum of heart failure (HF) stages, including patients managed in the outpatient setting. Serial measures of NT-proBNP are more valuable than single measures for prognosis, and biologic variation of the marker should allow serial monitoring. Furthermore, given that NT-proBNP levels decrease in response to the addition of therapies with proven benefit for HF (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, spironolactone, exercise therapy, and biventricular pacing), it is logical to expect that targeting therapy to decrease NT-proBNP levels may facilitate more optimal use of proven HF therapies and may reduce adverse clinical outcomes. The optimal strategy for NT-proBNP monitoring with regard to frequency of testing or whether to use standard or individualized targets is still being determined. Preliminary results are promising for targeting an outpatient NT-proBNP concentration of approximately < or =1,000 ng/L. Current data suggest that when NT-proBNP levels are not at goal or increase from prior measurements, the risk for hazard is increased. Adjustments in treatment and serial clinical follow-up with NT-proBNP retesting should be considered at frequent intervals until biochemical stabilization or achievement of a maximally tolerated medical program.

Topics: Ambulatory Care; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Practice Guidelines as Topic; Prognosis; Protein Precursors

Although typically elevated at presentation in the context of destabilized heart failure (HF), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) values typically decrease rapidly among patients who have a favorable response to therapy. Given this, it is natural to examine the relation between NT-proBNP and therapeutic interventions for acute HF. Both presentation and posttreatment NT-proBNP concentrations have some value for prognostication of recurrent HF hospitalization or death. However, the percent change in NT-proBNP after treatment for acute HF may be a more powerful method for risk stratification. Although prospective studies on the effect of NT-proBNP measurement in guiding therapy in acute destabilized HF are lacking, observational data suggest that a 30% decrease in NT-proBNP values during hospitalization is a reasonable goal. If a baseline measure of NT-proBNP is not available, an NT-proBNP level <4,000 ng/L after acute treatment is an alternative goal. Because the criteria for determining restabilization from destabilized HF prominently include clinical and routine laboratory testing rather than NP measures, the frequency of NT-proBNP measurement should not be excessive in patients with acute HF, with measures at baseline/presentation and after perceived recompensation to evaluate for the desired decrease in NT-proBNP concentrations. A remeasurement of NT-proBNP may also be useful for evaluation of new or worsened symptoms. In those patients without a decrease in NT-proBNP despite perceived recompensation from HF, a review of adequacy of treatment, goals of therapy, and consideration of prognosis is recommended.

Topics: Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Inpatients; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Prognosis; Protein Precursors; Severity of Illness Index

Concentrations of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are often markedly elevated immediately after birth and typically decrease to normal concentrations after the first week of life. Despite these early life elevations (which likely reflect activity of the natriuretic peptide system to assist in mobilization of fluid in the neonatal period), NT-proBNP has been shown to be useful for the diagnosis or exclusion of heart failure (HF) in the neonate, infant, adolescent, and older child. After the resolution of the normative early-life elevations of NT-proBNP, it is reasonable to use age-adjusted cut points suggested for younger adults (<50 years), namely levels <300 ng/L to "rule out" HF, and >450 ng/L to "rule in" HF. In children with congenital heart disease with or without symptoms of HF, NT-proBNP concentrations are typically elevated and may be prognostically useful. Furthermore, NT-proBNP may be useful for the identification of patients treated with cardiotoxic chemotherapy at risk for the subsequent development of cardiomyopathy. Knowledge of expected concentrations of NT-proBNP at varying stages of life is important to optimally utilize this assay in the pediatrics setting.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Heart Failure; Humans; Infant; Infant, Newborn; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors

Several therapies commonly used for the treatment of acute heart failure syndromes (AHFS) present some well-known limitations and have been associated with an early increase in the risk of death. There is, therefore, an unmet need for new pharmacologic agents for the early management of AHFS that may improve both short- and long-term outcomes.. To review the recent evidence on emerging pharmacologic therapies in AHFS.. A systematic search of peer-reviewed publications was performed on MEDLINE, EMBASE and Clinical Trials.gov from January 1990 to August 2007. The results of unpublished or ongoing trials were obtained from presentations at national and international meetings and pharmaceutical industry releases. Bibliographies from these references were also reviewed, as were additional articles identified by content experts.. Cumulative data from large studies and randomised trials suggest that therapies with innovative mechanisms of action may safely and effectively reduce pulmonary congestion or improve cardiac performance in AHFS patients.. Some investigational agents for the management of AHFS are able to improve haemodynamics and/or clinical status. In spite of these promising findings, no new agent has demonstrated a clear benefit in terms of long-term clinical outcomes compared to placebo or conventional therapies.

Topics: Adenosine; Cardiovascular Agents; Endothelin-1; Etiocholanolone; Heart Failure; Hemodynamics; Humans; Hydrazones; Natriuretic Peptide, Brain; Perhexiline; Pyridazines; Randomized Controlled Trials as Topic; Simendan; Sodium-Potassium-Exchanging ATPase; Syndrome; Vasodilator Agents

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

Recent literature on the role of biomarkers in heart failure is reviewed, focusing on B-type natriuretic peptide.. Knowledge of the processes which increase ventricular stress, thus increasing B-type natriuretic peptide, is key to appropriate utilization and interpretation of B-type natriuretic peptide levels. B-type natriuretic peptide is a useful adjunct to confirm or rule out heart failure. B-type natriuretic peptide is a robust prognostic indicator in all stages of heart failure, with prognostic significance in patients undergoing cardiac and noncardiac surgery, and in those with acute coronary syndromes. Serial B-type natriuretic peptide testing predicts outcomes in hospitalized patients with heart failure. The role of B-type natriuretic peptide in screening high-risk populations is promising, but its use in unselected populations is unclear. There is increasing evidence that the use of B-type natriuretic peptide to guide heart failure management is associated with improved clinical outcomes and reduced health costs.. Biomarkers play an important role in heart failure, but there remain unanswered questions regarding optimization of their use. They should be used as an adjunct to, not replacement for, clinical assessment. Currently available B-type natriuretic peptide assays have limitations relating to clinical variability and assay specificity. Other neurohormonal, inflammatory and metabolic markers may add complementary information to that provided by currently available B-type natriuretic peptide assays.

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

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Continuity of Patient Care; Diuretics; Emergency Nursing; Emergency Treatment; Heart Failure; Humans; Male; Monitoring, Physiologic; Natriuretic Agents; Natriuretic Peptide, Brain; Nurse Practitioners; Nurse's Role; Point-of-Care Systems; Practice Guidelines as Topic; Pulmonary Wedge Pressure; Severity of Illness Index; Triage; United States

Circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment (NT) of its prohormone (proBNP) are related to cardiac function and have emerged as clinically useful tools for the diagnosis of heart failure and for the estimation of prognosis in patients with heart failure and acute coronary syndromes. Recent studies have also convincingly documented that both BNP and NT-proBNP are powerful, independent prognostic indicators in patients with stable coronary artery disease. The associations are strongest for the end-points of death and heart failure, whereas the association with cardiac ischemic events is weaker or nonexistent, after adjustment for confounding factors. Importantly, BNP and NT-proBNP appear to provide incremental prognostic information to conventional risk factors, including markers of ventricular function and ischemia. Data documenting that BNP or NT-proBNP measurements can be used to guide treatment decisions in patients with stable coronary artery disease are still lacking.

Topics: Acute Coronary Syndrome; Biomarkers; Coronary Artery Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Protein Precursors; Risk 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

The widespread use of brain natriuretic peptide testing among patients with end-stage kidney disease (ESKD) has brought new insight to prognostic cardiovascular factors in this population, but has also raised questions regarding the diagnostic potential of B-type natriuretic peptide (BNP) and NT-proBNP in subjects with renal impairment.. Highlighting the most important recent observations in the field, this review discusses the unique characteristics of BNP testing and interpretation in chronic kidney disease.. We review in detail the physiology and effects of BNP along with providing a thoughtful analysis of the limitations of BNP testing in patients with impaired kidney function. Additionally, the practicability of BNP in the management of renal patients with some rational suggestions for the use of BNP are presented.. Although at present the use and interpretation of BNP testing in ESKD patients is complicated by altered renal clearance and frequent cardiac co-morbidity and, moreover, the complex and in many parts unknown interplay between the heart and the kidneys (cardiorenal syndrome), the prognostic value of elevated BNP is validated in the ESKD population. The importance of improving our understanding of the mechanisms of biomarkers in heart-kidney interdependence is emphasized.

Topics: Biomarkers; Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Unrecognized chronic heart failure is present in 21-30% of chronic obstructive pulmonary disease patients. It may be a precipitating factor for acute exacerbation of chronic obstructive pulmonary disease or may hinder weaning from mechanical ventilation. The aim of the review is to emphasize recent studies that validated measurements of plasma B-type natriuretic peptide in the diagnosis of heart dysfunction in chronic obstructive pulmonary disease patients.. Measurements of B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptides are accurate in the diagnosis of left heart dysfunction in chronic obstructive pulmonary disease patients either in stable condition or during acute exacerbation of chronic obstructive pulmonary disease. Natriuretic peptide thresholds are elevated in comparison to cut-offs usually reported in patients without pulmonary disease. B-type natriuretic peptide dosage is also able to uncover new onset of left heart failure associated with weaning difficulties from mechanical ventilation in chronic obstructive pulmonary disease patients.. Recent evidence suggests that natriuretic peptide measurements are accurate in the diagnosis of coexisting left heart failure in chronic obstructive pulmonary disease patients, either in stable condition or during severe cardiopulmonary interactions occurring during acute exacerbation of chronic obstructive pulmonary disease, or evoking weaning difficulties related to left heart dysfunction.

Topics: Acute Disease; Blood Volume Determination; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive

Prospective, randomized clinical trials are the gold standard for establishing cause-and-effect relationships between therapeutic interventions and specific outcomes. Unfortunately, these types of studies are not always available to evaluate important clinical end points such as mortality. Meta-analyses and observational studies are often used in an attempt to fill the gap in the literature when no prospective, randomized trials exist to answer a research question. A rapid increase in the number of published meta-analyses and observational studies has occurred in recent years. In the absence of prospective, randomized studies, it is essential for the clinician to understand the important issues involved in interpreting these other types of studies. When evaluating a meta-analysis, the clinician should assess for several different forms of bias, clinical heterogeneity, and use of appropriate methodology. When evaluating an observational study, sources of bias and confounding should be identified. If the potential for confounding is present, the methods used to minimize the impact of confounders should be evaluated for appropriateness. Mortality associated with nesiritide in the treatment of acute decompensated heart failure is a contemporary example of the use of nonrandomized research to address a research question that is unanswered by prospective, randomized studies. We review the details of a recent meta-analysis and observational evaluation of mortality associated with nesiritide and discuss the issues that are important in critical evaluation of nonrandomized study designs.

Topics: Bias; Clinical Trials as Topic; Confounding Factors, Epidemiologic; Heart Failure; Humans; Meta-Analysis as Topic; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Research Design; Retrospective Studies

Topics: Acute Disease; Critical Care; Critical Illness; Diagnosis, Differential; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Respiratory Distress Syndrome; Ventilator Weaning

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

The treatment of acute decompensated heart failure (ADHF) remains a therapeutic challenge. Nesiritide was approved by the FDA in 2001 for the treatment of patients with ADHF who have dyspnea at rest or with minimal exertion. Although widely adopted for the treatment of ADHF due to its ability to decrease ventricular filling pressures and to provide mild symptomatic benefit, recent analyses have suggested that nesiritide worsens renal function and increases mortality. Although some discount these analyses that demonstrate the potential dangers of nesiritide, others have stated that its use at the present time must be weighed against the possibility of worse outcomes. A large outcomes trial in patients with ADHF would help clarify the role of nesiritide.

Topics: Animals; Heart Failure; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Risk Factors

B-type natriuretic peptide (BNP) and NTproBNP have been shown to be extremely helpful in the diagnosis and management of patients with heart failure (HF). These neurohormones are predominately secreted from the left and the right cardiac ventricle in response to volume and pressure overload. BNP and NT-proBNP can be seen as quantitative markers of HF summarizing the extent of systolic and diastolic left ventricular dysfunction. Research data from clinical studies and six years of clinical experience with BNP allow us to provide clear recommendations regarding the integration of BNP/NT-proBNP into clinical medicine. With multiple additional indications in prospect, current evidence clearly supports the use of BNP and NT-proBNP in three clinical settings: patients with acute dyspnoea, prior to discharge in patients hospitalised with acute HF, and the longterm management of patients with HF.

Topics: Biomarkers; Cost-Benefit Analysis; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

There are conflicting data on the usefulness of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the optimization of therapy for heart failure (HF). Discordant results may be explained by the intra-individual variability of these peptides. This study evaluates the intraindividual variability of BNP and NT-proBNP and the impact of the covariates of age, sex, and renal function.. Stable HF patients attending our unit were included. Blood samples were drawn 1 hour apart on 2 occasions 1 week apart. Forty-five patients were enrolled (69.6 +/- 12.1 years, 64% male, 84% systolic HF). Within-hour and within-week intraindividual variability were: 6.9% and 21.1% for NT-proBNP; 14.6% and 28.4% for BNP (P < .01 for within-hour comparison of BNP and NT-proBNP). Reference change values over 1 week for NT-proBNP and BNP were 49.2% and 66.2%, respectively. There were no significant relationships identified between variability and age, gender, or glomerular filtration rate.. There is considerable intraindividual variability in these peptides in stable HF patients. Changes of approximately 50% and 66% for NT-proBNP and BNP from week to week are needed to indicate an altered clinical status and caution should be exercised in interpreting serial changes in these peptide levels when monitoring patient responses to treatment or clinical status.

Topics: Age Factors; Aged; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Sex Factors

Biomarkers have gained increasing significance in clinical cardiology during the last two decades. Laboratory parameters play an important role as risk markers for coronary events in primary and secondary prevention, in the diagnosis of acute myocardial necrosis and heart failure as well as in the management of patients with heart valve diseases. The development of novel biochemical markers has also led to new insights in the pathophysiology of coronary artery disease, acute coronary syndromes and heart failure. This review summarizes the state of the art of cardiac biomarkers suitable for routine use.

Topics: Biomarkers; C-Reactive Protein; Coronary Disease; Heart Diseases; Heart Failure; Heart Valve Diseases; Homocysteine; Humans; Lipoprotein(a); Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Troponin

B-Type natriuretic peptide (BNP) is elevated in states of increased ventricular wall stress. BNP is most commonly used to rule out congestive heart failure (CHF) in dyspneic patients. BNP levels are influenced by age, gender and, to a surprisingly large extent, by body mass index (BMI). In addition, it can be elevated in a wide variety of clinical settings with or without CHF. BNP is elevated in other cardiac disease states such as the acute coronary syndromes, diastolic dysfunction, atrial fibrillation (AF), amyloidosis, restrictive cardiomyopathy (RCM), and valvular heart disease. BNP is elevated in non-cardiac diseases such as pulmonary hypertension, chronic obstructive pulmonary disease, pulmonary embolism, and renal failure. BNP is also elevated in the setting of critical illness such as in acute decompensated CHF (ADHF) and sepsis. This variation across clinical settings has significant implications given the increasing frequency with which BNP testing is being performed. It is important for clinicians to understand how to appropriately interpret BNP in light of the comorbidities of individual patients to maximize its clinical utility. We will review the molecular biology and physiology of natriuretic peptides as well as the relevant literature on the utilization of BNP in CHF as well as in other important clinical situations, conditions that are commonly associated with CHF and or dyspnea.

Topics: Animals; Biomarkers; Comorbidity; Critical Illness; Dyspnea; Heart Diseases; Heart Failure; Humans; Lung Diseases; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency; Sensitivity and Specificity

In 1628, Harvey first correctly described the heart as a pump. It was another 350 years before the heart was established as an endocrine gland that synthesized a family of peptide hormones that regulate blood volume and blood pressure. There are now five peptide hormones made in the heart which have been demonstrated to have beneficial effects in persons with congestive heart failure. One of these peptide hormones i.e. brain natriuretic peptide (BNP) is commercially available and has been widely used in the United States for the treatment of acute congestive heart failure under the name Nesiritide/Natrecor. Nesiritide has one serious side effect, i.e. it may worsen renal function in persons with acute decompensated cardiac failure. The best of these peptide hormones for the treatment of chronic heart failure is a cardiac hormone named vessel dilator which enhances sodium and water excretion 4- to 5-fold in persons with congestive heart failure but vessel dilator's biologic effects lasts six hours compared to less than 30 minutes for BNP, without the deleterious effects of BNP on renal function. This review will focus on six cardiac hormones' discovery, identification and comparison of their beneficial effects and side effects in humans with congestive heart failure.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Physiological Phenomena; Heart Failure; Hormones; Humans; Mice; Mice, Knockout; Mice, Transgenic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type

Acute decompensated heart failure (ADHF) is an important milestone in the clinical course of heart failure (HF). It is an event associated with a significant deterioration in the prognosis of HF. Despite the progress that has been made in the development of new pharmacologic and nonpharmacologic therapy for HF, there is surprisingly limited advancement in the treatment of acute HF. There are currently no guidelines for the treatment of ADHF. This is a review of the current diagnostic evaluation and treatment of patients with ADHF.

Topics: Aged; Biomarkers; Clinical Trials as Topic; Defibrillators, Implantable; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Prognosis; Pulmonary Edema

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

Congestive heart failure (CHF) is an increasingly common medical condition and the fastest growing cardiovascular diagnosis in North America. Over one-third of patients with heart failure also have renal insufficiency. It has been shown that renal insufficiency confers worsened outcomes to patients with heart failure. However, a majority of the larger and therapy-defining heart failure medication and device trials exclude patients with advanced renal dysfunction. These studies also infrequently perform subgroup analyses based on the degree of renal dysfunction. The lack of information on heart failure patients who have renal insufficiency likely contributes to their being prescribed mortality and morbidity reducing medications and receiving diagnostic and therapeutic procedures at lower rates than heart failure patients with normal renal function. Inclusion of patients with renal insufficiency in heart failure studies and published guidelines for medication, device, and interventional therapies would likely improve patient outcomes.

Topics: Acute Disease; Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Cardiac Pacing, Artificial; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Milrinone; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Treatment Outcome; Ultrafiltration

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

Topics: Acute Disease; Administrative Personnel; Adult; Biomarkers; Diuretics; Emergency Medicine; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Peptide, Brain; Positive-Pressure Respiration; Syndrome; Treatment Outcome; Vasodilator Agents

Predicting which patients with congestive heart failure will decompensate is often difficult, and it is often difficult to distinguish congestive heart failure from other causes of acute dyspnea. This review will focus on some of the newer tools used to diagnose acute congestive heart failure in addition to reviewing the utility of more traditional tools.. The integration of pertinent positives and negatives on a routine history, key physical findings on examination and routine noninvasive imaging offers high positive and negative predictive power for the diagnosis of acute heart failure. Measurement of B-type natriuretic peptide and N-terminal proB-type natriuretic peptide offers additional and incremental diagnostic information. Measurement of intrathoracic impedance is a novel and potentially useful tool to track absolute changes in cardiac function and total lung fluid content, and may be useful for the outpatient titration of medical therapy to minimize acute congestive heart failure decompensation.. Consistent accurate diagnosis of decompensated congestive heart failure is possible using no more than a complete history and physical examination along with routine imaging techniques. The ability to diagnose acute congestive heart failure however, is improved by using serum B-type natriuretic peptide and intrathoracic impedance, both of which offer additive and complementary diagnostic information.

Topics: Acute Disease; Cardiac Pacing, Artificial; Cardiography, Impedance; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain

Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.

Topics: Atrial Natriuretic Factor; Cardiovascular Agents; Clinical Trials as Topic; Cyclic GMP; Drug Therapy, Combination; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Peptide Fragments; Receptors, Atrial Natriuretic Factor; Snake Venoms; Treatment Outcome

Most patients with acute heart failure present with increased left ventricular filling pressure and high or normal blood pressure; only a minority present with cardiogenic shock. In this context, therapy with vasodilators in the acute setting can improve both hemodynamics and symptoms. Vasodilators are usually given in conjunction with diuretics, although much of the acute effect of loop diuretics may be due to venodilation. Currently available agents include nitroglycerin, nitroprusside, and nesiritide. Nitroglycerin relieves pulmonary congestion primarily through direct venodilation, but may dilate coronary arteries and increase collateral blood flow at higher doses, an effect desirable in patients with ischemia. Tachyphylaxis may develop, necessitating incremental dosing. The major adverse effects of nitrates are hypotension and headache. Nitroprusside is a balanced arterial and venous vasodilator with a very short half-life, facilitating rapid titration. Afterload reduction lowers blood pressure and can increase stroke volume. The major complications of nitroprusside therapy are hypotension, and toxicity from accumulation of cyanide or thiocyanate, usually in patients with renal insufficiency treated for more than 24 h. Nesiritide, a recombinant form of human B-type natriuretic peptide (BNP), is a venous and arterial vasodilator that may also potentiate the effect of concomitant diuretics. Hypotension is the most common side effect. In addition, meta-analyses have suggested that nesiritide may worsen renal function and decrease survival at 30 days compared to conventional therapies. Resolution of these concerns awaits completion of appropriately powered prospective clinical trials. Angiotensin-converting enzyme (ACE) inhibitors have vasodilatory effects, but intravenous infusion of enalapril within 24 h of ischemic chest pain is not recommended. Oral ACE inhibition may be used to reduce afterload in other settings if blood pressure permits. Use of calcium antagonists in acute heart failure is not recommended.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Treatment Outcome; Vasodilator Agents

Acute decompensated heart failure poses a complex clinical challenge for the health care community. Evolving concepts of the pathophysiology and lack of consensus on appropriate outcome measures for drug approval underlie some of the current controversies about nesiritide. We outline the major controversies from the viewpoint that nesiritide should continue to be used judiciously by following its package insert recommendations and the Heart Failure Society of America's 2006 Comprehensive Heart Failure Practice Guidelines.

Topics: Acute Disease; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Patient Selection; Practice Guidelines as Topic; Renal Insufficiency

The use of nesiritide for acute decompensated heart failure (ADHF) has been clouded with controversy since its approval in 2001. Extensive marketing and many review articles have established this drug as a safe and superior product to current standards. However, its safety has been called into question by the results of a meta-analysis, and its superiority of important outcomes (length of stay, mortality, decreased readmission rate) has never been proved by a randomized trial against agents with similar vasodilator properties (e.g., nitroglycerin). A review of the available literature on nesiritide in the areas of mortality, renal effects, retrospective studies, use in off-label indications, length of stay, and mortality is presented and illustrates why its use should be limited or even eliminated. After review of this article, the reader should be able to answer the question--if nesiritide had never been approved for use in patients with ADHF, would we have missed it?--with a negative reply.

Topics: Acute Disease; Drug Labeling; Heart Failure; Humans; Length of Stay; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Readmission; Practice Guidelines as Topic; Renal Insufficiency; Research Design

Congestive heart failure is increasing in prevalence in the United States, and associated morbidity and mortality remain high. Aggressive treatment of decompensated heart failure is associated with improved outcomes; however, therapies must be tailored to the presenting characteristics of each patient and most carry a risk of adverse events stemming from the pharmaceutical itself. Nesiritide is approved for the treatment of acutely decompensated heart failure, but aggregate data analysis has suggested that it may be associated with a risk of excess mortality and worsening renal insufficiency. We review the recent evidence regarding the efficacy and safety profile of nesiritide, and discuss upcoming trials designed to address concerns regarding safety and the comparative efficacy of nesiritide.

Topics: Acute Disease; Animals; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Treatment Outcome

Nesiritide is US Food and Drug Administration-approved for the treatment of patients with acutely decompensated heart failure who suffer from symptoms at rest or with minimal exertion. Its approval was based on a clinical development program that focused on surrogates and short-term effects on symptoms rather than clinical outcomes. The association between its use and subsequent risk of death raises the question of whether the endpoints assessed in the clinical development program were adequate, and provides the opportunity to evaluate the process of weighing risks with benefits. We conclude that with nesiritide, the risks of therapy outweigh the benefits demonstrated to date.

Topics: Acute Disease; Animals; Biomarkers; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors

Acute heart failure (HF) is characterized by the rapid onset or progression of symptoms and signs secondary to abnormal cardiac function, and remains a common disease associated with high morbidity and mortality rates. Angiotensin-converting enzyme inhibitors (ACEi) are an effective pharmacological option in the treatment of chronic HF, but their effect in acute HF is less well known. This review attempts to summarize the current understanding of acute HF and the pharmacological effects of ACEi in the treatment of acute HF.

Topics: Acute Disease; Administration, Sublingual; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Captopril; Drug Therapy, Combination; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Pulmonary Edema; Treatment Outcome; Vasodilator Agents

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides

Topics: Biomarkers; Heart Failure; Natriuretic Peptide, Brain; Prognosis

Topics: Clinical Laboratory Techniques; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Biomarkers; Creatine Kinase; Heart Failure; Humans; Myoglobin; Natriuretic Peptide, Brain; Point-of-Care Systems; Troponin I

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

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

Congestive heart failure (CHF) affects millions of Americans and is responsible for the highest number of annual hospital admissions (Braunwald, 2005). Recent developments have occurred regarding clinical markers used in diagnosing CHF, including plasma B-type natriuretic peptide (BNP). In this article, the pathophysiology of plasma BNP in the CHF patient, indications for its use, benefits, and factors that can affect plasma BNP levels are explored.

Topics: Aged; Arthroplasty, Replacement, Hip; Bias; Biomarkers; Centrifugation; Cost-Benefit Analysis; Diagnosis, Differential; Female; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain; Nurse's Role; Nursing Assessment; Patient Selection; Reference Values; Risk Factors; Sensitivity and Specificity

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

Topics: Blood Pressure; Calcium; Cardiotonic Agents; Clinical Trials as Topic; Cytokines; Heart Failure; Heart Rate; Humans; Hydrazones; Inflammation Mediators; Natriuretic Peptide, Brain; Pyridazines; Shock, Cardiogenic; Simendan

Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Diagnostic Imaging; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis

Topics: Antihypertensive Agents; Biomarkers; Blood Pressure Monitoring, Ambulatory; Echocardiography; Electrocardiography; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Life Style; Natriuretic Peptide, Brain; Prognosis; Ventricular Function, Left

Brain natriuretic peptide (BNP) is one of the cardiac peptide hormones that are involved in water and electrolyte homeostasis in heart failure. There are two mechanisms for increased BNP gene expression: cardiomyocyte stretching and neurohormonal activation. Many recent studies reported an increase in BNP gene expression with elevated plasma concentrations of BNP/NT-proBNP and its precursor, proBNP, in overt heart failure as well as in myocardial ischemia or acute coronary syndrome. In addition, the elevated plasma concentrations of BNP and NT-proBNP are a prognostic marker of morbidity, mortality and later development of heart failure in patients with acute coronary syndrome. In the management of children with congenital heart disease the role of BNP as a diagnostic tool is less evident. This review summarizes recently known facts about the role of BNP in the diagnosis, management and prognosis of congestive heart failure, myocardial ischemia and congenital heart disease (Ref. 33). Full Text (Free, PDF) www.bmj.sk.

Topics: Biomarkers; Heart Defects, Congenital; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Obesity is associated with an increased risk of heart failure. Apparently healthy obese individuals can, however, exhibit subclinical left ventricular dysfunction. The use of myocardial imaging techniques to detect this subclinical change could have important management implications with respect to initiating prophylactic therapy. In this Review, we evaluate possible pharmacologic and nonpharmacologic strategies for treating obesity cardiomyopathy in the context of currently understood mechanisms, including myocardial remodeling and small vessel disease, and more speculative mechanisms such as insulin resistance, and activation of the renin-angiotensin-aldosterone and sympathetic nervous systems.

Topics: Animals; Anti-Obesity Agents; Bariatric Surgery; Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Ventricular Dysfunction, Left; Weight Loss

Nesiritide is a recombinant form of human B-type natriuretic peptide, a naturally occurring endogenous hormone released by cardiac ventricles in response to an increase in ventricular wall stress. Its use in the treatment of acute decompensated heart failure (ADHF) has been evaluated in a series of randomised controlled clinical trials. It is currently approved in the US for the treatment of ADHF. Nesiritide induces a balanced vasodilation and an indirect increase in cardiac output, but has no actual inotropic effects and exerts a neutral effect on heart rate. In addition, it inhibits adverse neurohormonal activation and, in some individuals, promotes natriuresis and diuresis. In adults with ADHF, nesiritide reduces pulmonary capillary wedge pressure, right atrial pressure and systemic vascular resistance; decreases symptoms of heart failure; and enhances global clinical status. Important questions regarding the risks of nesiritide therapy have recently been raised, and resolution of the safety of nesiritide is a process that remains in evolution. The most frequently reported adverse effect is dose-related hypotension. In addition, nesiritide may cause an acute increase in serum creatinine concentration. This increase seems to be a haemodynamic response to a combination of volume depletion, vasodilation and neurohormonal inhibition. Nesiritide-induced changes in renal function have not been definitively shown to negatively affect mortality. The effect of nesiritide on all-cause mortality is currently unresolved. Recent meta-analyses of existing databases have raised concerns regarding adverse effects of the drug on 30-day mortality. However, reviews of large, observational, registry databases do not suggest an adverse inpatient mortality effect compared with other vasodilator therapies. Further resolution of the mortality question awaits completion of pending randomised controlled clinical trials. When used for approved indications and according to recommended dosage and administration regimens, nesiritide represents a reasonable treatment adjunct for ADHF.

Topics: Acute Disease; Arrhythmias, Cardiac; Heart Failure; Hemodynamics; Humans; Hypotension; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Assessment

Tissue Doppler imaging is an echocardiographic technique that directly measures myocardial velocities. Diastolic tissue Doppler velocities reflect myocardial relaxation, and in combination with conventional Doppler measurements, ratios (transmitral early diastolic velocity/mitral annular early diastolic velocity [E/Ea]) have been developed to noninvasively estimate left ventricular (LV) filling pressure. Consequently, mitral E/Ea can help to establish the presence of clinical congestive heart failure in patients with dyspnea. However, E/Ea has a significant 'gray zone', and is not well validated in nonsinus rhythm and mitral valve disease. B-type natriuretic peptide (BNP) is a protein released by the ventricles in the presence of myocytic stretch, and has been correlated to LV filling pressure and, independently, to other cardiac morphological abnormalities. In addition, BNP is significantly affected by age, sex, renal function and obesity. Given its correlation with multiple cardiac variables, BNP has high sensitivity, but low specificity, for the detection of elevated LV filling pressures. Taking into account the respective strengths and limitations of BNP and mitral E/Ea, algorithms combining them can be used to more accurately estimate LV filling pressures in patients presenting with dyspnea.

Topics: Diastole; Dyspnea; Echocardiography, Doppler; Heart Failure; Humans; Natriuretic Peptide, Brain; Sensitivity and Specificity; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Ventricular Dysfunction, Left

Acute heart failure syndrome (AHFS) is prevalent and costly, and clinical development of pharmacologic therapy remains challenging. Relieving congestion is still the central goal in the decompensated states, although the predominant approach remains the use of intravenous loop diuretics. Newer agents such as vasopressin receptor antagonists have yet to show incremental benefits. A resurgence of interest in vasodilator therapy has been supported by a better understanding of the pathophysiology of AHFS and the availability of nesiritide and other natriuretic peptides, but long-term clinical outcomes data are lacking and highly debated. Several promising drugs are currently undergoing clinical development for the treatment of AHFS, although many of the clinical challenges remain unresolved.

Topics: Antidiuretic Hormone Receptor Antagonists; Catecholamines; Heart Failure; Humans; Hydrazones; Myocardial Contraction; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Pyridazines; Randomized Controlled Trials as Topic; Simendan; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Vasodilator Agents

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

Biologically active B-type natriuretic peptide or brain natriuretic peptide (BNP) and biologically inactive N-terminal proBNP (NT-proBNP) are secreted into the bloodstream by the heart and provide primarily information regarding the filling pressures in the heart. The accuracy of plasma BNP levels in the diagnosis of heart failure is comparable to that of plasma NT-proBNP levels. Reliable assays have been developed for both peptides, some of which can be used for rapid diagnosis in the emergency clinic. In both groups of patients with heart failure and the general population, there is a relationship between the plasma BNP and NT-proBNP levels and the risk of cardiovascular death, after correction for the traditional risk factors. Screening studies using the determination of BNP or NT-proBNP levels in order to detect patients with heart failure at an early stage cannot be recommended because their specificity is too low: in addition to heart failure, the plasma BNP or NT-proBNP level is affected by age, gender, body mass index, renal function, and pulmonary capacity. There are indications that the introduction ofa rapid BNP determination for patients that present to the emergency clinic with acute dyspnoea will lead to more effective diagnosis and treatment. Sequential determinations ofthe plasma BNP or NT-proBNP levels in inpatients and outpatients with heart failure can help to optimise the treatment, thus decreasing the morbidity and mortality that are associated with heart failure.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Sensitivity and Specificity

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Monitoring, Physiologic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism; Pulmonary Wedge Pressure; Renal Dialysis; Stroke; Weight Loss

Natriuretic peptide (NPs) levels have achieved worldwide acceptance. They are excellent rule-in and rule-out biomarkers for patients presenting with dyspnea. In the hospital, NP levels may represent altered forms of B-type natriuretic peptide (BNP), including the inactive precursor molecule, pro-BNP. NP levels drop during hospitalization as the patient is decongested. In the future, NP levels may be used as a surrogate to titrate outpatient therapy.

Topics: Acute Coronary Syndrome; Acute Disease; Algorithms; Biomarkers; Dyspnea; Heart Failure; Humans; Kidney Diseases, Cystic; Monitoring, Ambulatory; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism

Although diuretics remain the most commonly used intravenous medication for acute decompensated heart failure, vasoactive agents play an important role in select patient populations. Inotropes and pressor agents are critical in order to maintain blood pressure and cardiac output in a small subset of patients, and can preserve and even improve renal function. However, they should not be used in the majority of patients with preserved cardiac output. Vasodilators improve hemodynamics and symptoms in normotensive individuals. Their influence on renal function is less clear cut, although more recent data suggest a neutral effect.

Topics: Acute Disease; Cardiac Output; Cardiotonic Agents; Heart Failure; Hemodynamics; Humans; Kidney; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Nitrates; Sympathomimetics; Vasodilator Agents

Acute decompensated heart failure (ADHF) represents the most common discharge diagnosis in patients over age 65, and has an exceptionally high mortality and read-mission risk. ADHF is characterized by abnormal hemodynamics, including increase in pulmonary capillary wedge pressure and peripheral vasoconstriction, although cardiac index may be reduced, normal, or increased. Myocardial injury, which may be related to decreased coronary perfusion, activation of neurohormones, and/or renal dysfunction, may contribute to short-term and postdischarge cardiovascular events. Recent ADHF registries have provided valuable insights into the characteristics, treatment patterns, and clinical outcomes of these patients. Most patients with ADHF present with either normal systolic blood pressure or elevated blood pressures; hypotension is relatively uncommon. These patients have significant cardiovascular and noncardiovascular comorbidities that may contribute to the pathogenesis and/or adverse outcomes in ADHF. Therapies for ADHF have been targeted to improve symptoms and hemodynamics, as well as preserve or improve renal function, prevent myocardial damage, modulate neurohumoral and inflammatory activation, and manage other comorbidities that may cause and/or contribute to the progression of this syndrome. Concomitant therapies proven to provide long-term benefits in chronic heart failure are also essential. There remains an unmet need for therapeutic approaches for the early management of ADHF that may improve short- and long-term outcomes. Ongoing clinical trials are intended to provide data that will better define the benefits and risks of therapies for ADHF.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Coronary Disease; Heart Failure; Hospital Mortality; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Assessment

On account of universality and steadily rising frequency of atrial fibrillation new diagnostic and therapeutic methods of that arrhythmia are being sought. This work informs about a predictive role of measurement of C-reactive protein (CRP) and brain natriuretic peptide (BNP)ry concentrations in atrial fibrillation. The presented review of current research in the field of the above mentioned subject shows that high values of CRP quite tightly correlate with the risk of occurrence or relapse of that arrhythmia. Therapy effectiveness of atrial fibrillation is also lower in case of patients with high CRP concentration. Measurement of BNP is currently used, above all, in the diagnosis of heart failure. The work presents the arguments which can justify the usage of measurement of that hormone at above all prognostic proceedings in case of patients with various forms of atrial fibrillation.

Topics: Atrial Fibrillation; C-Reactive Protein; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Recurrence

In this chapter, we discuss the fundamental principles behind two of the most frequently used statistical inference procedures: confidence interval estimation and hypothesis testing, both procedures are constructed on the sampling distributions that we have learned in previous chapters. To better understand these inference procedures, we focus on the logic of statistical decision making and the role that experimental data play in the decision process. Numerical examples are used to illustrate the implementation of the discussed procedures. This chapter also introduces some of the most important concepts associated with confidence interval estimation and hypothesis testing, including P values, significance level, power, sample size, and two types of errors. We conclude the chapter with a brief discussion on statistical and practical significance of test results.

Topics: Confidence Intervals; Data Interpretation, Statistical; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prostate-Specific Antigen; Prostatic Neoplasms

Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating from recent work that ANP and BNP exert their cardioprotective functions not only as circulating hormones but also as local autocrine and/or paracrine factors. In studies using cultured neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP antagonists demonstrated that ANP has antihypertrophic and antifibrotic functions. Corroborating these in vitro results, mice lacking natriuretic receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and fibrosis independent of their blood pressure. Recent studies also suggest that the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role against the intracardiac renin-angiotensin-aldosterone system and TGF-beta mediated pathway. In a clinical setting, human recombinant ANP and BNP may be used for a therapy of heart failure; however, further evaluation is required in the future.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Heart Failure; Humans; Mice; Mice, Knockout; Models, Animal; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Receptors, Atrial Natriuretic Factor; Renin-Angiotensin System; Signal Transduction

Experience with amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing for evaluation of dyspnoeic patients with suspected acute heart failure (HF) is limited to single-centre studies. We wished to establish broader standards for NT-proBNP testing in a study involving four sites in three continents.. Differences in NT-proBNP levels among 1256 patients with and without acute HF and the relationship between NT-proBNP levels and HF symptoms were examined. Optimal cut-points for diagnosis and prognosis were identified and verified using bootstrapping and multi-variable logistic regression techniques. Seven hundred and twenty subjects (57.3%) had acute HF, whose median NT-proBNP was considerably higher than those without (4639 vs. 108 pg/mL, P<0.001), and levels of NT-proBNP correlated with HF symptom severity (P=0.008). An optimal strategy to identify acute HF was to use age-related cut-points of 450, 900, and 1800 pg/mL for ages <50, 50-75, and >75, which yielded 90% sensitivity and 84% specificity for acute HF. An age-independent cut-point of 300 pg/mL had 98% negative predictive value to exclude acute HF. Among those with acute HF, a presenting NT-proBNP concentration >5180 pg/mL was strongly predictive of death by 76 days [odds ratio=5.2, 95% confidence interval (CI)=2.2-8.1, P<0.001].. In this multi-centre, international study, NT-proBNP testing was valuable for diagnostic evaluation and short-term prognosis estimation in dyspnoeic subjects with suspected or confirmed acute HF and should establish broader standards for use of the NT-proBNP in dyspnoeic patients.

Topics: Acute Disease; Clinical Trials as Topic; Dyspnea; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; ROC Curve; Stroke Volume

The discovery of cardiac natriuretic hormones required a profound revision of the concept of heart function. The heart should no longer be considered only as a pump but rather as a multifunctional and interactive organ that is part of a complex network and active component of the integrated systems of the body. In this review, we first consider the cross-talk between endocrine and contractile function of the heart. Then, based on the existing literature, we propose the hypothesis that cardiac endocrine function is an essential component of the integrated systems of the body and thus plays a pivotal role in fluid, electrolyte, and hemodynamic homeostasis. We highlight those studies indicating how alterations in cardiac endocrine function can better explain the pathophysiology of cardiovascular diseases and, in particular of heart failure, in which several target organs develop a resistance to the biological action of cardiac natriuretic peptides. Finally, we emphasize the concept that a complete knowledge of the cardiac endocrine function and of its relation with other neurohormonal regulatory systems of the body is crucial to correctly interpret changes in circulating natriuretic hormones, especially the brain natriuretic peptide.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Heart Failure; Homeostasis; Humans; Molecular Sequence Data; Myocardial Contraction; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor

Topics: Algorithms; Blood Pressure; Cardiac Output; Cardiotonic Agents; Critical Care; Decision Trees; Diuretics; Drug Monitoring; Heart Failure; Humans; Illinois; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Nurse's Role; Patient Selection; Severity of Illness Index; Treatment Outcome; Vasodilator Agents; Ventricular Pressure

Natriuretic peptides (NP) are essential in mammals to regulate blood volume and pressure. The functional roles of NP are not limited to natriuresis and diuresis. Several peripheral and central actions of the peptides have been characterized. Studies on transgenic mice have revealed their key function in the regulation of cardiomyocyte growth. Plasma NP levels increase in patients with cardiovascular disorders and heart failure. They represent useful clinical markers for clinicians to diagnose heart diseases. The recent discovery of their potent lipolytic action in adipose tissue is a breakthrough in cardiovascular medicine. This new function of NP in the regulation of lipid metabolism offers interesting questions in the field of obesity, diabetes and cardiovascular diseases. This review will briefly describe the effects of NP on the cardiovascular system and lipid metabolism.

Topics: Adipose Tissue; Animals; Biomarkers; Cardiovascular System; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Kidney; Lipid Metabolism; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Receptors, Atrial Natriuretic Factor; Signal Transduction

The role of natriuretic peptides in pathogenesis of chronic heart failure (CHF) is reviewed. Main attention is given to significance of measurement of brain natriuretic peptide in the following clinical situations related to CHF: diagnosis of CHF, screening of patients with symptomless left ventricular dysfunction, differential diagnosis of edematous syndrome, indications to therapy and monitoring of its effectiveness, assessment of long term prognosis of patients with CHF. Possibilities of curative use of natriuretic peptides and inhibitors of vasopeptidases are also discussed.

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

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels can indicate a variety of heart problems, as well as general critical illness. BNP and NT-proBNP assays are useful for evaluating patients with acute dyspnea, as a low level of natriuretic peptide can help rule out congestive heart failure (CHF) and reduce reliance on echocardiography. Conversely, these assays can be particularly useful in recognizing CHF in a patient with acute dyspnea and a history of chronic obstructive pulmonary disease. However, clinical judgment must always be part of the evaluation of BNP or NT-proBNP assay results.

Topics: Diagnosis, Differential; Dyspnea; Electrocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Physical Examination; Prognosis; Pulmonary Disease, Chronic Obstructive; Radiography, Thoracic

Topics: Aged; Aortic Valve Stenosis; Blood Gas Analysis; Cardiotonic Agents; Diagnosis, Differential; Female; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Lymphoma, Non-Hodgkin; Natriuretic Peptide, Brain; Nurse Practitioners; Nurse's Role; Nursing Assessment; Oncology Nursing; Oxygen Inhalation Therapy; Risk Factors; Vasodilator Agents

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126 amino acid atrial natriuretic peptide (ANP), 108 amino acid B-type natriuretic peptide (BNP) and 103 amino acid C-type natriuretic peptide (CNP) prohormones). The ANP prohormone contains four peptide hormones: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide and ANP. 2. Currently, the only natriuretic peptide available commercially to treat congestive heart failure (CHF) is BNP (Nesiritide/Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post-nesiritide treatment, a finding that needs further investigation. 3. The best of the natriuretic peptides for treating chronic CHF is the vessel dilator, which increases urinary flow up to 13-fold and sodium excretion up to fourfold, without the previously mentioned side-effects. The natriuretic and diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF. 4. Atrial natriuretic peptide does not cause significant improvement in acute renal failure (ARF) in humans. The only natriuretic peptide that significantly improves ARF is the vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model, vessel dilator decreases serum creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the vessel dilator. After 6 days of treatment with the vessel dilator, the proximal and distal tubules regenerate. 5. In cancer, vessel dilator, LANP, kaliuretic peptide and ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate adenocarcinoma cells, as well as small cell and squamous cell lung cancer cells within 24 h. In vivo, vessel dilator, LANP and kaliuretic peptide completely stop the growth of human pancreati

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neoplasms; Renal Insufficiency

Severe decompensated congestive heart failure unresponsive to conventional diuretic and vasodilator treatment is a clinical challenge. A new molecule, nesiritide or recombinant human BNP, has been recently successfully marketed in the U.S. due to its attractive physiologic effects. Unfortunately, the safety of nesiritide is now questioned based on two meta-analyses suggesting that nesiritide may be responsible for a worsening of renal function and an increased mortality. In the absence of further large scale studies with relevant endpoints, which are now unlikely to be conducted, nesiritide is rapidly disappearing from the therapeutic armamentarium.

Topics: Heart Failure; Humans; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Circulation; Treatment Failure; United States

Heart failure (HF) and episodes of acute decompensated HF (ADHF) continue to pose a substantial clinical challenge in the United States and represent a significant source of morbidity, mortality, and health care resource use. Recent therapeutic advances have shifted ADHF treatment paradigms from diuretic management with or without inotrope use to therapy where intravenous vasodilators are the central component, above a background of diuretics. This shift in treatment has resulted in more rapid symptomatic improvements as well as in decreases in overall morbidity and mortality. Elevated left ventricular filling pressure has become an important clinical target for resolution during ADHF, as this parameter most closely correlates with degree of symptoms, extent of ischemic complications, and the deleterious neurohormonal activation in response to ADHF. Therapies that lead to rapid improvements in left ventricular filling pressure, including the use of nesiritide, a recombinant analog of B-type natriuretic peptide, have been shown to provide rapid symptomatic relief, but effects on long-term morbidity and mortality are as yet unclear. In addition to new treatments, new technologies--including assays based on cardiac biomarkers and techniques such as impedance cardiography for noninvasive monitoring of hemodynamic parameters--are contributing to improvements in care that will ultimately reduce the sizeable clinical and economic burden that HF represents.

Topics: Biomarkers; Cardiotonic Agents; Diuretics; Heart Failure; Hemodynamics; Humans; Hydrazones; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Pyridazines; Pyridines; Risk Assessment; Simendan; Tetrazoles; Therapeutics; Troponin; Vasodilator Agents; Ventricular Function, Left; Ventricular Pressure

Traditional medical treatment of acute heart failure has remained unchanged for many years. It has been based on oxygen supplementation and mechanical ventilatory support as well as the administration of morphine, diuretics, nitrates and inotropic agents. In 2005 the European Society of Cardiology published new guidelines on diagnosis and treatment. Also, new therapies have been introduced recently, giving rise to changes in therapeutic concepts.. The article is based on these new guidelines and recent studies selected from the literature.. Mechanical ventilatory support reduces the number of patients who require endotracheal intubation. Nitrates in higher dosages than employed today appear to be beneficial to patients with pulmonary congestion, probably because of the pronounced afterload reducing effect. Nesiritide has shown better haemodynamic effects than common nitrate dosages in patients with congestive heart failure. Tezosentan was tested in the biggest trial ever which, however, was terminated prematurely, because of futility with regard to the endpoints dyspnoea and death. Dobutamine and milrinone are associated with increased mortality in patients with pronounced chronic and acute congestive heart failure. Levosimendan has shown lower mortality compared to dobutamine in patients with acute congestive heart failure.. New concepts have finally emerged, including the application of old drugs such as nitrates in new (i.e., higher) dosages, as well as the novel compound levosimendan, and hypoperfused organs without severe hypotension. The new European Society of Cardiology classification provides a valuable and long-awaited guideline to diagnosis and treatment.

Topics: Acute Disease; Adrenergic beta-Agonists; Cardiotonic Agents; Continuous Positive Airway Pressure; Diuretics; Dobutamine; Furosemide; Heart Failure; Humans; Hydrazones; Isosorbide Dinitrate; Natriuretic Agents; Natriuretic Peptide, Brain; Nitric Oxide Donors; Oxygen Inhalation Therapy; Practice Guidelines as Topic; Pyridazines; Simendan; Vasodilator Agents

The treatment of acute heart failure is gaining importance, specifically in the perioperative setting. Increasing evidence shows that established forms of therapy using beta-adrenergic inotropic drugs have no effect on long-term survival; thus, anesthetists and intensive care specialists are focusing on new strategies. This review examines, with respect to the literature of the past year, whether these strategies will gain significance in the perioperative setting.. Owing to its unique efficacy profile, levosimendan, a calcium sensitizer, improves long-term survival in patients with acute heart failure and has been incorporated into the European Society of Cardiology guidelines. Improved heart function without increased oxygen consumption, anti-ischemic effects, no arrhythmogenic effect and positive effects on intestinal perfusion have been described. Despite the positive effects on hemodynamics and symptoms, tezosentan, an endothelin antagonist, did not improve outcome, perhaps due to too high dosages of the drug. Nesiritide, a recombinant brain natriuretic peptide, may represent an alternative to nitroglycerin and dobutamine and possibly have a benefit for survival. No final conclusions can yet be drawn, however. L-NAME, a nitric oxide synthase antagonist, represents a promising new approach for the treatment of cardiogenic shock. The results must be confirmed in large, randomized studies.. For perioperative treatment of acute heart failure, levosimendan, nesiritide and L-NAME constitute promising alternatives to conventional inotropic and vasodilatory drugs. The strongest evidence for improving outcome is given for levosimendan. According to the present literature, tezosentan does not currently have any significance for treatment of perioperative heart failure.

Topics: Calcium Signaling; Cardiotonic Agents; Cardiovascular Agents; Endothelins; Enzyme Inhibitors; Heart Failure; Humans; Hydrazones; Natriuretic Peptide, Brain; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pyridazines; Pyridines; Simendan; Tetrazoles

Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity.

Topics: Cardiovascular Diseases; Celecoxib; Cell Proliferation; Clinical Trials as Topic; Cyclooxygenase Inhibitors; Heart Failure; Hemostasis; Humans; Hypertension; Lactones; Naproxen; Natriuretic Peptide, Brain; Peptide Fragments; Pyrazoles; Sulfonamides; Sulfones

Dyspnea is a frequent reason for emergency consultations in hospitals or community medical facilities. Besides heart failure, a wide variety of other disorders may cause this symptom. Thus, early and accurate differential diagnosis is mandatory in order to facilitate rapid institution of appropriate therapy. This CME article elaborates on the specific usefulness of traditional diagnostic tools as history, symptomatology and physical signs along with chest X-ray and ECG and the more recently introduced natriuretic peptides to discriminate heart failure from other causes of dyspnea in the emergency setting. According to a systematic search and meta-analysis of the respective literature, several features from history and physical examination as well as pulmonary congestion on chest X-ray, atrial fibrillation and a high level of confidence of the initial clinical judgment indicate a cardiac cause of dyspnea with high specificity, but less sensitivity. Thus, in patients presenting with one or several of these characteristic features, little further diagnostic yield is to be expected from natriuretic peptides. If, however, the suspicion of heart failure remains unsettled by these means, determination of biomarkers may be helpful, although it needs to be considered that moderately elevated levels have only a limited specificity in particular in elderly patients with comorbidities. As also recognized by the European Guidelines for diagnosis and treatment of chronic heart failure, a BNP level of <100 pg/ml has proven particularly useful for excluding heart failure. Thus, a directed history, symptoms, physical findings, chest-X-ray and ECG remain the diagnostic mainstay. If the diagnosis cannot be established by these traditional tools, BNP or NT-proBNP testing may be very helpful, especially for ruling out heart failure.

Topics: Diagnosis, Differential; Dyspnea; Electrocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain; Radiography, Thoracic

The clinical relevance of brain natriuretic peptide (BNP) and N-terminal (NT)-proBNP assays as a diagnostic tool and prognostic marker in patients with cardiovascular diseases has recently been confirmed. However, several studies demonstrated variation of intra-individual BNP concentrations of >30% (ranging from 30% to 50%) with reference change values at the 95% confidence interval (i.e., the estimated critical difference) ranging from 99% to 130% in healthy subjects and heart failure patients. According to this estimated confidence interval, only a great variation in plasma BNP levels should be considered significant in an individual patient (for example, a decrease of >50% or an increase of more than two-fold). Many recent clinical studies have demonstrated that BNP variations below this estimated critical difference could also have clinical relevance. Like the concentration of other neuro-hormones, levels of plasma BNP fluctuate widely and rapidly along with heart rhythm and blood pressure variations in response to physiological stimuli. However, biological variation of BNP should not be interpreted strictly as random fluctuation around a homeostatic set point, as assumed by the common model used in all studies on biological variation of BNP reported in the literature. These results cannot be directly transferred to clinical practice. While awaiting more accurate studies, we suggest that variations of plasma BNP three-fold greater than the analytical imprecision should be considered as potentially relevant from a physiological and clinical point of view.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results

This review focuses on recent literature pertaining to the role of B-type natriuretic peptide (BNP) in heart failure.. Heart failure is a common disorder that is associated with significant mortality and morbidity. The diagnosis of heart failure may at times be difficult when using conventional tools. The cardiac natriuretic peptides, particularly BNP, have evolved to be useful biomarkers in heart failure and other cardiovascular disorders. Recent studies have established a close association between plasma BNP and the amino-terminal fragment of the BNP prohormone (NT-proBNP) with the diagnosis of heart failure and independent prediction of mortality and heart failure events. Furthermore, preliminary data from randomized controlled trials suggest that knowledge of BNP and/or NT-proBNP level may optimize the management of patients with heart failure. Exogenous natriuretic peptide in the form of recombinant human BNP (nesiritide) has been shown to improve hemodynamics and dyspnea and is approved in the USA and several other countries for the management of patients with acute decompensated heart failure. The effect of nesiritide on clinical outcome, however, remains unclear.. When used in the appropriate clinical settings, BNP or NT-proBNP testing is extremely useful in establishing diagnosis and predicting prognosis in heart failure. Nesiritide holds promise in the management of patients with acute decompensated heart failure. Large-scale randomized controlled trials to evaluate BNP/NT-proBNP-guided therapy are currently in progress and studies of the impact of exogenous BNP on clinical outcomes in heart failure are likely to be forthcoming.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Randomized Controlled Trials as Topic

B-type natriuretic peptide (BNP) is increasingly being used as a diagnostic marker in the diagnosis of heart failure. Here we evaluate the evidence base for its utility in the ED. Clinical trials suggest that it is more accurate than clinical acumen especially when emergency physicians have diagnostic problems. BNP appears more accurate than any clinical findings or radiological signs. In conjunction with considered clinical judgement, knowledge of its limitations and variable cut-off points, BNP can be of considerable utility to the emergency physician.

Topics: Age Factors; Atrial Natriuretic Factor; Cost-Benefit Analysis; Decision Making; Emergency Service, Hospital; Heart Failure; Humans; Medical History Taking; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity

Topics: Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

Brain or B-type natriuretic peptide (BNP) is a potent natriuretic, diuretic and vasorelaxant peptide and inhibits sympathetic tone, the renin-angiotensin-aldosterone system, and synthesis of vasoconstrictive molecules. The major source of plasma BNP is the cardiac ventricles. Elevated plasma BNP concentrations correlate with increased left ventricular (LV) filling pressure. Therefore BNP is a useful biomarkers as a screening tool for LV dysfunction. It also is a strong diagnostic indicator for both systolic and diastolic LV dysfunction. Measurement of plasma BNP is proved to be not only an efficient but also a cost effective screening tool for identifying patients with acute dyspnea of unknown etiology.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Biomarkers; Coronary Artery Disease; Emergency Treatment; Heart Failure; Heart Valve Diseases; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Congestive heart failure (CHF) is a major public health problem. The use of B-type natriuretic peptide (BNP) tests shows promising diagnostic accuracy. Herein, we summarize the evidence on the accuracy of BNP tests in the diagnosis of CHF and compare the performance of rapid enzyme-linked immunosorbent assay (ELISA) and standard radioimmunosorbent assay (RIA) tests.. We searched electronic databases and the reference lists of included studies, and we contacted experts. Data were extracted on the study population, the type of test used, and methods. Receiver operating characteristic (ROC) plots and summary ROC curves were produced and negative likelihood ratios pooled. Random-effect meta-analysis and metaregression were used to combine data and explore sources of between-study heterogeneity.. Nineteen studies describing 22 patient populations (9 ELISA and 13 RIA) and 9093 patients were included. The diagnosis of CHF was verified by echocardiography, radionuclide scan, or echocardiography combined with clinical criteria. The pooled negative likelihood ratio overall from random-effect meta-analysis was 0.18 (95% confidence interval [CI], 0.13-0.23). It was lower for the ELISA test (0.12; 95% CI, 0.09-0.16) than for the RIA test (0.23; 95% CI, 0.16-0.32). For a pretest probability of 20%, which is typical for patients with suspected CHF in primary care, a negative result of the ELISA test would produce a posttest probability of 2.9%; a negative RIA test, a posttest probability of 5.4%.. The use of BNP tests to rule out CHF in primary care settings could reduce demand for echocardiography. The advantages of rapid ELISA tests need to be balanced against their higher cost.

Topics: Biomarkers; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Radioimmunoassay; Reproducibility of Results

To review the natriuretic hormone system and discuss its diagnostic, prognostic, and therapeutic potential in critically ill children.. A thorough literature search of MEDLINE was performed using search terms including heart defects, congenital; cardiopulmonary bypass, atrial natriuretic factor; natriuretic peptide, brain; carperitide; nesiritide. Preclinical and clinical investigations and review articles were identified that describe the current understanding of the natriuretic hormone system and its role in the regulation of vascular tone and fluid balance in healthy adults and children and in those with underlying cardiac, pulmonary, and renal disease.. A predictable activation of the natriuretic hormone system occurs in children with congenital heart disease and congestive heart failure. Further study is needed to confirm preliminary reports that measurement of natriuretic hormone levels in critically ill children provides diagnostic and prognostic information, as has been demonstrated in adult cardiac populations. Natriuretic hormone infusions provide favorable hemodynamic changes and symptomatic relief when used in adults with decompensated congestive heart failure, and uncontrolled case series suggest that similar benefits may exist in children. The biological activity of the natriuretic hormone system may be decreased following pediatric cardiopulmonary bypass, and additional studies are needed to determine whether natriuretic hormone infusions provide clinical benefit in the postoperative period. Preliminary reports suggest that natriuretic hormone infusions cause physiologic improvements in adults with acute lung injury and asthma but not in those with acute renal failure.. Although important perturbations of the natriuretic hormone system occur in critically ill infants and children, further investigation is needed before the measurement of natriuretic peptides and the use of natriuretic hormone infusions are incorporated into routine practice.

Topics: Adolescent; Atrial Natriuretic Factor; Biomarkers; Cardiopulmonary Bypass; Child; Child, Preschool; Critical Care; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn; Natriuretic Agents; Natriuretic Peptide, Brain

In the normal heart, the endocrine capacity resides in the atria. Atrial myocytes express and secrete natriuretic hormones that regulate fluid homeostasis and blood pressure. But in ventricular disease, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression is also activated in ventricular myocytes. Plasma concentrations of natriuretic peptides and their biosynthetic precursors are accordingly increased in patients with marked ventricular dysfunction. In contrast, atrial peptide secretion in ventricular disease has received less attention, and our present understanding of the endocrine atria during ventricular dysfunction is still scarce. Although ventricular disease and increased circulating concentrations are associated, it does not entail that the ventricle is the sole or even the main source in all types of heart disease. Clearly, the endocrine atria are also active in heart failure. Plasma measurement of cardiac natriuretic peptides and their molecular precursors can perhaps help us to discriminate when, where and how.

Topics: Atrial Fibrillation; Heart Atria; Heart Failure; Humans; Microscopy, Confocal; Myocytes, Cardiac; Natriuretic Peptide, Brain

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Coronary Disease; Defibrillators, Implantable; Diabetes Complications; Disease Progression; Female; Follow-Up Studies; Health Surveys; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Mass Screening; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Pacemaker, Artificial; Practice Guidelines as Topic; Prevalence; Severity of Illness Index; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

Acute dyspnea is frequent in emergency medicine. The B-type natriuretic peptide is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. Conversely, NT-proBNP has no physiological activity. BNP and NT-proBNP concentration closely correlate to various indicators of heart failure.. Numerous studies have demonstrated high usefulness of BNP and NT-proBNP to diagnose heart failure, which is the main cause of acute dyspnea in emergency medicine. The diagnostic accuracy of BNP and NT-proBNP seems similar, and is higher than that of the emergency physician. Bedside dosages are now available, with high sensibility and specificity for the diagnosis of heart failure. For BNP, threshold value is ranging from 100 to 300 pg/ml in patients aged over 65 years; for NT-proBNP the threshold value is 1000 to 2000 pg/ml in elderly patients. Briefly, heart failure is unlikely when BNP is below 100 pg/ml (NT-proBNP<500 pg/ml), and very likely when BNP is higher than 400 pg/ml (or NT-proBNP>2000 pg/ml).. Early rapid measurement of BNP could improved the evaluation and treatment of patients with acute dyspnea and reduce the total cost of treatment.

Topics: Acute Disease; Biomarkers; Dyspnea; Emergency Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Sensitivity and Specificity

Ever since the publication of the large scale clinical trials of morbid-mortality, the recommendations concerning the medical treatment of cardiac failure are clear with respect to ACE inhibitors, betablockers, angiotensin receptor antagonists and aldosrerone antagonists with established target doses. As far as the prescription of diuretics go, drugs which are effective in a condition associated with a poor quality of life, it is important to use the minimal dosage because of their deleterious stimulant effects on the rennin-angiotensin-aldosterone system and their metabolic side effects. A review of the clinical trials shows that almost all patients were prescribed diuretics; in over 80% of cases, the drugs are loop diuretics with a preference for furosemide, with increasing doses during the follow-up, infrequently associated with thiazide diuretics. In the short term, diuretics reduce the circulating volume and the BNP. In the long term, high doses are associated with a poor prognosis. The clinician then has to decide on the basis of few objective criteria, especially for the reduction of dosage, despite the introduction of the BNP whose role as an aid to prescription remains to be defined. In addition to the simple prescription of drugs, a global approach to patient management is necessary in cardiac failure; in this context, concerning salt- water equilibrium and diuretics, therapeutic education may have a solid role to play to provide an acceptable quality of life including the reduction of the number of frequent hospital admissions.

Topics: Age Factors; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain; Water-Electrolyte Imbalance

Topics: Adrenomedullin; Animals; Aspartic Acid Endopeptidases; Atrial Natriuretic Factor; Disease Models, Animal; Endothelin-Converting Enzymes; Endothelins; Heart Failure; Intracellular Signaling Peptides and Proteins; Metalloendopeptidases; Natriuretic Peptide, Brain; Nitric Oxide; Oxidative Stress; Peptides; Protein Serine-Threonine Kinases; Rats; Rats, Inbred Dahl; Renin-Angiotensin System; rho-Associated Kinases

Anemia, defined as a hemoglobin level of less than 12 g/dL, often is seen in congestive heart failure (CHF). It is associated with an increased mortality and morbidity and increased hospitalizations. Compared with nonanemic patients the presence of anemia also is associated with worse cardiac clinical status, more severe systolic and diastolic dysfunction, a higher beta natriuretic peptide level, increased extracellular and plasma volume, a more rapid deterioration of renal function, a lower quality of life, and increased medical costs. The only way to determine if anemia is merely a marker for more severe CHF or actually is contributing to the worsening of the CHF is to correct the anemia and see if this favorably influences the CHF. In several controlled and uncontrolled studies, correction of the anemia with subcutaneous erythropoietin (EPO) or darbepoetin in conjunction with oral and intravenous iron has been associated with an improvement in clinical status, number of hospitalizations, cardiac and renal function, and quality of life. However, larger, randomized, double-blind, controlled studies still are needed to verify these initial observations. The effect of EPO may be related partly to its nonhematologic functions including neovascularization; prevention of apoptosis of endothelial, myocardial, cerebral, and renal cells; increase in endothelial progenitor cells; and anti-inflammatory and antioxidant effects. Anemia also may play a role in increasing cardiovascular morbidity in chronic kidney insufficiency, diabetes, renal transplantation, asymptomatic left ventricular dysfunction, left ventricular hypertrophy, acute coronary syndromes including myocardial infarction and chronic coronary heart disease, and in cardiac surgery. Again, controlled studies of correction of anemia are needed to assess its importance in these conditions. The anemia in CHF mainly is caused by a combination of renal failure and CHF-induced increased cytokine production, and these can both lead to reduced production of EPO, resistance of the bone marrow to EPO stimulation, and to cytokine-induced iron-deficiency anemia caused by reduced intestinal absorption of iron and reduced release of iron from iron stores. The use of angiotensin-converting enzyme inhibitor and angiotensin receptor blockers also may inhibit the bone marrow response to EPO. Hemodilution caused by CHF also may cause a low hemoglobin level. Renal failure, cardiac failure, and anemia therefore all interact

Topics: Anemia; Animals; Attitude; Cardiology; Erythropoietin; Heart Diseases; Heart Failure; Hemoglobins; Humans; Internal Medicine; Iron; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Nephrology; Recombinant Proteins

Decompensation in patients with congestive heart failure remains a treatment problem. Earlier detection of decompensation may result in a lessened need for hospitalization and perhaps an interruption of the as-yet-undetermined processes during decompensation that lead to an adverse effect on the natural history of heart failure. B-type natriuretic peptide is produced by right and/or left ventricular tissue in response to an increase in ventricular wall stress and may be used as an indicator of decompensation. New directions in monitoring now include novel device-based algorithms that determine either intraventricular pressure or intrathoracic impedance. When combined with clinical assessment, weight monitoring, and symptom assessment, these newer monitoring platforms may yield improvements in the natural history of heart failure.

Topics: Biomarkers; Cardiac Catheterization; Cardiography, Impedance; Early Diagnosis; Edema; Edema, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Prognosis; Pulmonary Wedge Pressure; Ventricular Function, Left

The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular homeostasis. They have recently emerged as potentially important clinical markers in heart failure. Recent data have suggested an important role for these markers in establishing the diagnosis of heart failure in patients with unexplained dyspnea in both acute care and ambulatory settings. Other clinical uses of the natriuretic peptides, such as screening for asymptomatic ventricular dysfunction, establishing prognosis or guiding titration of drug therapy, are under investigation but have not yet sufficiently been validated for widespread clinical use.

Topics: Atrial Natriuretic Factor; Bayes Theorem; Biomarkers; Dyspnea; Heart Failure; Humans; Likelihood Functions; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reference Values; ROC Curve; Sensitivity and Specificity; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Animals; Biomarkers; Heart Failure; Humans; Hypertension; Immunoenzyme Techniques; Natriuretic Peptide, Brain; Peptide Fragments

Nesiritide is the recombinant form of human B-type (brain) natriuretic peptide (BNP), and its amino acid sequence is identical to that of endogenous human BNP. Administration of nesiritide results in venous and arterial vasodilation, as well as enhanced diuresis. Given the many limitations of therapies previously available for the treatment of acute decompensated heart failure, the anticipation was that nesiritide would offer a safer and more effective therapeutic option. Recently, two meta-analyses raised the question of safety with nesiritide therapy, specifically an increased risk of renal dysfunction and mortality. Although several studies generated information regarding the potential role of nesiritide in various settings, the questions raised by the meta-analyses are concerning. Our hope is that future clinical trials will address the concerns raised and provide a better understanding of the role of nesiritide in the management of acute decompensated heart failure. Until these data are available, nesiritide use should be limited.

Topics: Acute Disease; Heart Failure; Humans; Kidney; Length of Stay; Natriuretic Agents; Natriuretic Peptide, Brain

Hospital admissions with heart failure (HF) are increasing worldwide. It is the main reason for hospitalization of elderly patients. Heart failure affects nearly 15% of patients aged >75 years. Prognosis after diagnosis of HF is comparable to that of cancers with 50% survival after 4 years of mild HF and 50% after one year in more severe cases. Current data increasingly suggest that measurement of brain natriuretic peptide (BNP) is very useful in diagnosis, treatment, prognosis and risk stratification of patients with HF and beyond. This paper reviews the available literature concerning the BNP and N-terminal pro brain-type natriuretic peptide to assess their role in current medical practice.

Topics: Heart Diseases; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Randomized Controlled Trials as Topic

COPD affects up to one third of patients with chronic heart failure. The coexistence of COPD and chronic heart failure presents clinicians with diagnostic and therapeutic challenges. Measurement of B-type natriuretic peptide plasma levels facilitates the diagnosis of acute dyspnea in patients known to have both COPD and chronic heart failure. Patients with COPD or chronic heart failure have skeletal muscle abnormalities that limit functional capacity independently from primary organ failure. Exercise training reverses skeletal muscle abnormalities in patients with COPD or chronic heart failure and may be particularly indicated in patients with coexistent COPD and chronic heart failure.

Topics: Biomarkers; Exercise; Heart Failure; Humans; Muscle Weakness; Muscular Atrophy; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

In the past decade a large amount of attention has been focused on brain natriuretic peptide (BNP) testing in the evaluation of patients with acute dyspnea as well as the screening of patients for congestive heart failure (CHF). Because BNP is secreted by myocytes in response to ventricular stretch, it has long been thought that BNP could become a biochemical marker for CHF. Rapid assays have been developed and BNP testing has been studied in detection of CHF and predictive outcomes in a large variety of settings. We review the clinical evidence associated with the use of BNP testing in the acute care setting. We conclude with a discussion of clinical utility in the emergency department for the evaluation of patients presenting with acute dyspnea.

Topics: Acute Kidney Injury; Biomarkers; Dyspnea; Emergencies; Heart Failure; Humans; Natriuretic Peptide, Brain; Point-of-Care Systems; Sensitivity and Specificity; Ventricular Dysfunction, Left

Standard therapy for acute decompensated heart failure, a major health problem, consists of intravenous diuretics, vasodilators, and positive inotropic agents. Nesiritide, a recombinant form of human B-type natriuretic peptide, is the only drug specifically approved for this indication. Recent meta-analyses have reported an increased risk of worsening renal function and 30-day mortality with nesiritide administration. These data understandably require physicians to carefully reevaluate their current use of nesiritide in patients with acute decompensated heart failure. In performing this reevaluation, it is important to consider our understanding of the underlying disease state, the limitations and results of these meta-analyses, and new data that provide additional insight into the possible risks and benefits associated with nesiritide therapy. Until additional therapeutic trials are conducted, therapeutic choices must be based on symptomatic and hemodynamic improvement and limited, imperfect available data, which may continue to support the use of nesiritide for its established indication.

Topics: Acute Disease; Creatinine; Decision Making; Heart Failure; Humans; Meta-Analysis as Topic; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Research Design; Risk Assessment; Risk Factors

B-Type natriuretic peptide (BNP) and NTpro-BNP are widely used for diagnosis and risk stratification of patients with heart failure (HF). Although not currently cleared by the Food and Drug Administration as a test indication, there is interest in using these biomarkers for monitoring the success of HF medications. An assessment of the analytical and biologic variations is necessary to interpret the results of serial testing.. The intra-individual biologic variances and analytical assay variances of BNP and NT-proBNP from healthy subjects and those with stable HF were reviewed. The analytical variability of BNP and NT-proBNP assays was reported, as some have suggested that only the analytical variance is important in interpreting the results of tightly regulated hormones. The reference change values (RCV) for serial measurements were derived and used to interpret results of therapeutic studies whereby serial changes in BNP and NT-proBNP concentrations were obtained to evaluate the therapeutic success of short-term (inpatient) and long-term (outpatient) management. The use of RCV may also be important in studies comparing BNP-guided versus physician-guided HF drug therapy.. Relative to the RCV, short-term therapeutic studies of inpatients have largely resulted in a statistically significant decline in BNP and NT-proBNP with clinical evidence of patient improvements. In contrast, many therapeutic studies involving long-term outpatient monitoring have produced changes in BNP/NT-proBNP that do not exceed the biologic variances. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values

Chronic heart failure (CHF) is a major cause of morbidity and mortality in industrialized countries. As societies are aging, efforts are directed toward early interventions to preserve quality of life as well as lower mortality. However, because of the paucity of specific symptoms, an early diagnosis and management of CHF might be challenging. In contrast, biochemical markers, which can be measured easily and without inter-observer variability, are now being carefully examined. Since CHF is a complex syndrome, a single biochemical marker cannot reflect its multiple manifestations. An ideal biochemical marker should 1) be a prognostic indicator, 2) reflect the therapeutic response, 3) be heart specific 4) be independent from other markers 5) reflect the pathophysiology of CHF, 6) assist in the early diagnosis of CHF, and 7) be reliable throughout the various phases of the syndrome, from before the onset of its clinical manifestations through its end-stage. This review summarizes our current understanding of biochemical markers of CHF based on its pathophysiology.

Topics: Biomarkers; Collagen; Heart Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Observer Variation; Prognosis; Reproducibility of Results; Risk; Treatment Outcome; Troponin

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cost of Illness; Disease Progression; Diuretics; Drug Monitoring; Drug Therapy, Combination; Female; Fluorescence Polarization Immunoassay; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Nurse's Role; Point-of-Care Systems; Predictive Value of Tests; Primary Health Care; Prognosis; Reference Values; Treatment Outcome; United States

Nesiritide (recombinant human B-type natriuretic peptide) has been shown to provide symptomatic and hemodynamic improvement in acute decompensated heart failure. A previous meta-analysis of 3 randomized controlled trials has suggested an increased short-term risk of death with nesiritide use. We performed a meta-analysis of 7 available randomized controlled trials to evaluate the short- and long-term risk of death with nesiritide use for acute decompensated heart failure.. Seven large randomized controlled nonmortality trials on nesiritide with available data on 30-day mortality were included. Data on 180-day mortality were available only in 4 trials. Mortality data in nesiritide and control arms were extracted from the selected trials and the nesiritide database (Scios Inc, Fremont, CA).. The pooled estimate of the relative risks (RRs) for unadjusted 30- and 180-day mortality revealed no significant differences between the nesiritide arm (RR 1.243, 95% CI 0.798-1.935) and control arm (RR, 0.002, 95% CI 0.798-1.259), respectively).. Unlike a previous analysis, our meta-analysis indicates that nesiritide is not associated with a higher 30- or 180-day mortality. Further analysis of mortality adjusted for confounding variables such as nesiritide dose, duration of infusion, concurrent use of inotropes, heart failure stage, and arrhythmias may reveal subgroups in jeopardy. Large-scale randomized controlled trials powered to evaluate mortality are required to conclusively address these findings.

Topics: Acute Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Risk; Time Factors

Renal insufficiency is becoming an increasingly common and devastating comorbidity in both acute and chronic heart failure settings. Part of the problem is due to the lack of insight into the underlying pathophysiology of salt and water balance leading to the congestive states. This review summarizes our current understanding regarding the cause and consequences of renal insufficiency in patients with heart failure, and addresses some of the limitations of current therapeutic strategies. Based on these limitations, this paper will explore the ongoing efforts to develop novel drug therapeutics to prevent or ameliorate renal impairment in patients with heart failure. These include natriuretic peptides and other vasodilators, adenosine receptor antagonists, and vasopressin receptor antagonists all currently undergoing late-stage clinical trials.

Topics: Adenosine; Angiotensin-Converting Enzyme Inhibitors; Antidiuretic Agents; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Neurotransmitter Agents; Prognosis; Renal Insufficiency; Treatment Outcome; Vasodilator Agents; Vasopressins

Brain natriuretic peptide (BNP) levels are simple and objective measures of cardiac function. These measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money in the emergency department setting. The high negative predictive value of BNP tests is particularly helpful for ruling out heart failure. Treatment with angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, spironolactone, and diuretics reduces BNP levels, suggesting that BNP testing may have a role in monitoring patients with heart failure. However, patients with treated chronic stable heart failure may have levels in the normal range (i.e., BNP less than 100 pg per mL and N-terminal proBNP less than 125 pg per mL in patients younger than 75 years). Increases in BNP levels may be caused by intrinsic cardiac dysfunction or may be secondary to other causes such as pulmonary or renal diseases (e.g., chronic hypoxia). BNP tests are correlated with other measures of cardiac status such as New York Heart Association classification. BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Biomarkers; C-Reactive Protein; Cytokines; Fatty Acid-Binding Proteins; Heart Failure; Humans; Inflammation; Myosin Light Chains; Natriuretic Peptide, Brain; Norepinephrine; Nurse's Role; Nursing Assessment; Peroxidase; Prognosis; Risk Assessment; Sensitivity and Specificity; Troponin

This paper explains the background and current use of B-type natriuretic peptide (BNP) assays to differentiate congestive heart failure (CHF) from other causes of dyspnea. With a large and growing elderly population, CHF is being diagnosed much more often in emergency rooms in the United States. Doctors need a way to quickly distinguish whether a patient with respiratory distress is suffering from cardiac insufficiency or another etiology. BNP is released from the ventricles in response cardiac overload from CHF or some other form of left ventricular systolic dysfunction. Therefore, the detection and measurement of BNP is a fast and accurate method of determining if CHF is the cause of a patient's breathing difficulties.

Topics: Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests

Heart failure (HF) is a prevalent and morbid chronic disease that patients experience in stages. Progression through the stages of HF can be slowed with optimal medical therapy. Although HF remains a clinical diagnosis made at the bedside, measurement of serum brain natriuretic peptide (BNP) can help in the diagnosis when there is uncertainty. The initial workup for patients with newly diagnosed HF is directed at identifying the underlying cause of left ventricular dysfunction. An assessment of hemodynamic status, determined by a careful physical examination, can be used to direct therapy. Angiotensin-converting enzyme inhibitors (ACEIs) and beta blockers remain the two most important therapies for patients with chronic HF. Aldosterone antagonists improve mortality but require close monitoring for severe hyperkalemia. Angiotensin-receptor blockers (ARBs) are excellent alternatives to ACEIs for ACEI-intolerant patients. Digoxin, a second line agent in HF, improves symptoms without mortality benefit. Successful management of HF requires aggressive management of comorbid conditions and careful follow up to slow disease progression, optimize functional status, and improve longevity.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Predictive Value of Tests

Topics: Acute Disease; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Heart failure (HF) has a high incidence, near 2% of the population suffered this process, that increases with the age, affecting between 15-20 % of the population elder than 70 years. In the last 20 years the knowledge in pathophysiological mechanisms has improved, mainly, the role of neurohormonal response in the development and worsening of HF. In the last 15 years the efficient blockade of these mechanisms have improved the follow-up of these patients. The use of Angiotensin Converting Enzyme inhibitors, angiotensin II receptor blockers, Beta-blockers and antialdosteronic drugs have significantly decreased cardiovascular morbidity and mortality of these patients. Nevertheless 50% of patients with HF dies for electrical disturbance of the ventricular rithm, tachycardia and ventricular fibrillation. Also, disorders of intraventricular conduction worsen the functional degree. The implantable cardioverter defibrillator reduce mortality in patients at higher risk for mortality due to HF and Cardiac Resynchronization Therapy may lead to remarkable improvement in clinical status in selected patients with HF. Other measures, as cardiac transplantsand implantable left ventricular assist devices are becaming more exceptional in all occidental countries. Cell transplantation is an innovative technology and has the potential to revolutionize alternative therapeutic approaches to management of heart failure, but still a numkber of problems persist before the extending use of these techniques.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiotonic Agents; Clinical Trials as Topic; Defibrillators, Implantable; Diuretics; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Nitroglycerin; Patient Selection; Prognosis; Vasodilator Agents

The purpose of this systematic review was to evaluate BNP and NT-proBNP to: (a) identify determinants, (b) establish their diagnostic performance in heart failure (HF) patients, (c) determine their predictive ability with respect to mortality and other cardiac endpoints, and (d) determine their value in monitoring HF treatment.. MEDLINE, EMBASE, CINAHL, Cochrane Central, and AMED from 1989 to February 2005 were searched for primary studies.. Standard systematic review methodology, including meta-analysis, was employed. All study designs were included. Eligibility criteria included English-only studies and restricted the number of test methods to maximize generalizability. Outcomes for prognosis were limited to mortality and specific cardiac events. Further specific criteria were developed for each research question.. Determinants: There were 103 determinants identified including age, gender, disease, treatment, as well as biochemical and physiological measures. Few studies reported independent associations and of those that did age, female gender and creatinine levels were positively associated with BNP and NT-proBNP.. Pooled sensitivity and specificity values were 94 and 66 percent for BNP and 92 and 65 percent for NT-proBNP; there was minimal difference among settings (emergency, specialized clinics, and primary care). B-type natriuretic peptides also added independent diagnostic information above traditional measures for HF.. Both BNP and NT-proBNP were found to be independent predictors of mortality and other cardiac composite endpoints in patients with risk of coronary artery disease (CAD) (risk estimate range = 1.10 to 5.40), diagnosed CAD (risk estimate range = 1.50 to 3.00), and diagnosed HF patients (risk estimate range = 2.11 to 9.35). With respect to screening, the AUC values (range = 0.57 to 0.88) suggested poor performance. Monitoring Treatment: Studies showed therapy reduced BNP and NT-proBNP, however, relationship to outcome was limited and not consistent.. Determinants: The importance of the identified determinants for clinical use is not clear.. In all settings both BNP and NT-proBNP show good diagnostic properties as a rule out test for HF.. BNP and NT-proBNP are consistent independent predictors of mortality and other cardiac composite endpoints for populations with risk of CAD, diagnosed CAD, and diagnosed HF. There is insufficient evidence to determine the value of B-type natriuretic peptides for screening of HF. Monitoring Treatment: There is insufficient evidence to demonstrate that BNP and NT-proBNP levels show change in response to therapies to manage stable chronic HF patients.

Topics: Age Factors; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Sex Factors

Topics: Acute Disease; Biomarkers; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive

Regarding cardiac failure, the year 2004 was notable for the dissemination of indications for the use of medical devices in heart failure: indications for cardioversion with the long awaited publication of the COMPANION study, advancement of the concept of intra-ventricular asynchronism, and studies of defibrillators in non-ischaemic cardiac failure (COMPANION, DEFINITE, SCD-HeFT, TOVA). Furthermore, pragmatic clinical studies allowed refinement of the uses of BNP (diagnostic and prognostic), underlining the importance of renal function and its progression during hospitalisation, and the risks of using strong, modern therapy in populations without "ad hoc" surveillance which do not correspond with study populations (aldactone in Canada). Just as in coronary patients, it appears to be important to commence full medical treatment prior to hospital discharge, because treatment is rarely changed thereafter. The management of seriously ill patients is evolving with several therapeutic advances: the methods of selecting patients for heart transplants have changed, with the advancement of opportunities for circulatory assistance. Attention has also been turned to the significant group, still poorly understood, of patients with diastolic heart failure, for whom diagnostic methods have been defined, as well as their clinical characteristics. Lastly the medication studies: new drugs in acute cardiac failure (preliminary results for vasopressin antagonists), wider indications for betablockers in elderly subjects (SENIORS), and advances in cellular cardiomyoplasty (using haemopoietic stem cells especially this year). It has been a fruitful year, difficult to summarise in a few lines, or even several pages....

Topics: Cardiac Pacing, Artificial; Defibrillators; Heart Failure; Heart Transplantation; Humans; Kidney Function Tests; Natriuretic Peptide, Brain; Prognosis

Heart Failure is a syndrome describing a pathophysiological state with diverse etiologies. Providing an adequate mechanistic definition is difficult. The current guidelines from the European Society of Cardiology define the diagnosis of heart failure based on three criteria. Patients should have symptoms compatible with heart failure at rest or on exercise. There should be objective evidence of cardiac dysfunction at rest. In doubtful cases, there should be a favourable response following therapy for heart failure. The term diagnosis derives from the Greek words "dia" and "nosi" meaning "through knowledge". It implies that a conclusion is drawn describing the patient's current status based on the available information. This information is commonly based on the symptoms, history, findings at physical examination, results from laboratory tests, and the results from various non-invasive and invasive special examinations. Diagnostic precision is crucial in deciding treatment strategy and this task presents a continuous academic and clinical challenge. Ultimately, the clinical diagnosis of heart failure is based on all the information available to the physicians. No single investigation is specific for this clinical syndrome and management strategies attempt to modify the underlying mechanisms in order to alleviate symptoms and improve survival.

Topics: Clinical Laboratory Techniques; Coronary Angiography; Echocardiography; Exercise Test; Heart Failure; Heart Function Tests; Humans; Natriuretic Peptide, Brain; Physical Examination

B-type natriuretic peptide (BNP) and NT-proBNP are currently the most prominent members of the natriuretic peptide family. These markers are secreted from both the left and the right cardiac ventricle in response to ventricular volume expansion and pressure overload. Recent studies have suggested that these neurohormones are reliably elevated in the setting of congestive heart failure and may be very helpful in its diagnosis. The use of rapid BNP testing in addition to clinical judgement increased the accuracy of the clinical evaluation. The B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study showed that the increase in accuracy offered by rapid BNP testing resulted in a significant reduction of hospitalisations, use of intensive care, time to discharge and initial treatment cost.

Topics: Acute Disease; Biomarkers; Clinical Medicine; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Reference Values

Brain natriuretic peptide is a cardiac neurohormone that is secreted by the left ventricle in response to an increase in wall stress. Brain natriuretic peptide has emerged as a neurohormone with multiple roles in heart failure management. This review will discuss the role of brain natriuretic peptide in heart failure diagnosis, prognostic assessment, screening for asymptomatic left-ventricular dysfunction, and in the treatment of heart failure.

Topics: Biomarkers; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Recombinant Proteins

The discovery of B-type natriuretic peptide (BNP) and n-terminal pro BNP (nt-proBNP) as markers for the diagnosis, severity and prognosis of patients with congestive heart failure has been called a true breakthrough for patients and physicians faced with this disorder. Moreover, the literature on their prognostic value in other clinical conditions like acute coronary syndromes, right-sided heart failure and even in the general population is rapidly growing. This review aims to sort out the current evidence on the clinical utility of the natriuretic peptides with a focus on their diagnostic and prognostic values. With respect to their diagnostic properties, the test is best used to rule out heart failure in patients with acute dyspnoe, because low levels of these neurohormones in this clinical context make the presence of heart failure very unlikely. In patients with elevated values of BNP or nt-proBNP, further cardiological assessment is necessary, as their plasma levels are affected not only by left ventricular function.

Topics: Biomarkers; Clinical Trials as Topic; Coronary Disease; Heart Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Ventricular Dysfunction, Left

We report the case of a female patient emergently transferred to our institution with the presumptive diagnosis of myocardial infarction in heart failure given the constellation of symptoms and abnormal laboratory cardiac markers on presentation. However, on closer examination, prior to instituting an invasive cardiac work-up, pulmonary embolism was instead strongly considered to explain a common etiology. Therefore, an echocardiogram was promptly obtained, which revealed the presence of McConnell's sign. This noninvasive imaging modality proved to be critical in the prompt recognition and management of this patient. We reviewed the literature regarding the use of echocardiography and the clinical significance of abnormal cardiac markers in patients presenting pulmonary embolism.

Topics: Aged; Diagnosis, Differential; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Myocardial Infarction; Natriuretic Agents; Natriuretic Peptide, Brain; Pulmonary Embolism; Tibia; Troponin I; Venous Thrombosis

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

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Severity of Illness Index

To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure.. Systematic review of studies assessing BNP for prognosis in patients with heart failure or asymptomatic patients.. Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies.. We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data.. 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance-that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk.. Although systematic reviews of prognostic studies have inherent difficulties, including the possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients and for patients with heart failure at all stages of disease.

Topics: Biomarkers; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; Survival Analysis

Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF.. Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine >0.5 mg/dL. Relative risk across all studies was determined by meta-analysis with Mantel-Haenszel fixed-effects models (RR(MH)). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration-approved doses of nesiritide (< or =0.03 microg x kg(-1) x min(-1)) significantly increased the risk of worsening renal function compared with non-inotrope-based control (RR(MH), 1.52; 95% CI, 1.16 to 2.00; P=0.003) or any control therapy, including non-inotrope- and inotrope-based therapies (RR(MH), 1.54; 95% CI, 1.19 to 1.98; P=0.001). Even low-dose nesiritide (< or =0.015 microg x kg(-1) x min(-1)) significantly increased risk (P=0.012 and P=0.006 compared with non-inotrope- and inotrope-based controls, respectively), as did nesiritide administered at any dose up to 0.06 microg x kg(-1) x min(-1) (P=0.002 and P=0.001, respectively). There was no difference in the need for dialysis between therapies.. Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.

Topics: Creatine; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Risk

Topics: Cardiotonic Agents; Electrocardiography; Heart Failure; Humans; Life Style; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Referral and Consultation; Terminal Care; Weight Loss

Nesiritide improves symptoms in patients with acutely decompensated heart failure compared with placebo and appears to be safer than dobutamine. Its short-term safety relative to standard diuretic and vasodilator therapies is less clear.. To investigate the safety of nesiritide relative to noninotrope-based control therapies, primarily consisting of diuretics or vasodilators.. Primary reports of completed clinical trials as of December 2004 were obtained from the US Food and Drug Administration (FDA), the study sponsor (Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations.. Of 12 randomized controlled trials evaluating nesiritide, 3 met all inclusion criteria: randomized double-blind study of patients with acutely decompensated heart failure, therapy administered as single infusion (> or =6 hours), inotrope not mandated as control, and reported 30-day mortality.. Data were extracted from FDA and sponsor documents and corroborated with published articles when available. Thirty-day survival was assessed by meta-analysis using a fixed-effects model and time-dependent risk by Kaplan-Meier analysis with Cox proportional hazards regression modeling. Where deaths were described within a range of days after treatment, an extreme assumption was made favoring nesiritide over control therapy, an approach relevant to the time-dependent analyses.. In the 3 trials, 485 patients were randomized to nesiritide and 377 to control therapy. Death within 30 days tended to occur more often among patients randomized to nesiritide therapy (35 [7.2%] of 485 vs 15 [4.0%] of 377 patients; risk ratio from meta-analysis, 1.74; 95% confidence interval [CI], 0.97-3.12; P = .059; and hazard ratio after adjusting for study, 1.80; 95% CI, 0.98-3.31; P = .057).. Compared with noninotrope-based control therapy, nesiritide may be associated with an increased risk of death after treatment for acutely decompensated heart failure. The possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of nesiritide for acutely decompensated heart failure.

Topics: Diuretics; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Vasodilator Agents

This paper reviews recent advances in heart failure biomarkers for identification of disease precursors, subclinical disease, and onset or progression of overt disease.. Heart failure biomarkers can be categorized empirically as neurohormonal mediators, markers of myocyte injury and remodeling, and indicators of systemic inflammation. Brain natriuretic peptide is the most widely studied, with a potentially important but evolving role for determining prognosis and as a surrogate endpoint in clinical trials. Strong evidence exists for use of brain natriuretic peptide in the diagnosis of acute heart failure and for improved clinical outcomes with a brain natriuretic peptide-guided approach to heart failure care. The use of brain natriuretic peptide as a screening tool for asymptomatic left ventricular systolic dysfunction, or to distinguish systolic from diastolic heart failure, is not supported by current data. Markers of myocyte injury, including troponins, heart-type fatty acid binding protein, and myosin light chain-1, may further improve heart failure prognostication in conjunction with plasma brain natriuretic peptide. Biomarkers of matrix remodeling and inflammation have emerged as potential preclinical indicators to identify individuals at risk of developing clinical heart failure. A role for cellular adhesion molecules may also emerge in identifying those at risk for cardiovascular thrombotic complications, such as stroke.. The spectrum of heart failure biomarkers and their potential clinical applications continues to grow. Ongoing research on multimarker strategies will likely identify biomarker combinations that are optimal at various stages during the evolution of heart failure, ranging from their use for screening, diagnosis, determining prognosis, and guiding management.

Topics: Biomarkers; Carrier Proteins; Fatty Acid-Binding Proteins; Heart Failure; Humans; Myocardium; Myosin Light Chains; Natriuretic Peptide, Brain; Prognosis; Severity of Illness Index; Troponin

Topics: Aged; Biomarkers; Cardiac Catheterization; Coronary Disease; Diabetes Complications; Echocardiography; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain

Congestive heart failure is a leading cause of morbidity and mortality throughout the world and is now the leading cause of hospitalizations in adults over 65 years of age with an estimated annual expenditure in excess of USD 20 billion. In addition, it is the only cardiovascular disorder that continues to increase in both incidence and prevalence, and as the population continues to age, it is expected that the prevalence of this disease will continue to rise. Ironically, the armamentarium of medications that decrease mortality due to congestive heart failure also continues to grow; however, the relative number of eligible patients with congestive heart failure (or at risk for congestive heart failure) that receive these important therapies remains low. Thus, better tools to aid the early diagnosis and management of this disease are needed. Testing for natriuretic peptide markers, such as B-type natriuretic peptide or its amino-terminal fragment, has emerged as an important tool to assist in the optimal diagnosis and risk stratification of patients with congestive heart failure and may also play a valuable role in guiding therapy.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment

Congestive heart failure (CHF) is a complex clinical syndrome characterized by dysfunction of the left, right, or both ventricles, which results in the impairment of the heart's ability to circulate blood at a rate sufficient to maintain the metabolic needs of peripheral tissues and various organs. Owing to the drastic increase in cardiovascular risk factors such as obesity, diabetes, and improved survival rate after acute myocardial infarction and subsequent development of CHF in the last quarter of a century, CHF has become a major and increasing cause of death and disability in the United States. Unfortunately, the signs and symptoms are nonspecific for CHF Also, routine laboratory values, electrocardiograms, and X-rays are not always accurate enough to make the appropriate diagnosis. Recently, the US Food and Drug Administration approved a new biomarker, B-type natriuretic peptide (BNP), for the purpose of diagnosing and assessing severity of CHE BNP is synthesized, stored, and released primarily by the ventricular myocardium in response to volume expansion and pressure overload. The use of SNP, along with other diagnostic tools, can enable care providers to facilitate and optimize care of heart failure patients in a variety of clinical settings. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Topics: Acute Disease; Biomarkers; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Syndrome; Ventricular Dysfunction, Left

Although there has been substantial progress in the treatment of congestive heart failure over the last several decades, it is clear that heart failure continues to burden our aging population. As the epidemic of heart failure grows, there remains an unmistakable need for novel diagnostic and therapeutic options in its management. In this article, we review recent innovations in the management of congestive heart failure, highlighting several recent clinical trials.

Topics: Age Factors; Biomarkers; C-Reactive Protein; Cardiovascular Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Neurotransmitter Agents; Pyridines; Thiazepines

Brain natriuretic peptide (BNP) release is a marker of increased myocardial wall tension, which is elevated in patients with disturbed left ventricular function. As it is increasingly being used as a reliable marker for diagnosis, optimization of pharmacological treatment, and risk stratification, BNP measurement might be also relevant for patients undergoing cardiac surgery. Measured BNP levels can be used to predict postoperative complications and the risk of further cardiac events. Preoperative BNP levels support the decision for the timing of aortic valve replacement in asymptomatic severe aortic stenosis. An increase in BNP levels early predicts allograft rejection after cardiac transplantation or ineffective cardiac resynchronization therapy. Moreover, BNP levels can be used to differentiate between cardiac and non-cardiac reasons for acute dyspnea in the management of surgical patients. Finally, the application of recombinant human BNP seems to improve recovery after cardiac surgical procedures. Thus, BNP can be a helpful tool for monitoring and treating patients before, during, and after cardiac surgery to predict and improve the effectiveness of therapy and reduce hospitalization and costs.

Topics: Cardiac Surgical Procedures; Coronary Artery Bypass; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Ventricular Dysfunction, Left

Natriuretic peptides are secreted by the myocardium in response to mechanical stretch and have been proposed as a possible test for assisting the diagnosis of heart failure. This article reviews the rationale for measuring N terminal probrain natriuretic peptide in pleural fluid to identify heart failure as the cause of a pleural effusion.. Rapid and accurate testing of natriuretic peptides as biomarkers for heart failure is now a clinical reality. In patients presenting with dyspnea, heart failure is usually absent at blood brain natriuretic peptide levels less than 100 pg/mL, possible from 100 to 500 pg/mL, and probable at levels greater than 500 pg/mL. In evaluating natriuretic peptide assays, one needs to consider carefully laboratory and biologic variation, including gender, sex, obesity, renal function, and the assay used. Potential future applications of natriuretic peptide testing include the differential diagnosis of pleural effusion. A recent study has shown good diagnostic characteristics in cardiac pleural effusions, with likelihood ratios of 13 and a diagnostic accuracy of more than 90% for pleural fluid N terminal probrain natriuretic peptide levels > or =1500 pg/mL. Specifically, N terminal probrain natriuretic peptide pleural levels correctly categorized most cardiac effusions misclassified as exudates by standard criteria, and discriminated between cardiac and hepatic transudates.. Pleural fluid N terminal probrain natriuretic peptide may help accurately differentiate cardiac from noncardiac conditions in patients presenting with pleural effusion.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Effusion

Topics: Acute Disease; Atrial Natriuretic Factor; Disease Progression; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Receptors, Atrial Natriuretic Factor

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Diagnosis, Differential; Electrocardiography; Female; Heart Failure; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Syndrome; Ventricular Dysfunction, Left

Since 1988 with the discovery of B-type natriuretic peptide (BNP), many reports have confirmed the elevation of plasma BNP in symptomatic heart failure and confirmed that plasma levels are an independent predictor of death and cardiovascular events in both acute and chronic heart failure.. A more slender evidence base attests that knowledge of plasma BNP levels can be used to produce clinical benefit. One randomized controlled trial demonstrated that measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used to improve diagnostic accuracy in patients with heart failure in the community. A second study demonstrated that the provision of plasma BNP data improves the speed of diagnosis and reduces the rates of hospital admission and length of hospital stay (while reducing the costs of care) in patients with heart failure who are seen the emergency department with acute dyspnea. Finally, a randomized controlled pilot study demonstrated that serial measurements of NT-proBNP can be used to more effectively optimize heart failure pharmacotherapy with a concomitant improvement in outcome.. The large body of observational data, coupled with this small but promising evidence base from controlled trials (which attests to beneficial effects on clinical outcomes) encourages an optimistic outlook for the further implementation of plasma BNP and/or NT-proBNP in the diagnosis and treatment of acute and chronic heart failure.

Topics: Cardiovascular Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Ventricular Dysfunction, Left

Although less common than in adults, heart disease is a significant cause for morbidity and death in infants and children. Congenital structural cardiac anomalies and acquired heart diseases may result in heart failure.. Available data suggest that the natriuretic peptide system has a similar role in health and disease in the pediatric age group as in adults. In healthy infants and children, levels of B-type natriuretic peptide (BNP) and the N-terminal segment of its pro-hormone (NT-proBNP) are elevated in the first few days after birth. Thereafter, their levels decrease and remain relatively constant throughout childhood. Infants and children with heart disease that causes significant pressure or volume overload of the right or the left ventricle have elevated BNP and NT-proBNP levels. In children with congestive heart failure, BNP and NT-proBNP levels correlate with functional capacity. Both peptides can differentiate cardiac from pulmonary causes in infants with respiratory distress. Limited data suggest that these peptides may also serve as markers in cyanotic, obstructive, and inflammatory heart diseases.. The present data suggest that both NT-proBNP and BNP are markers for heart disease in infants and children. Their use may improve clinical practice in pediatric cardiology.

Topics: Adolescent; Adult; Biomarkers; Cardiology; Child; Child, Preschool; Female; Heart Diseases; Heart Failure; Humans; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Pediatrics; Peptide Fragments; Predictive Value of Tests

B-type natriuretic peptide (BNP; 77-108 amino acids) and its N-terminal (1-76 amino acids) counterpart, NT-proBNP, are cardiac biomarkers that have been established for the assessment of left ventricular dysfunction and congestive heart failure and provide prognostic and risk stratification information for patients with acute coronary syndrome. Various automated immunoassays currently are available for the measurement of these natriuretic peptides, but there are significant analytical differences, especially between BNP and NT-proBNP.. Recently published methods and results were reviewed.. Although there are significant pre-analytical and analytical differences between the Triage BNP and Elecsys NT-proBNP and other BNP methods, they do not translate to clinically significant differences in their diagnostic and prognostic application in the assessment of systolic heart failure and risk stratification of patients with acute coronary syndrome. However, there appears to be some evidence that suggests that NT-proBNP may have an advantage in the detection of patients with mild or asymptomatic heart disease.

Topics: Biomarkers; Exercise; Heart Failure; Humans; Immunoassay; Ischemia; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Dysfunction, Left

Congestive heart failure (CHF) is a life-threatening cardiovascular disease that is increasing in prevalence. It is a common cause of death and is accompanied by high direct and indirect costs for treatment. The current situation faced by patients and the medical community with regard to this ailment is one of high mortality, repeated hospitalizations, and combination therapies. The various classes of pharmacological agents that are currently used for patients suffering from CHF include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), aldosterone antagonists, beta-blockers, calcium channel blockers (CCBs), digitalis drugs, diuretics, inotropic agents, nitrates, and vasodilators. While these agents are all important therapeutic tools in the treatment of CHF, the prognosis for patients with CHF remains poor. Thus improvement of the current pharmacological armamentarium is greatly needed. An endogenous peptide, B-type natriuretic peptide (BNP), has been increasingly utilized in the setting of acute CHF since its approval in 2001. This peptide, or a derivative thereof, has great potential for the treatment of patients at various stages in the progression of heart failure. This review provides an overview of current pharmacological strategies in CHF and addresses potential future developments in the use of BNP for the treatment of CHF.

Topics: Cardiotonic Agents; Disease Progression; Heart Failure; Humans; Natriuretic Peptide, Brain

Natriuretic peptides are involved in the regulation of volume homeostasis. Their levels generally are increased in the setting of volume expansion and act on multiple effector systems to cause vasodilation and natriuresis in an effort to return volume status back to normal. In patients with end-stage renal disease, the natriuretic capabilities of these peptides are limited. However, there has been much interest in the potential applicability of measurement of these peptides as a surrogate marker of volume status and in the determination of dry weight. Furthermore, atrial natriuretic peptide and brain natriuretic peptide can serve as markers of left ventricular dysfunction and may have utility in determining cardiac prognosis in patients on long-term dialysis therapy.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Body Weight; Cohort Studies; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptides; Peritoneal Dialysis; Prognosis; Rats; Receptors, Neuropeptide; Ventricular Dysfunction, Left; Water-Electrolyte Balance

The natriuretic peptides are hormones released mainly from the cardiac ventricles in response to increased wall tension, and involved in volume homeostasis and cardiovascular remodeling. At today, Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP) have been identified. BNP is the more utilized, secondary to its major expression of left ventricle function. Recently, it has opened up the potential for the utilization of atrial natriuretic peptides in the everyday clinical practice. The levels of B-type natriuretic peptide are elevated in patients with left ventricular dysfunction and they correlate with both the severity of symptoms and the prognosis. Observational studies have suggested that, when used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department may be useful in establishing or ruling out the diagnosis of heart failure in patients with acute dyspnea. Furthermore, plasma peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors. BNP has been studied also in myocardial ischemia: in ST-segment elevation myocardial infarction, BNP rise substantially and rapidly. Elevated levels of BNP can also be detected in patients presenting with non-ST-segment elevation acute coronary syndromes, and even in those with transient myocardial ischemia exercise-induced.

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Ventricular Dysfunction, Left

Topics: Apoptosis; Biomarkers; Heart Failure; Hepatocyte Growth Factor; Humans; Natriuretic Peptide, Brain; Prognosis; Risk Assessment

Cardiac secretion of B-type natriuretic peptide (BNP) Increases with the progression of heart failure (HF), and plasma measurement of BNP has emerged recently as a useful, cost-effective biomarker for the diagnosis and prognosis of HF. The diagnostic utility of BNP is complemented by its therapeutic use in decompensated HF. Although clinical use of BNP as a biomarker in HF is Increasing, the specificity of BNP for HF is not robust, suggesting that other mechanisms beyond simple ventricular stretch stimulate BNP release. Several studies have shown that BNP levels Increase in other cardiovascular disease states including ischemia, arrhythmias, fibrosis, cardiac hypertrophy, and coronary endothelial dysfunction. Furthermore, 2 important studies revealed recently that moderate elevations In BNP level, well below the HF range, have prognostic value for future cardiovascular events. Specifically, BNP levels greater than 20 pg/mL were associated with significantly Increased risk of HF and atrial fibrillation. These observations increase speculation that elevated BNP levels represent a final common pathway for many cardiovascular pathologic states and that BNP can be used as a biomarker for non-HF mechanisms, preclinical disease, and other pathologic states of myocardial disease.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis

Congestive heart failure remains a severe condition. Risk stratification is necessary to assess the prognosis and discuss the potential timing of heart transplant. Numerous criteria have been used, which may be combined to define prognostic scores which, however, are rarely used in routine. A few items, however, may be used to stratify the risk of mortality and sudden death.

Topics: Coronary Angiography; Echocardiography; Heart Failure; Humans; Hypertension; Liver Failure; Natriuretic Peptide, Brain; Oxygen Consumption; Renal Insufficiency; Risk Assessment; Stroke Volume

The recent guidelines of the European Society of Cardiology, recommends laboratory testing as an essential part of the evaluation of the patient presenting with acute or chronic heart failure. The decrease in BNP has been included as a treatment goal for the management of acute heart failure. As for other properties it is important to define what difference can be considered as a real change of the marker in serial measurements. Therefore, knowledge of pathophysiological influences and pre-analytical issues as well as the intraindividual variability of BNP and N-terminal proBNP (NT-proBNP) due to analytical imprecision and biological variation is crucial. Erroneous test results with BNP or NT-proBNP assays are rare but may occasionally occur analytical interferences and should be suspected if the results do not suit the clinical picture or the serial kinetics. Although BNP assays correlate closely, due to lack of standardization no two BNP assays are analytically equivalent, and the same assay must be used for serial measurement. The in-vitro stabilities of BNP and NT-proBNP are sufficient for routine use, and blood sampling for BNP or NT-proBNP directly after arrival without a standardized period of rest is feasible, however, heavy physical exercise should be avoided before blood sampling. To be on the safe side a period of 10 minutes rest before blood sampling is recommended. BNP and NT-proBNP are suitable for heart failure monitoring, and BNP and NT-proBNP changes >50% from baseline correlated well with clinical course and a reduction of mortality in heart failure patients.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spironolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guidance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.

Topics: Algorithms; Cardiotonic Agents; Decision Making, Computer-Assisted; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnostic Techniques, Endocrine; Heart Failure; Humans; Hypertension; Hyperthyroidism; Immunoradiometric Assay; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Reference Values; Specimen Handling; Tachycardia, Supraventricular

Bedside dosage of B-type natriuretic peptide as a marker of congestive heart failure is of major interest in the evaluation of acute dyspnea. However, this test remains difficult to use because its interpretation depends upon the probability of disease and upon its diagnostic performance (sensitivity and specificity), varying with each BNP level. When the clinical probability of heart failure is low or high, BNP level doest not modify significantly the probability of disease. The test is useful when the diagnostic is uncertain (intermediate clinical probability), because a BNP value < 100 pg/ml makes the diagnosis of heart failure unlikely (high negative predictive value), and a value > 500 pg/ml very likely.

Topics: Biomarkers; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity

Heart failure is analysed following the recent classification (prognostic and symptomatic: 4 stages) proposed by the American Heart Association (AHA). The study is focused on the first stage (Stage A) of the AHA classification where the patient is asymptomatic, without heart structural abnormalities but at risk to develop heart failure. In Stage A neurohumural mechanisms of heart failure such as natriuretic peptide system are activated. The author analyses the links between heart failure and the natriuretic peptide system and the role played by the plasma level of brain natriuretic peptide as biomarker of heart failure in Stage A.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain

The lack of large randomised controlled trials to guide therapy in diastolic heart failure causes some difficulties for evidence-based medicine practising clinicians. Traditionally, treatments for systolic heart failure have been highjacked for diastolic heart failure without much proof of benefit. However, recent studies have began to provide some evidence base for our practice. Betablockers and angiotensin receptor antagonists have recently been shown to reduce hospitalisation in large randomised controlled trials. Diuretic based antihypertensive regimes have been shown to reduce heart failure by 50%. Left ventricular hypertrophy regression is likely to be a good surrogate endpoint for diastolic heart failure, although definitive proof for this is not yet available. Angiotensin receptor antagonists, ACEI, calcium channel blockers, diuretics and aldosterone blockers have all been shown to cause left ventricular hypertrophy regression. We recommend these drugs to achieve strict blood pressure control together with dietary and lifestyle modification for the treatment of diastolic heart failure. We emphasise the importance of rate control, as diastolic heart-failure patients tolerate tachycardia poorly. We further argue that the pathophysiology of diastolic heart failure is part of systolic heart failure and the two should not be thought of as separate entities. Therefore, our traditional practice of using systolic heart failure treatments for diastolic heart failure is theoretically sound and should not cause us undue anxiety.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Diastole; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Natriuretic Peptide, Brain; Treatment Outcome

To review current issues in the management of acute decompensated heart failure (ADHF), focusing on the early initiation of intravenous (i.v.) vasoactive therapy and including the effects of vasoactive drugs on patient outcomes and the benefits and limitations of each medication class.. Review of the worldwide scientific literature on ADHF.. The management of ADHF may be improved by early initiation of i.v. vasoactive therapy, reduced use of inotropic agents, and judicious use of diuretics. Data to date suggest that early treatment with the natriuretic peptide nesiritide reduces duration of hospitalization, in-hospital mortality, and requirements for i.v. inotropes and diuretics.. Advance practice nurses play an integral role in the management of patients with ADHF from initial triage in the emergency department through final discharge from the hospital. Because they are typically responsible for administering medications and monitoring patient status, nurses need to be familiar with the benefits and limitations of each class of vasoactive agent. They need to recognize that prompt initiation of i.v. vasodilator therapy is important for improving patient outcomes. Further, advance practice nurses should participate in team management that promotes the use of evidence-based ADHF care by developing, using, and assertively communicating the need for processes of care that facilitate best practices.

Topics: Cardiotonic Agents; Diuretics; Drug Administration Schedule; Drug Therapy, Combination; Heart Failure; Hospital Mortality; Humans; Infusions, Intravenous; Natriuretic Agents; Natriuretic Peptide, Brain; Nurse Practitioners; Outcome and Process Assessment, Health Care; Registries; Time Factors

Advanced heart failure (HF) is associated with frequent hospitalizations, poor quality of life, and increased mortality. Despite optimal medical management, readmission rates remain high and account for approximately two thirds of all costs related to HF management. Evaluation of patients with HF is critical for the appropriate selection and monitoring of therapy as well as for the prevention of recurrent hospitalizations. This evaluation can be complex and relies on integration of the bedside evaluation and information available from invasive and other noninvasive diagnostic techniques. The clinical examination remains the cornerstone of HF evaluation. Key features of the history and physical examination can be used to assign hemodynamic profiles based on the absence or presence of congestion and adequacy of perfusion. These hemodynamic profiles provide prognostic information and may be used to guide therapy. Direct measurement of hemodynamics may be helpful in patients in whom the physical examination is limited or discordant with symptoms. Although the pulmonary artery catheter (PAC) is not recommended during routine therapy of patients hospitalized with HF, it is reasonable to consider the use of PAC monitoring to adjust therapy in patients who demonstrate recurrent or refractory symptoms despite ongoing standard therapy adjusted according to clinical assessment. This is particularly relevant in centers with experience in hemodynamic monitoring for HF. B-type natriuretic peptide (BNP) testing has been shown to facilitate diagnosis of the etiology of dyspnea in the urgent setting for patients without a prior diagnosis of HF. Furthermore, BNP levels provide important prognostic information in patients with chronic HF, but serial BNP testing has not been validated as a guide to inpatient or outpatient management. Echocardiographic assessment can provide prognostic information about ventricular function and size as well as information about hemodynamic status. Development of validated and reproducible noninvasive techniques to monitor patients with acute HF will be an important step in maximizing interventions to improve outcomes in this patient population.

Topics: Acute Disease; Catheterization, Swan-Ganz; Echocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain; Physical Examination; Syndrome

Several treatment strategies exist for patients hospitalized with acute heart failure syndromes (AHFS). These therapies traditionally focus on improving hemodynamics and relieving congestion. This review focuses on noninodilator therapies, including diuretics, nitrovasodilators (nitroprusside and nitroglycerin), vasodilators (nesiritide), digoxin, and intravenous angiotensin-converting enzyme inhibitors. These agents are used based on their associated symptomatic improvements alone. In the hospitalized setting, none of these agents have demonstrated benefits on long-term outcomes. Future work in AHFS should strive to understand the influence of conventional and new pharmacologic therapies on the underlying pathophysiology of AHFS, the processes that lead to myocardial injury and progressive heart failure, and measurable clinical outcomes.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Severity of Illness Index; Syndrome; Vasodilator Agents

Heart failure is a disease of epidemic proportions. Almost five million Americans suffer from heart failure and over 400,000 patients are newly diagnosed with heart failure each year. Indeed, heart failure is now the only cardiovascular disease that is increasing in incidence and prevalence. Costs related to heart failure are $18.8 billion per year and are steadily increasing. Although the outpatient management of these patients has seen substantial improvement in the last two decades, emergency department (ED) treatment of acute decompensated heart failure has remained largely unchanged since the late 1970s. Current ED therapy consists of diuretics, intravenous vasodilatators, and inotropes. Recently, the outcomes of several high-profile clinical trials evaluating intravenous nesiritide (human B-type natriuretic peptide) have suggested a benefit in select hospitalized patients. Such a therapy has potential to provide a therapeutic addition or alternative for emergency heart failure management. We discuss these trials' results, suggest their relationship to the ED population, and provide recommendations for appropriate ED use.

Topics: Cardiotonic Agents; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Randomized Controlled Trials as Topic; Treatment Outcome; Vasodilator Agents; Ventricular Premature Complexes

Topics: Acute Disease; Adult; Age Factors; Aged; Confounding Factors, Epidemiologic; Female; Forecasting; Heart Failure; Humans; Immunoassay; Luminescent Measurements; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Risk Assessment; Sensitivity and Specificity; Sex Factors

Dyspnea is a common complaint in the emergency department where physicians must accurately make a rapid diagnosis.. To assess the usefulness of history, symptoms, and signs along with routine diagnostic studies (chest radiograph, electrocardiogram, and serum B-type natriuretic peptide [BNP]) that differentiate heart failure from other causes of dyspnea in the emergency department.. We searched MEDLINE (1966-July 2005) and the reference lists from retrieved articles, previous reviews, and physical examination textbooks.. We retained 22 studies of various findings for diagnosing heart failure in adult patients presenting with dyspnea to the emergency department.. Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality.. Many features increased the probability of heart failure, with the best feature for each category being the presence of (1) past history of heart failure (positive LR = 5.8; 95% confidence interval [CI], 4.1-8.0); (2) the symptom of paroxysmal nocturnal dyspnea (positive LR = 2.6; 95% CI, 1.5-4.5); (3) the sign of the third heart sound (S(3)) gallop (positive LR = 11; 95% CI, 4.9-25.0); (4) the chest radiograph showing pulmonary venous congestion (positive LR = 12.0; 95% CI, 6.8-21.0); and (5) electrocardiogram showing atrial fibrillation (positive LR = 3.8; 95% CI, 1.7-8.8). The features that best decreased the probability of heart failure were the absence of (1) past history of heart failure (negative LR = 0.45; 95% CI, 0.38-0.53); (2) the symptom of dyspnea on exertion (negative LR = 0.48; 95% CI, 0.35-0.67); (3) rales (negative LR = 0.51; 95% CI, 0.37-0.70); (4) the chest radiograph showing cardiomegaly (negative LR = 0.33; 95% CI, 0.23-0.48); and (5) any electrocardiogram abnormality (negative LR = 0.64; 95% CI, 0.47-0.88). A low serum BNP proved to be the most useful test (serum B-type natriuretic peptide <100 pg/mL; negative LR = 0.11; 95% CI, 0.07-0.16).. For dyspneic adult emergency department patients, a directed history, physical examination, chest radiograph, and electrocardiography should be performed. If the suspicion of heart failure remains, obtaining a serum BNP level may be helpful, especially for excluding heart failure.

Topics: Adult; Aged; Diagnostic Techniques, Cardiovascular; Dyspnea; Electrocardiography; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Physical Examination; Radiography, Thoracic; Valsalva Maneuver

Heart failure (HF) is a common disorder that is associated with significant mortality and morbidity. However, the diagnosis of HF may at times be difficult when using conventional tools. The cardiac natriuretic peptides, particularly brain (B-type) natriuretic peptide (BNP), have evolved to be useful biomarkers of cardiac function and prognosis in HF and other cardiovascular disorders. Multiple observational studies have established the close association between plasma BNP as well as the N-terminal fragment of the BNP prohormone (NT-proBNP) with the diagnosis of HF and an independent prediction of mortality and HF events. Although there are confounding variables to consider, when used in the correct clinical settings, BNP or NT-proBNP testing can be extremely useful. Furthermore, preliminary data from randomized controlled trials suggest that knowledge of BNP and/or NT-proBNP level may optimize the management of patients with HF. Large-scale randomized controlled trials that evaluate BNP/NT-proBNP-guided therapy are ongoing.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Risk Assessment

Topics: Acute Disease; Algorithms; Biomarkers; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain

The heart is not only a pump, but also it is an endocrine organ. Cardiac stretch and overload stimulate the secretion of natriuretic peptides, which have a variety of beneficial actions, such as vasodilation and natriuresis. Cardiac-derived natriuretic peptides, especially B-type natriuretic peptide (BNP), have emerged as useful biomarkers for the diagnosis, and potentially the treatment, of heart failure patients. The inactive amino-terminal fragment of the BNP prohormone (NT-proBNP), which is more stable than mature BNP, has also been recognized as an aid in the diagnosis of left-ventricular systolic dysfunction. Furthermore, elevated NT-proBNP concentrations have been shown to be predictive of poor prognosis in a variety of cardiovascular diseases, suggesting that it could be useful for risk stratification of patients. This review summarizes current literature that has addressed the issue of NT-proBNP as a prognostic tool in heart failure, acute coronary syndromes and other conditions.

Topics: Acute Disease; Biomarkers; Coronary Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Syndrome; Systole; Ventricular Dysfunction, Left

Cardiovascular disease is the most common complication of type 2 diabetes mellitus (type 2 DM), accounting for approximately 80% of deaths. While atherosclerotic vascular disease accounts for much of the cardiovascular morbidity and mortality among diabetic patients, congestive heart failure (CHF) is another key complication associated with diabetes, with an incidence three to five times greater in diabetic patients than in those without diabetes. One of the most promising developments in the treatment of type 2 DM has been the introduction of the thiazolidinedione (TZD) class of drugs, which appear to have pleiotropic effects beyond glycaemic control. Enthusiasm has been tempered, however, by concerns for safety in patients with CHF, given reports of worsening heart failure symptoms and peripheral oedema. With the growing epidemic of type 2 DM and the increasing use of TZDs, such concern has important therapeutic implications for a population of patients with a high prevalence of often subclinical systolic and diastolic dysfunction. This review provides an overview of the currently available data regarding the effects of TZDs on fluid retention and cardiac function. Particular emphasis is placed on the mechanisms of development of peripheral oedema and its significance in patients with impaired left ventricular function. TZDs are well known to cause an expansion in plasma volume; there has also been concern that TZDs may have direct toxic effects on the myocardium, leading to impaired cardiac function. Studies to date do not support this hypothesis and in fact there is growing evidence from animal models and human trials that treatment with TZDs actually improves cardiac function. There are also preclinical data to suggest TZDs may protect the myocardium in the setting of ischaemic insult or the toxic effects of myocardial lipid deposition. Ongoing clinical trials examining the use of these agents in patients at risk for heart failure will probably provide further insight into the aggregate cardiovascular effects of this promising class of medications.

Topics: Animals; Body Fluids; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Edema; Endothelium, Vascular; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Infarction; Myocytes, Cardiac; Natriuretic Peptide, Brain; PPAR gamma; Practice Guidelines as Topic; Thiazolidinediones; Triglycerides; Ventricular Dysfunction, Left

Topics: Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Catheterization; Cardiac Volume; Controlled Clinical Trials as Topic; Diagnosis, Differential; Diastole; Diuretics; Echocardiography; Echocardiography, Doppler; Female; Heart Failure; Heart Rate; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Physicians, Family; Prognosis; Prospective Studies; Ventricular Dysfunction, Left

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

Natriuretic peptide type B (brain natriuretic peptide, BNP) is a neurohormone released by cardiac ventricles in response to volume and pressure load. Recent studies have demonstrated that BNP level measured in the plasma plays an important role in cardiovascular diseases especially in the diagnosis and treatment of heart failure and acute coronary syndrome. This article summarizes the physiology of the brain natriuretic peptide, diagnosis of heart failure and acute coronary syndrome and use of BNP in the treatment and determining the prognosis of cardiovascular diseases.

Topics: Cardiovascular Diseases; Coronary Disease; Heart Failure; Humans; Natriuretic Peptide, Brain

Heart failure (HF) is a clinical syndrome that occurs when the ability of the heart to meet the requirements of the body fails. Myocardial infarction (MI) is a common antecedent event that predisposes a patient to HF. Loss of cardiac function following MI occurs in the context of myocyte death and ventricular remodeling. The clinical significance of HF following MI is underscored by the fact that among MI survivors, the risk of death is markedly elevated in those who develop HF compared with those who do not. Various modifying factors associated with the development of HF following MI have been identified. Use of multimodality therapy with improved clinical outcomes for HF has increased the need to specifically identify the failing heart at an earlier stage. The ability to identify heart failure early in its pathogenesis will enable finer risk stratification following MI. This article reviews various risk predictors for the development of HF following MI.

Topics: Biomarkers; Cytokines; Echocardiography; Exercise Test; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Stroke Volume; Troponin

B-type natriuretic peptide (BNP) is an endogenous cardiac neurohormone, produced in the ventricles in response to pressure and volume elevation. Nesiritide is identical to endogenous BNP and is synthesized using recombinant DNA technology. It is currently used in the treatment of acute decompensated heart failure. In clinical trials, nesiritide has been shown to decrease pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance, as well as increase cardiac index and stroke volume index. Infusions of nesiritide have led to increased diuresis and natriuresis. Patients treated with nesiritide have reported improvements in global clinical status, dyspnea, and fatigue. Therapy with nesiritide has resulted in decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels, as well as reduced ventricular ectopy and ventricular tachycardia. Heart rate variability also improved with nesiritide. Patients with acute coronary syndromes, serious arrhythmia, renal disease, diastolic dysfunction, or vasopressor dependence have been safely managed with nesiritide. Early treatment with nesiritide in the emergency department may lead to decreased length of hospital stay and reduced readmission rates compared to standard care. Outpatient serial infusions of nesiritide in severe heart failure patients on optimal medical therapy may result in improved clinical status, increased ejection fraction, reduced aldosterone and endothelin-1 levels, and decreased hospitalizations. Potential future uses of nesiritide include treatment of acute coronary syndromes, pulmonary hypertension, bronchospasm in chronic lung disease, and as antifibrotic/anti-remodeling therapy or bridge to cardiac transplant. The possibility of subcutaneous injections of nesiritide has been studied in both animals and humans.

Topics: Animals; Clinical Trials as Topic; Forecasting; Heart Failure; Humans; Injections, Intravenous; Natriuretic Agents; Natriuretic Peptide, Brain

Heart failure (HF) is one of the leading cardiovascular health problems in Europe and the United States. Acute decompensated HF remains a lethal diagnosis with a morbidity and mortality that often exceeds neoplastic or infective diseases. The incidence of HF continues to increase despite an intensive effort to increase education and delivery of healthcare to these affected patients. Yet, current guidelines in the United States do not address the management of acute decompensated HF, and focus predominantly on chronic stable systolic HF as well as patients with left ventricular dysfunction. Although the European Society of Cardiology has established some parameters for the management of acute HF, these guidelines are largely established by expert opinion, and are predominantly devoid of prospective randomized data in this cohort of patients. Current pharmacotherapies for acute decompensated HF include diuretics, neurohormonal antagonists, vasodilators, and inotropes. Regrettably, all of these drugs have their limitations in acute HF. Neurohormonal antagonists reduce morbidity and mortality, but may be inadequate to achieve and maintain the necessary hemodynamic relief required in advanced HF; while, bolus diuretics, a mainstay of initial symptomatic relief, may be maladaptive and up-regulate adverse neurohormonal regulatory mechanisms longterm with no positive impact on longterm mortality. Today, for those advanced HF patients who remain symptomatic despite optimal conventional therapy, limited treatments exist; but as newer therapies evolve, the options will expand to include more than palliative care, heart transplant and ventricular assist devices for these patients.

Topics: Acute Disease; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Pacing, Artificial; Cardiotonic Agents; Diuretics; Drug Therapy, Combination; Evidence-Based Medicine; Heart Failure; Heart Transplantation; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Risk Assessment; Vasodilator Agents

Cardiac failure is a prevalent and costly condition in Western society. The ageing of the population, together with current medical options which improve, rather than eradicate heart failure, lead to the projection that this problem will increase substantially in the foreseeable future. The availability of a simple test to assist the diagnosis and effective management of heart failure would greatly assist the clinical approach to this problem. This review examines the physiological basis for the measurement of natriuretic peptides as markers of the presence or risk of heart failure. It considers its use in the hospital and non-hospital setting and examines the cost-effectiveness of current assays. It is possible that in future natriuretic peptides may offer a form of treatment for heart failure, but this is beyond the scope of this review. Nevertheless, the review highlights the potential benefits of this group of tests in the management of heart failure.

Topics: Biomarkers; Cost-Benefit Analysis; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis

Topics: Aldosterone; Animals; Cardiotonic Agents; Disease Progression; Dose-Response Relationship, Drug; Endomyocardial Fibrosis; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Sodium; Treatment Outcome; Ventricular Remodeling

B-type natriuretic peptide is a neurohormone secreted from the cardiac ventricles in response to ventricular stretch and pressure overload. It counteracts the vasoconstriction that occurs as a compensatory mechanism in heart failure. A new test for measuring plasma levels of B-type natriuretic peptide can help in the diagnosis and treatment of patients with congestive heart failure. Dyspnea associated with cardiac dysfunction is highly unlikely in patients with levels of the peptide less than 100 pg/mL. Whereas most patients with significant congestive heart failure have levels of the peptide greater than 400 pg/mL, in patients with levels of 100 to 400 pg/mL, left ventricular dysfunction without volume overload, pulmonary embolism, and cor pulmonale must be ruled out. Thus, incorporating measurement of B-type natriuretic peptide into clinical evaluation helps physicians and nurses diagnose heart failure more quickly, especially in patients who have multiple comorbid conditions. Elevated levels of B-type natriuretic peptide indicate a poor prognosis in terms of a higher mortality and more hospital readmissions. Levels of B-type natriuretic peptide could be used to guide therapy and discharge planning for patients admitted with decompensated heart failure.

Topics: Dyspnea; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Radioimmunoassay

Brain natriuretic peptide (BNP), also called B-type natriuretic peptide, is a member of a family of structurally related hormones, the natriuretic peptides. Current data suggest that measurement of BNP plasma concentrations is a useful tool in the diagnosis of acute heart failure in patients presenting to an emergency department with acute dyspnea. Furthermore, BNP constitutes a promising new marker of prognosis after an acute coronary syndrome episode and in patients with chronic heart failure. Nesiritide, the human recombinant form of BNP, is a new vasodilator used in the treatment of acute heart failure that has several potential advantages over current drug therapy.

Topics: Adult; Aged; Biomarkers; Critical Illness; Emergency Treatment; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome; Ventricular Remodeling

Determining whether a patient's symptoms are the result of heart or lung disease requires an understanding of the influence of pulmonary venous hypertension on lung function. Herein, we describe the effects of acute and chronic elevations of pulmonary venous pressure on the mechanical and gas-exchanging properties of the lung. The mechanisms responsible for various symptoms of congestive heart failure are described, and the significance of sleep-disordered breathing in patients with heart disease is considered. While the initial clinical evaluation of patients with dyspnea is imprecise, measurement of B-type natriuretic peptide levels may prove useful in this setting.

Topics: Adult; Aged; Biomarkers; Biopsy, Needle; Diagnosis, Differential; Dyspnea; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension, Pulmonary; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema; Radiography, Thoracic; Respiratory Function Tests; Risk Assessment; Severity of Illness Index

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Receptors, Atrial Natriuretic Factor

Many patients with heart failure have stiff hearts with an increased wall thickness and small volumes leading to diastolic dysfunction. Different definitions for diastolic heart failure have been proposed but today there is no generally accepted definition and there are few large controlled studies telling us how it should be managed. Natriuretic peptides (BNP or NT-proBNP) might be used to detect patients with diastolic dysfunction especially in those patients having a restrictive filling pattern or pseudo-normalised mitral flow pattern and in those, who are symptomatic. However, patients with relaxation abnormalities and mild symptoms or asymptomatic may have normal levels of the natriuretic peptides indicating no or only slight elevation of the left ventricular filling pressures. Thus low levels cannot be used as a rule out diagnosis of diastolic dysfunction.

Topics: Aged; Aged, 80 and over; Diastole; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

With increasing cardiac dysfunction, a complex neurohormonal response results in increasing circulating levels of an array of plasma hormones. Increments in plasma levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) and their amino-terminal congeners are more closely related to cardiac structure and function and to cardiovascular prognosis than changes in other plasma neurohormones. Reports suggest that changes in plasma BNP levels in the course of treatment of acutely decompensated heart failure provide a more powerful prognostic indicator of the likelihood of survival or recurrent decompensation than symptomatic assessment. This observation requires a randomised controlled trial in which changes in peptide levels determine aggression and duration of in-patient therapy in order to establish whether this indicator can improve results from management of acute in-patient heart failure. Plasma BNP or NT-proBNP is a powerful independent predictor of mortality and morbidity in long-term follow-up of heart failure cohorts. In addition, it appears likely to be a good predictor of beneficial response to the addition of beta blockade to anti-heart failure pharmacotherapy. Finally, adjustment of therapy for heart failure according to serial measurements of NT-proBNP promises to improve outcomes in comparison with adjusting therapy according to unassisted clinical acumen.

Topics: Biomarkers; Cardiovascular Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome

B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence).. We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers.. While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value.. Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.

Topics: Biomarkers; Heart Failure; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index; Time Factors

Topics: Diabetes Complications; Diabetes Mellitus; Heart Failure; Humans; Hypoglycemic Agents; Natriuretic Peptide, Brain; Thiazolidinediones

Topics: Biomarkers; Critical Pathways; Emergency Service, Hospital; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Care Planning

Topics: Algorithms; Biomarkers; Case Management; Exercise; Heart Failure; Humans; Natriuretic Peptide, Brain; Quality of Life

Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure.

Topics: Animals; Comorbidity; Heart Failure; Hemodynamics; Humans; Kidney; Kidney Failure, Chronic; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Regional Blood Flow

As there is no cure in Duchenne muscular dystrophy (DMD), we must pay attention to the management of its cardiopulmonary complications. In 1984, DMD patients died at the mean age of 18.2 years in my hospital. From autopsy findings, the cause of death was respiratory failure in 75% of them, and left-sided heart failure 12.5%. First, we had to know the relationship between cardiac and respiratory systems. Based on the findings of right-sided heart catheterization, patients with respiratory failure were classified into Forrester's subset 1' normal left ventricular function. These results showed that these patients require treatment with a respirator, but not with digitalis and/or diuretics. Since 1984, we tried cuirass ventilation, which prolonged their lives by about 3 years. Since 1991, NIPPV was introduced in Japan, and prolonged their lives by about 5.5 years. Nowadays TIPPV with tracheostomy is not the first choice of treatment, but we do not hesitate to select this treatment any more. As for left-sided heart failure, brain natriuretic peptide (BNP) is now considered a useful parameter of left ventricular function. Japanese clinical researcher proposed treatment based on values of BNP in left-sided heart failure. In 1980s, the mean interval from the onset of heart failure to death was only 16 months. Recently we feel that better results have already been accomplished. In 2002 Kawai reported that average age at death in Japan was 26.8 years old. More efforts must be made until cure of this disease is found.

Topics: Biomarkers; Heart Failure; Humans; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain; Positive-Pressure Respiration; Respiratory Insufficiency; Stroke Volume; Survival Rate

B-type natriuretic peptide is a neurohormone synthesized in the cardiac ventricles upon ventricular pressure overload and ventricular dilatation. This peptide with many favourable physiological properties has emerged as important candidate for development of diagnosis and prognostic tools and therapeutic agents in cardiovascular disease.. Literature published until now shows the interest to measure B-type natriuretic peptide in the diagnosis of ventricular dysfunction or congestive heart failure. B-type natriuretic peptide is also a prognostic marker in patients with congestive heart failure and acute coronary syndrome. It could even help to guide patient treatment management. It is easily and rapidly measured at a reasonable cost. In general, a level less than 50 ng/l has a strong negative predictive value for congestive heart failure.. B-type natriuretic peptide is available in daily clinical practice. Future interest has focused on development of drugs that modulate its effects in treatment of decompensated congestive heart failure. Studies are in progress and first results seem to be promising.

Topics: Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Reference Values

In spite of its high prevalence and the huge burden it imposes on health care systems, heart failure is a clinical syndrome that has not yet been defined satisfactorily. In actual practice, diagnosis requires the presence of typical signs and symptoms along with data from complementary tests that indicate definite cardiac dysfunction. In this article we review current concepts of the disease, stages of development, common underlying causes, and the value of different diagnostic tests. Among these tests, measurement of B-type natriuretic peptide has proved useful for population screening and the differential diagnosis of heart failure. This indicator seems to be the ideal link between the large population of patients in whom heart failure is suspected and the subgroup for whom cardiac ultrasound, the most informative test in this disease, is warranted.

Topics: Clinical Trials as Topic; Coronary Angiography; Echocardiography; Electrocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Diuretics; Drug Therapy, Combination; Eplerenone; Heart Failure; Humans; Hydrazones; Natriuretic Agents; Natriuretic Peptide, Brain; Neurotransmitter Agents; Pyridazines; Simendan; Spironolactone; Treatment Outcome; United States

Heart failure has reached epidemic proportions and the prevalence is increasing. The accurate and efficient diagnosis of heart failure remains problematic, as signs and symptoms are neither sensitive nor specific. Recent advances in the diagnosis of this condition include a conceptual change in what constitutes heart failure, a greater understanding of heart failure with preserved systolic function, and an abundance of data supporting the use of neurohormonal assays, particularly brain-type natriuretic peptide. These factors will help facilitate earlier diagnosis and targeted treatment of patients with this malady.

Topics: Biomarkers; Diagnostic Techniques, Cardiovascular; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Severity of Illness Index

Acute decompensated heart failure represents a major, growing health problem in the developed world. However, until recently, relatively little research has been performed in this field to provide a basis for rational treatment strategies. The purpose of this review is to discuss the current approach and the potential future strategies for treatment of patients with acute decompensated heart failure.. Recent data have confirmed the heterogeneous nature of patients admitted with acute decompensated heart failure, and the limitations of the current therapeutic regimens with diuretics, intravenous vasodilators (ie, nitroglycerin, nitroprusside), and intravenous inotropes (ie, dobutamine, milrinone). A new vasodilator, nesiritide, has been demonstrated to improve hemodynamics and symptoms at 3 hours compared with nitroglycerin, and has been added to the therapeutic armamentarium in the United States. However, none of these agents has been shown to influence patient outcomes favorably. Given the high readmission rates, morbidity, and mortality of acute decompensated heart failure, other newer approaches, such as antagonists to a number of neurohumoral targets (ie, endothelin [tezosentan], vasopressin [conivaptan, tolvaptan], and adenosine) and non-cAMP-mediated inotropy (ie, levosimendan), are currently under investigation and showing promise.. Acute decompensated heart failure presents a challenging therapeutic problem for clinicians. Although they readily correct the hemodynamic abnormalities, current treatment strategies have significant limitations and have not been shown to improve morbidity or mortality. A number of new agents are under investigation with the goal of improving patient outcomes.

Topics: Acute Disease; Adenosine; Cardiotonic Agents; Catheterization, Swan-Ganz; Dobutamine; Drug Therapy; Endothelins; Forecasting; Heart Failure; Humans; Milrinone; Natriuretic Peptide, Brain; Vasopressins

Nesiritide (Natrecor) is a recombinant form of the human B-type natriuretic peptide (BNP) that has been shown, through several studies, to have beneficial natriuretic, diuretic and vasodilatory effects in the treatment of congestive heart failure (CHF). Nesiritide mimics the actions of endogenous BNP by binding to and stimulating receptors in the heart, kidney and vasculature. Nesiritide functions as both a potent venous and arterial vasodilator and has been shown to improve cardiac haemodynamics more rapidly and to a greater extent than intravenous nitroglycerin, as well as having fewer side effects. When compared in an open-label trial, nesiritide has also been shown to be less proarrhythmic than dobutamine. The major adverse effect of nesiritide, as with other vasodilators, is symptomatic hypotension, which occurred infrequently in clinical trials. Overall, nesiritide represents an effective and safe therapeutic option for the treatment of decompensated CHF.

Topics: Diuretics; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Vasodilator Agents

Chronic heart failure secondary to ventricular dysfunction is characterized by neurohormonal activation, reflected mainly as increased sympathetic and renin-angiotensin system activation. Increased plasma levels of several neurohormones have been associated with increased morbidity and mortality. Neurohormone activation is part of the mechanism of compensation that is activated to maintain hemodynamic stability when heart output is reduced. Despite the initial benefits of this mechanism, neurohormone activation has been shown to contribute to progressive impairment of ventricular function and symptoms of heart failure, such that the greater the degree of activation, the worse the prognosis.Despite their important implications for prognosis, plasma neurohormone levels are not measured in clinical practice as part of the clinical evaluation of patients with heart failure. Medical treatment with ACE inhibitors and beta blockers, by lowering the plasma levels of some neurohormones, reduces their prognostic usefulness in establishing risk. Thus, no ideal biomarker is yet available that is stable and easy to measure, and that accurately established risk in patients with heart failure. Such a marker should also have an acceptable cost/benefit ratio.

Topics: Angiotensin II; Atrial Natriuretic Factor; Biomarkers; Endothelins; Heart Failure; Humans; Interleukin-6; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Renin; Tumor Necrosis Factor-alpha

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted by the heart and play important roles in the compensation of congestive heart failure with their vasodilating, natriuretic, antiproliferative, lusitropic and neurohumoral-modulating properties. Based on these beneficial properties, exogenous BNP was developed as a new treatment for congestive heart failure and approved in the US for acute decompensated heart failure. New therapeutic strategies for heart failure that are currently being investigated include chronic subcutaneous BNP administration and intermittent BNP infusions. Furthermore, strategies combining exogenous BNP with an inhibitor of the BNP-degrading enzyme neutral endopeptidase could contribute to maximising the actions of BNP and reduce the amount of exogenous BNP needed.

Topics: Atrial Natriuretic Factor; Enzyme Activation; Guanylate Cyclase; Heart Failure; Humans; Kidney; Myocardium; Natriuresis; Natriuretic Peptide, Brain

Natriuretic peptide hormones are a family of vasoactive peptides with many favorable physiological properties and have emerged as useful markers in cardiovascular disease. In particular, brain natriuretic peptide (BNP) is a cardiac neurohormone secreted by the cardiac ventricles as a response to ventricular volume expansion, pressure overload and resultant increased wall tension, directly correlated with both left ventricular filling and pulmonary wedge pressure. It is nowadays considered an important diagnostic tool, adding information to clinical judgment in the evaluation of patients with acute dyspnea, and a useful guide to the treatment of chronic heart failure. Moreover, the prognostic value of BNP has been established in several studies, both in postmyocardial infarction patients with asymptomatic left ventricular dysfunction and in patients with overt heart failure. Furthermore it has been shown that BNP could also predict sudden death and offer an additive and easily obtainable tool for risk stratification of patients with chronic heart failure. This paper summarizes the current evidence concerning the use of this peptide in a variety of clinical scenarios.

Topics: Acute Disease; Algorithms; Angina, Unstable; Biomarkers; Diagnosis, Differential; Diastole; Dyspnea; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Syndrome; Ventricular Dysfunction, Left

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

Activation of the naturiuretic peptide system is a hallmark of heart failure (HF). In this paper the authors review aspects of the structure, regulation and physiology of the natriuretic peptides. The role of natriuretic peptides in HF progression is discussed. Potential clinical applications of BNP include diagnostic and prognosis in HF and myocardial infarction, as well as therapeutic monitoring of HF patients. Finally we review the therapeutic use of BNP.

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

MODALITIES FOR THE DIAGNOSIS OF VENOUS THROMBOEMBOLISM: Currently rely on the confrontation of the initial clinical data and the results of D-dimer measurements, a venous Doppler, although reliable, is not a first-line exploration. REGARDING TREATMENT: Indications for thrombolysis are currently limited to massive pulmonary oedema with shock. Alteplase added to heparin improves the progression of severe embolism; it spares the patients from heavy interventions of resuscitation but the mortality remains the same. Concerning anticoagulant treatments, prolonged antivitamin K at classical doses is more effective than low doses and for limited duration if phlebitis is an idiopathic one. FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION: Treatment of these heart failures, formerly know as 'diastolic' is similar to that of the acute phase of systolic heart failure. However, care should be taken with vasodilatators. CONCERNING HEART FAILURE IN GENERAL: The brain natriuretic peptide (BNP) represents a remarkable progress for the aetiological diagnosis of dyspnoea (inferior to 80 pg/ml in the case of pulmonary origin, superior to 300 pg/ml in the case of cardiac origin or severe pulmonary embolism). Regarding treatment, for acute heart failure, it is still the association of nitrates and diuretics, with oxygen therapy and eventually inotropics. Beta-blockers, which have revolutionized the treatment of chronic heart failure, must be maintained whenever possible in the case of the onset of acute pulmonary oedema. Multisite pacing is increasingly used in refractory chronic heart failure. Implantable defibrillation has become common practice. Non-invasive ventilation (Bi or C-PAP) is interesting in acute cardiogenic pulmonary oedema. THE PREVENTIVE ROLE OF N ACETYL-CYSTEINE: N acetyl cysteine reduces the incidence of nephropathies induced by the radio contrast products in patients with chronic kidney failure. Combined with hydratation, it must be proposed the day before and on the day of the procedure in any patient with diabetes or kidney failure.

Topics: Acetylcysteine; Acute Disease; Adrenergic beta-Antagonists; Anticoagulants; Counterpulsation; Diastole; Diuretics; Echocardiography; Electric Countershock; Fibrin Fibrinogen Degradation Products; Fluid Therapy; Heart Failure; Hemofiltration; Heparin; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Pulmonary Edema; Thromboembolism; Tissue Plasminogen Activator; Treatment Outcome; Vasodilator Agents; Venous Thrombosis

To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD).. The traditional methods for assessing functional status including New York Heart Association (NYHA) class, exercise intolerance and quality of life were reviewed in relation to BNP measurements in patients with LVSD. A meta-analysis of four studies evaluating BNP levels versus exercise peak oxygen uptake or 6-minute walking distance showed a significant correlation, but a low R-value of -0.59. Studies using BNP levels for optimisation of heart failure therapy showed conflicting results concerning the correlation between the functional improvement and changes in BNP levels. Conflicting results were also found concerning the utility of BNP levels as a surrogate to predict efficacy of the various anti-congestive therapies on heart failure outcome.. The results of the studies examining BNP measurement as a surrogate for functional status and drug efficacy in patients with LVSD are conflicting. Further studies are necessary to settle the place of BNP measurement as surrogate marker for exercise tolerance, NYHA classification and in assessing efficacy of different interventions in the clinical trials.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Carbazoles; Carvedilol; Clinical Trials as Topic; Data Collection; Drug Administration Schedule; Enalapril; Exercise Test; Exercise Tolerance; Health Status; Heart Failure; Humans; Imidazolidines; Meta-Analysis as Topic; Metoprolol; Natriuretic Peptide, Brain; Propanolamines; Quality of Life; Statistics as Topic; Treatment Outcome; Ventricular Dysfunction, Left

This paper critically reviews the major drug types that are currently used in the management of acute cardiogenic pulmonary oedema. As decompensated heart failure becomes an increasingly common problem in emergency departments in the developed world, optimization of emergency drug therapy for these critically ill patients is essential. The evidence base for 'routine therapy' in the ED is considered. The review also briefly considers emerging pharmacological therapies that may have an impact on future management of cardiogenic pulmonary oedema.

Topics: Acute Disease; Analgesics, Opioid; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Critical Illness; Developed Countries; Diuretics; Emergency Service, Hospital; Emergency Treatment; Evidence-Based Medicine; Furosemide; Heart Failure; Humans; Hydrazones; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroprusside; Oxygen Inhalation Therapy; Patient Selection; Pulmonary Edema; Pyridazines; Pyridines; Simendan; Tetrazoles; Treatment Outcome; Vasodilator Agents

The natriuretic peptide family consists of at least 3 structurally similar peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Under normal conditions, ANP is synthesized by the atrium and released in response to atrial stretch. This peptide plays an important role in sodium and water homeostasis and is involved in cardiovascular function. In contrast, BNP is synthesized primarily by the ventricles, and its circulatory concentrations are significantly elevated in profound congestive heart failure (CHF). While both plasma levels of ANP and BNP have been found to be increased in patients with various heart diseases, the elevation in circulatory BNP correlates better than ANP with the severity of CHF. Therefore, plasma BNP has been suggested (and lately used) to aid in the accurate diagnosis of heart failure in patients admitted to the emergency room with symptoms of decompensated heart failure. Furthermore, circulatory BNP has been utilized as a prognostic marker in CHF as well as a hormone guide in the evaluation of the efficacy of the conventional treatment of this disease state. In light of the cardiovascular and renal effects of BNP, which most likely exceed those of ANP, the former has been used as a therapeutic agent for the treatment of patients with acute severe CHF. Intravenous infusion of BNP into patients with sustained ventricular dysfunction causes a balanced arterial and venous vasodilatation that has been shown to result in rapid reduction in ventricular filling pressure and reversal of heart failure symptoms, such as dyspnea and acute hemodynamic abnormalities. Thus, the goal of this article is to review the physiology and pathophysiology of natriuretic peptides and the potential use of their circulating levels for diagnosis and treatment of heart failure.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Endopeptidases; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Protease Inhibitors; Renin-Angiotensin System

The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

Topics: Acute Disease; Angina, Unstable; Biomarkers; Coronary Disease; Heart Failure; Humans; Inflammation; Myocardial Infarction; Natriuretic Peptide, Brain; Necrosis; Prognosis; Risk Assessment

A variety of community-based epidemiological studies have suggested that 30-50% of patients with heart failure symptoms appear to have preserved left ventricular (LV) systolic function when assessed by echocardiography or similar techniques suggesting 'diastolic heart failure' (DHF) as its cause. The prognosis of these patients is characterised by morbidity and mortality similar to, but less overt than, patients with systolic dysfunction. However, rates of readmission for symptom control are broadly similar in patients with DHF or in those with systolic impairment. Thus, there are many similarities in the portrayal of both systolic and DHF but equally; there are also many key differences. Certainly, while there are several successful therapies for patients with systolic heart failure, the management of patients with DHF is poorly defined. In this review, the gaps in current knowledge and practice, which is creating this therapeutic void will be addressed.

Topics: Anti-Arrhythmia Agents; Diastole; Diuretics; Echocardiography; Heart; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitrates; Radionuclide Imaging; Renin-Angiotensin System; Vasodilator Agents

Since the discovery of cardiac hormones almost 25 years ago, a vast amount of clinical research has identified the cardiac natriuretic peptides and their precursors as markers of heart failure. It even seems likely that the pro-B-type natriuretic peptide (proBNP)-derived peptides in plasma may become the most frequently measured peptides in the daily diagnosis and control of therapy. In contrast, the biochemistry of the peptides has received less attention.. Published data available on the National Library of Medicine (NLM) were used as the basis for the review.. This review shows that the present understanding of the biochemistry of peptides is far from complete. In particular, cellular synthesis, including posttranslational precursor maturation, is poorly understood. Moreover, elimination of the precursor fragments is unknown. Elucidation of the molecular heterogeneity of proBNP products will therefore contribute to the understanding of the endocrine heart and may also have important diagnostic consequences. Above all, the different proBNP-derived peptides may not always be equal markers of the same pathophysiologic processes. A different metabolism and peripheral elimination may also impose new and peptide-specific limitations for diagnostic use.. It is necessary to focus more on the biology of the proBNP-derived peptides. In turn, new insight into the biochemistry could pave the way for more sensitive and disease-specific assays in the clinical setting.

Topics: Amino Acid Sequence; Biomarkers; Heart Failure; Humans; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Sequence Alignment

Brain natriuretic peptide (BNP) is a cardiac neurohormone of increasing interest over recent years, with research applications expanding at a rapid rate and new data published on a monthly basis. Initially developed as a diagnostic aid for those with acute shortness of breath, clinical applications are now increasing, and this article reviews these clinical applications of BNP and the evidence for effectiveness of the synthetic BNP analogue nesiritide.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Adrenergic beta-Antagonists; Cardiac Pacing, Artificial; Heart Failure; Humans; Natriuretic Peptide, Brain

Elevated plasma brain natriuretic (BNP) concentrations correlate with increased cardiac filling pressures. Therefore, increased BNP has been proposed as a marker for asymptomatic ventricular dysfunction, as an aid in the diagnosis of cardiac dyspnea, as an end point to assess the efficacy of heart failure therapy, and as a prognostic marker in heart failure. An understanding of the utility of BNP requires an appreciation of the sensitivity, specificity, and diagnostic accuracy of BNP in each of these clinical situations. At this time, there is strong evidence for the value of BNP in the evaluation of dyspnea of uncertain cause. Further population studies will need to be performed to refine the application of BNP to community cohorts and to determine its clinical value and cost-effectiveness as a screening tool in the early diagnosis of ventricular dysfunction. To make optimal use of BNP for the assessment of heart failure therapy and prognosis in individual patients, physicians will require additional information on the biological variability of BNP. Studies comparing the sensitivity, specificity, and predictive value of the available BNP and N-terminal pro-BNP assays need to be conducted in each of these clinical settings.

Topics: Biomarkers; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Sensitivity and Specificity

Diagnosing or managing heart failure may still remain difficult. BNP and NT proBNP are neurohormones specifically secreted by myocytes. They have proved their effectiveness to improve clinician's diagnostic accuracy for diagnosing heart failure. BNP use is now recommended by European Society of Cardiology guidelines but multiplication of publications about BNP and NTProBNP show new possible applications for natriuretic peptides.

Topics: Acute Disease; Blood Chemical Analysis; Follow-Up Studies; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis

A growing body of literature describes diagnostic and prognostic value of B-type natriuretic peptides (BNP) in cardiac diseases since it was first described in 1988. As BNP is mainly secreted in the left ventricular (LV) myocardium, BNP was found to reflect LV function much better than any other neurohumoral factor. Thus, BNP is recommended as the first noninvasive blood test for determination of cardiac function by some authors. The introduction of fully automated, rapid bioassays for measurement of BNP and the aminoterminal part of its pro-hormone (NT-pro-BNP) made it possible to use the test even in emergency care settings. Here we review the literature with special focus on assessment of BNP and NT-pro-BNP in the following clinical settings: community screening for LV dysfunction, primary diagnosis of heart failure in general practice and emergency department (ED) and risk stratification in cardiac dysfunction and acute coronary syndromes. In addition, we discuss which applications can be recommended for daily clinical use from the cardiologist's point of view.

Topics: Coronary Disease; Genetic Markers; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments

Serum testing for the hormone B-type natriuretic peptide (BNP) may have clinical utility in congestive heart failure (CHF). This hormone is secreted predominantly by the left ventricular myocardium in patients with CHF. Measurement of serum BNP may improve diagnosis of CHF and may also help guide therapy in patients with CHF. The literature regarding the clinical utility of BNP measurement in CHF is reviewed.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity

The diagnosis of heart failure is difficult, with both overdiagnosis and underdiagnosis occurring commonly in practice. Natriuretic peptides have been proposed as a possible test for assisting diagnosis. We assessed the diagnostic accuracy of brain natriuretic peptide (BNP), including a comparison with atrial natriuretic peptide (ANP).. Electronic searches were conducted of MEDLINE and EMBASE from January 1994 to December 2002 and handsearches of reference lists of included studies. We included studies that assessed the diagnostic accuracy of BNP against echocardiographic or clinical criteria or that compared the diagnostic accuracy of BNP with ANP. Two reviewers assessed studies for inclusion and quality and extracted the relevant data. A meta-analysis was performed by pooling the diagnostic odds ratios for studies that used a common reference standard.. Twenty studies were included. For the 8 studies (n = 4086) that measured BNP against the criterion of left ventricular ejection fraction of 40% or less (or equivalent), the pooled diagnostic odds ratio was 11.6 (95% confidence interval, 8.4-16.1). The pooled diagnostic odds ratio was greater, 30.9 (95% confidence interval, 27.0-35.4), in the 7 studies (n = 2374) that measured BNP against clinical criteria (generally a consensus view using all other clinical information). The diagnostic odds ratio was similar in studies conducted in general practice and in hospital settings. Three studies compared BNP with N-terminal-ANP, a precursor form of ANP, and pooling of the results of these studies showed BNP to be a more accurate marker of heart failure than NT-ANP.. Brain natriuretic peptide is an accurate marker of heart failure. Use of a cutoff value of 15 pmol/L achieves high sensitivity, and BNP values below this exclude heart failure in patients in whom disease is suspected. As the diagnostic odds ratio for BNP is greater when assessed against clinical criteria than against left ejection fraction alone, BNP may also be detecting patients with "diastolic" heart failure.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Myocardium; Natriuretic Peptide, Brain

Plasma levels of various neurohumoral factors are activated and have an important role of the pathophysiology of congestive heart failure (CHF). Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are secreted from cardiomyocytes in response to atrial or ventricular wall stretch. The natriuretic peptides have a fundamental role in cardiovascular remodeling, volume homeostasis, and the response to myocardial injury. Clinical investigations of these peptides have focused on their diagnostic usefulness for heart failure and left ventricular dysfunction and their prognostic usefulness after acute coronary syndromes and heart failure. In patients with left ventricular systolic dysfunction, a high plasma BNP level is an independent prognostic predictor of CHF patients, suggesting 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. BNP is more useful than ANP for diagnosis and management of CHF. Recently, rapid BNP assay is available in our country, rapid measurement of BNP in the emergency department may improve the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment. In addition, BNP-guided treatment of heart failure may reduce total cardiovascular events, and delayed time to first event combination with intensive clinically guided treatment.

Topics: Biomarkers; Clinical Trials as Topic; Heart Failure; Humans; Mass Screening; Monitoring, Physiologic; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left

Heart failure is the leading cause of hospitalizations in the USA, and is associated with significant morbidity, mortality and resource utilization. Established therapies for chronic heart failure have been shown to improve outcomes, but treatment for decompensated heart failure remains largely empiric. Nesiritide (Natrecor) is a synthetic analog of human B-type natriuretic peptide, a peptide released by the ventricular myocardium in response to increased wall tension. The physiologic effects of human B-type natriuretic peptide include natriuresis, vasodilation and neurohormonal modulation. In clinical trials, nesiritide has been shown to decrease cardiac filling pressures, increase cardiac index, and improve the clinical status of patients with acute decompensated heart failure. Compared with other available intravenous agents for heart failure, nesiritide is effective, generally well-tolerated with few adverse effects, and does not require invasive monitoring during administration. Nesiritide has proven to be an effective new treatment for patients with decompensated heart failure.

Topics: Aged; Aged, 80 and over; Biological Availability; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Failure; Humans; Male; Maximum Tolerated Dose; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Survival Rate; Treatment Outcome

Topics: Acute Disease; Antibodies, Monoclonal; Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Immunoenzyme Techniques; Immunoradiometric Assay; Natriuretic Peptide, Brain; Severity of Illness Index

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

Topics: Biomarkers; Evidence-Based Medicine; Heart Failure; Humans; Infusions, Intravenous; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Stroke; Treatment Outcome

THREE PRINCIPLE REASONS:Confirming the existence of heart failure in an elderly patient is difficult because of the intricacy of the symptomatology with that of other diseases, the lesser willingness of the practitioner to diagnose it, and the limited access to explorations such as echocardiography. RELATIVELY UNSPECIFIC CLINICAL SIGNS:Dyspnoea, signs of low heart rate, peripheral oedema, crepitations or tachycardia are all inconstant signs or difficult to interpret. The response to a therapeutic test with diuretics is very useful. REGARDING SUPPLEMENTARY EXAMINATIONS: An echocardiography should be systematically performed in elderly patients in order to specify the type of heart failure and the extent of an eventually curable valvulopathy. Validation of the measurement of brain natriuretic peptide (BNP) in elderly patients is in progress.

Topics: Aged; Aging; Diagnosis, Differential; Dyspnea; Echocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain; Tachycardia

Within the last five years, assay systems for measurement of plasma levels of brain natriuretic peptide (BNP) have been approved as a diagnostic aid for heart failure (HF). Similarly, nesiritide, a recombinant form of human BNP, has been approved for the treatment of acutely decompensated HF. Both BNP as a diagnostic test and a therapeutic modality are rapidly becoming integrated into clinical practice. The purpose of this review is to provide a brief overview of the physiology of the natriuretic peptides relevant to their informed clinical use. The current literature regarding the utility of measuring BNP for the diagnosis and management of HF is reviewed and practical recommendations regarding the interpretation of BNP levels are offered. The clinical literature regarding the use of recombinant BNP for the treatment of HF is reviewed, underscoring current gaps in our knowledge regarding the indications for and benefits of this novel agent.

Topics: Atrial Natriuretic Factor; Cardiomegaly; Diuresis; Heart Failure; Humans; Kidney; Myocardial Infarction; Natriuresis; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; ROC Curve; Survival Analysis; Treatment Outcome; Vasodilation; Ventricular Remodeling

Topics: Animals; Diastole; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Systole

The authors give a brief summary about the process and significance of cardiotoxicity produced by chemotherapy and irradiation used for malignancy. After the introduction, those invasive and noninvasive processes are put into focus and explained in detail, which are applied in the research of the effects of cardiotoxic chemotherapy. The clinical importance of this research is the life prolongation effect of the treatment, which allows the late-appearing toxic cardiomyopathy, resulting in congestive heart failure and increasing mortality. Summarizing the last decade's progress in research, it is evident that even in the planning of chemotherapy, the cardiovascular risks have to be taken into account, because they can greatly influence the cardiac side effect of the treatment.

Topics: Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Diastole; Electrocardiography; Heart Failure; Heart Rate; Humans; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Radionuclide Ventriculography; Systole; Ventricular Function, Left

B-type natriuretic peptide (BNP) is a cardiac neurohormone released as preproBNP and then enzymatically cleaved to N-terminal-proBNP and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with heart failure. Currently, BNP assay is used as a diagnostic and prognostic aid in congestive heart failure. In general, a BNP level <100 pg/mL excludes acutely decompensated heart failure. This article sorts out the literature concerning the practical use of BNP in a variety of clinical scenarios.

Topics: Acute Disease; Adult; Age Factors; Aged; Algorithms; Ambulatory Care; Body Weight; Decision Trees; Drug Monitoring; Dyspnea; Female; Heart Failure; Humans; Male; Metabolic Clearance Rate; Middle Aged; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Sex Characteristics; Treatment Outcome

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

Nesiritide is a synthetic human B-type natriuretic factor that has a balanced arterial and venous dilator effect, with natriuretic, diuretic, anti-aldosterone and antisympathetic action. It was launched in the US for the treatment of acute decompensated heart failure (ADHF) in August 2001 and, recently, in Switzerland and Israel. It has been demonstrated to provide more rapid and sustained haemodynamic stabilisation than glyceryl trinitrate and significant symptomatic improvement vs. placebo at 3 h, and to be safer than dobutamine. The main side effects associated with nesiritide therapy are asymptomatic and symptomatic hypotension, which are treated with dose reduction. When compared to dobutamine, the increased acquisition costs of nesiritide are completely offset by reduced intensity of hospital admissions and reduced readmission rate at 3 weeks.

Topics: Acute Disease; Drug Costs; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Early diagnosis and treatment of acute decompensated heart failure (ADHF) results in improved clinical outcomes, reduced resource utilization, improved quality of life, and lower treatment costs. Currently, heart failure results in nearly 1 million hospitalizations annually in the United States, and 50% of hospitalized patients are readmitted within 6 months of initial discharge. The costs associated with resource utilization are substantial. Despite the personal and societal burden of this condition, until recently, very little progress had been made in optimizing treatment of ADHF. Nesiritide, a human recombinant B-type natriuretic peptide, is a safe, effective vasodilator that can be easily used early in the emergency department to improve outcomes in ADHF.

Topics: Cardiotonic Agents; Decision Trees; Emergency Treatment; Heart Failure; Humans; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Vasodilator Agents

Chronic decompensated heart failure (HF) is costly to manage because of frequent episodes of acute decompensation that result in hospitalization. Patients with chronic decompensated HF may have inadequate hemodynamic responses or limited tolerance of oral HF medications and therefore may require parenteral administration of vasoactive agents. Intermittent infusions of inotropic agents are no longer recommended, but preliminary data suggest that intermittent nesiritide may be a safe and effective adjunct to oral drug therapy for select patients at risk for further episodes of decompensation. In other patients, nonpharmacologic approaches used in combination with drug therapy may help improve functional status and reduce mortality.

Topics: Ambulatory Care; Clinical Trials as Topic; Decision Trees; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Heart failure is a major public health problem and despite significant advances in treatment remains the only cardiovascular disease still on the rise. Because this patient population often has a number of other concomitant diseases, including hypertension, coronary artery disease, arrhythmias, diabetes, chronic obstructive pulmonary disease, and renal insufficiency, diagnosis can be difficult. Currently, diagnosis of acute decompensated heart failure (ADHF) relies largely on patient history, signs, and symptoms. Rapid and accurate diagnosis of ADHF in the emergency department (ED) is essential for timely initiation of treatment. Thus, any means for improving the speed and accuracy of ADHF diagnosis in the ED can contribute to better clinical and economic outcomes. Measurement of circulating endogenous B-type natriuretic peptide (BNP) has proven to be a sensitive and specific test for heart failure that can easily be used in the ED. Used in conjunction with standard diagnostic procedures, measurement of BNP levels can improve the accuracy of ADHF diagnosis during the critical window for optimal care.

Topics: Decision Trees; Diagnostic Techniques, Cardiovascular; Emergency Treatment; Heart Failure; Humans; Natriuretic Peptide, Brain

Topics: Biomarkers; Echocardiography; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Perioperative Care

B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzymatically cleaved to the N-terminal-proBNP and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with heart failure (HF). The BNP assay is currently used in diagnosis, prognosis, screening, and response to treatment for patients with HF. In general, a BNP level below 100 pg/mL excludes acutely decompensated HF and levels > 500 pg/ml indicate decompensation. There are supportive data for using BNP to guide both inpatient and outpatient HF diagnosis and treatment. When BNP is elevated in acute coronary syndromes, pulmonary embolism, and sepsis, it implies that subclinical left ventricular dysfunction is present and a higher mortality rate can be expected. Elevated BNP levels before cardiac surgery are associated with higher rates of atrial fibrillation and death. After bypass surgery, as left ventricular function improves, the BNP level can be expected to fall. Lastly, in patients with aortic stenosis, aortic regurgitation, and mitral regurgitation, BNP elevates and is associated or may precede the development of symptoms and possibly can serve as a trigger for additional evaluation or intervention.

Topics: Algorithms; Cardiovascular Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis

The use of human B-type natriuretic peptide (BNP, nesiritide) as a therapeutic intervention is now well established for patients with acute decompensated heart failure. Nesiritide mimics the actions of endogenous BNP by binding to and stimulating receptors in the heart, kidney, and vasculature. Postsurgical patients are typically managed with various combinations of vasodilators, diuretics, and inotropes. Many of these therapeutic interventions lack significant proof of efficacy and are potentially deleterious to these patients, despite the acute hemodynamic improvement that results from their use. Use of nesiritide may supplant some of these therapies as an equally efficacious and possibly safer alternative in patients with decompensated heart failure. Nesiritide is a unique, balanced vasodilator that markedly decreases the signs and symptoms of heart failure in perioperative patients, and also may decrease the need for inotropic agents. This review summarizes nesiritide's mechanism of action and addresses special concerns and practical considerations for cardiothoracic surgeons and anesthesiologists. Overall, nesiritide appears to be an effective and safe therapeutic option in perioperative patients with decompensated heart failure.

Topics: Acute Disease; Cardiopulmonary Bypass; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

The natriuretic peptides BNP and NT-proBNP are synthesized and released dependent of wall tension in the atria and ventricles. The determination of these peptides in a rapid test makes two markers available that closely correlate with the severity of heart failure. Systolic as well as diastolic left ventricular dysfunction are recorded, but a clear differentiation cannot be made by marker determination. Particularly important is the high negative predictive value and the certainty with which heart failure can be excluded when the plasma level is normal. Besides the diagnostic assistance, natriuretic peptides have a high and above all independent value to assess the prognosis of heart failure, acute coronary syndromes and partially of atrial fibrillation. It is possibile to optimize the therapy of heart failure according to the plasma level.

Topics: Acute Disease; Antihypertensive Agents; Biomarkers; Carbazoles; Carvedilol; Clinical Trials as Topic; Diagnosis, Differential; Dyspnea; Echocardiography; Family Practice; Heart Failure; Humans; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Prognosis; Propanolamines; Sensitivity and Specificity; Vasodilator Agents

B-type natriuretic peptide (BNP) is a cardiac neurohormone and is released as prepro BNP and then enzymatically cleaved to the N-terminal proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP have been used to identify patients with heart failure (HF). Clinical considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, interpretation of their units of measure, and the rapid availability of the test results. The BNP assay is currently used as a diagnostic and prognostic aid in HF. In general, a BNP level below 100 pg/mL excludes acutely decompensated HF. Recombinant, human BNP (nesiritide) is an approved intravenous treatment for acute, decompensated HF. This paper reviews the literature concerning the use of this peptide as a diagnostic test and as an intravenous therapy.

Topics: Adult; Aged; Biomarkers; Female; Heart Failure; Heart Function Tests; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Nerve Tissue Proteins; Prognosis; Protein Precursors; Randomized Controlled Trials as Topic; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Survival Rate; Treatment Outcome

Nesiritide (Natrecor) is a recombinant form of human B-type (brain) natriuretic peptide that has beneficial vasodilatory, natriuretic, diuretic and neurohormonal effects. The drug is administered intravenously for the management of patients with decompensated congestive heart failure (CHF). In the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study, patients hospitalised with acute decompensated CHF who received nesiritide had significantly greater mean reductions from baseline in pulmonary capillary wedge pressure 3 hours after starting treatment than nitroglycerin or placebo recipients (-5.8 vs -3.8 and -2 mm Hg, respectively); all patients also received standard therapy (e.g. intravenous diuretics). Improvements in other haemodynamic parameters were also seen in nesiritide recipients. In addition, significantly more nesiritide than placebo recipients reported an improvement in dyspnoea after 3 hours' treatment in VMAC, whereas there was no significant difference between nitroglycerin and placebo recipients. Improvements in global clinical status, dyspnoea and fatigue were also seen with nesiritide in another active-comparator study and in a placebo-controlled study. In VMAC, there was no significant difference between nesiritide and nitroglycerin recipients in 6-month mortality. In the other active-comparator trial, 6-month mortality was significantly lower in recipients of nesiritide 0.015 micro g/kg/min than in dobutamine recipients (although mortality was not a prespecified endpoint and this result should be interpreted with caution). In this same study, the 21-day all-cause hospital readmission rate was significantly lower with nesiritide 0.015 micro g/kg/min than with dobutamine and the duration of active drug treatment was significantly shorter with nesiritide than with dobutamine. Nesiritide is generally well tolerated. In VMAC, significantly more adverse events occurred with nitroglycerin than with nesiritide. The most common adverse events reported during the first 24 hours of therapy in nesiritide and nitroglycerin recipients included general pain, abdominal pain, catheter-related pain, headache, nausea, asymptomatic and symptomatic hypotension, nonsustained ventricular tachycardia and angina pectoris. Most episodes of symptomatic hypotension resolved spontaneously or after an intravenous volume challenge of

Topics: Acute Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Natriuretic Agents; Natriuretic Peptide, Brain; Vasodilator Agents

To review preclinical and clinical information related to nesiritide, a recombinant form of B-type natriuretic peptide approved for treatment of acutely decompensated heart failure.. Primary and review articles were identified by MEDLINE search (1966-May 2002) using the key words natriuretic peptide and heart failure, and through secondary sources. Natrecor's document submitted for the Food and Drug Administration (FDA) New Drug Application were obtained from the FDA Web site.. Peer-reviewed articles and abstracts of randomized clinical trials in humans were included in this review.. Nesiritide has beneficial actions for treatment of heart failure, including arterial and venous dilatation, enhanced sodium and urinary excretion, and suppression of the renin-angiotensin-aldosterone and sympathetic nervous systems. It has been shown to improve hemodynamic parameters, primarily pulmonary capillary wedge pressure, as well as clinical symptoms in patients with acutely decompensated heart failure. Nesiritide produced more rapid hemodynamic improvement and caused significantly fewer adverse effects than intravenous nitroglycerin. The incidence of hypotension, the most common adverse effect, was comparable between nesiritide and nitroglycerin. Additionally, nesiritide is associated with a lower incidence of arrhythmias than dobutamine and has a neutral effect on mortality.. Nesiritide offers an alternative for management of acutely decompensated heart failure. It is considered an option for patients who do not respond to other vasodilators, inotropes, or diuretics and for those at high risk of arrhythmias. Further pharmacoeconomic investigations for nesiritide are warranted.

Topics: Half-Life; Heart Failure; Hemodynamics; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Aged; Diuretics; Dobutamine; Enalaprilat; Female; Heart Failure; Hemodynamics; Hospitalization; Humans; Hydrazones; Injections, Intravenous; Male; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroprusside; Pulmonary Wedge Pressure; Pyridazines; Renal Agents; Simendan; Vasodilator Agents

Topics: Acute Disease; Drug Approval; Dyspnea; Forecasting; Heart Failure; Hospitalization; Humans; Hydrazones; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Pyridines; Randomized Controlled Trials as Topic; Severity of Illness Index; Simendan; Tetrazoles; Treatment Outcome; Vasodilator Agents

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiotonic Agents; Diuretics; Dobutamine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Randomized Controlled Trials as Topic; Receptors, Atrial Natriuretic Factor; Vasodilator Agents

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

As briefly summarized in this report, the prevalence of heart failure is high and it will continue to rise as the population ages. There will be over 1 million hospitalizations for acutely decompensated heart failure this year. The goals of treatment for patients with acutely decompensated heart failure are to lower cardiac filling pressures, remove fluids and improve symptoms of dyspnea, decrease vascular resistance, and increase cardiac output without activating the RAAS. There are few guidelines for the treatment of individuals with acutely decompensated heart failure and many different agents have been used in patients with this disease. Many of these drugs are not completely effective and may lead to serious adverse events. BNP is a natural protein produced by myocardial cells in response to ventricular distension, and its level is dramatically increased in patients with heart failure. The results of several recent clinical trials have shown that administration of nesiritide is safe and highly effective for the initial treatment of patients with acutely decompensated heart failure and can help physicians and nurses meet treatment goals for the management of patients with this serious condition.

Topics: Acute Disease; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

More than 4.5 million Americans have congestive heart failure (CHF), close to 550,000 new cases are diagnosed each year, and one third of known patients with CHF are annually admitted to the hospital. Emergency department diagnosis of CHF is often based on history and physical examination findings along with results of ancillary tests, such as chest radiography and ECG. Although signs and symptoms of fluid overload, such as lower extremity edema and dyspnea, raise the suspicion of CHF, their lack of sensitivity makes them poor screening tools. The natriuretic peptides are promising markers of myocardial dysfunction and heart failure. Because of their relationship to myocardial pressure and stretching, natriuretic peptides have been investigated over the past 5 decades as both diagnostic and prognostic markers in acute coronary syndromes and CHF. This article discusses each of the natriuretic peptides and attempts to delineate their potential diagnostic and prognostic roles in the ED.

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Discriminant Analysis; Dyspnea; Emergency Treatment; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Patient Admission; Peptide Fragments; Prognosis; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Stroke Volume; United States

Evidence suggests that adrenomedullin (AM) plays a role in the pathophysiology of heart failure. Circulating concentrations of AM are elevated in cardiovascular disease in proportion to the severity of cardiac and hemodynamic impairment. Raised plasma AM levels following acute cardiac injury and in heart failure provide prognostic information on adverse outcomes. In heart failure, elevated circulating AM also identifies patients likely to receive long-term benefit from inclusion of additional anti-failure therapy (carvedilol). Administration of AM in experimental and human heart failure induces reductions in arterial pressure and cardiac filling pressures, and improves cardiac output, in association with inhibition of plasma aldosterone (despite increased renin release) and sustained (or augmented) renal glomerular filtration and sodium excretion. Furthermore, AM in combination with other therapies (angiotensin-converting enzyme inhibition and augmentation of the natriuretic peptides) results in hemodynamic and renal benefits greater than those achieved by the agents separately. Manipulation of the AM system holds promise as a therapeutic strategy in cardiac disease.

Topics: Adrenomedullin; Amino Acid Sequence; Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Heart Failure; Humans; Molecular Sequence Data; Natriuretic Peptide, Brain; Peptides; Sequence Alignment; Sheep

Human BNP serves to compensate for deteriorating cardiac function causing preload and afterload reductions, natriuresis, diuresis, suppression of the renin-angiotensin-aldosterone system (RAAS) and endothelin-1, and lowering of norepinephrine. Based on its unique pharmacologic profile, nesiritide results in clinically significant balanced vasodilation of arteries and veins, and may be well suited for patients presenting with various scenarios of decompensated CHF usually due to volume overload (NYHA classes II-IV). More than 1000 subjects have participated in clinical trials with nesiritide and more than 55,000 patients have been treated with nesiritide since it was approved for use in August 2001. Unlike nitroglycerin, tachyphylaxis did not appear to occur with Natrecor. The complete efficacy profile of nesiritide included preload reduction (PCWP and RAP), reductions in pulmonary artery pressures, afterload reduction (systemic vascular resistance), and increases in cardiac index and stroke volume index (which are dose-dependent and not the result of a direct inotropic effect), without increasing heart rate. Unlike inotropes, the beneficial hemodynamic effects produced by nesiritide do not cause an increase in myocardial oxygen consumption (MVO(2)), an important consideration for patients with acutely decompensated heart failure. Because Nesiritide is not an inotrope, it does not affect myocardial contractility, as does a beta-adrenergic receptor agonist, or a phosphodiesterase III inhibitor. As a result, nesiritide is not arrhythmogenic. Nesiritide should be considered for patients presenting with acutely typical or useful decompensated heart failure, especially those with dyspnea at rest or with minimal activity.

Topics: Clinical Trials as Topic; Heart Failure; Humans; Injections, Intravenous; Natriuretic Agents; Natriuretic Peptide, Brain

Topics: Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Plasma concentration of brain natriuretic peptide (BNP), as measured by the Triage BNP Test, is approved by the Food and Drug Administration to aid in the diagnosis of heart failure. This diagnostic test is available in many institutions. The purpose of this article is to help the physician know the appropriate time to order this test and to aid in interpreting results. To achieve this goal, we review the physiology of BNP, clinical studies that support its use for diagnosing heart failure, and confounding variables to consider when BNP is being used clinically. We show that the BNP test can be extremely helpful when used in the correct clinical setting.

Topics: Biomarkers; Confounding Factors, Epidemiologic; Heart Failure; Humans; Natriuretic Peptide, Brain

Diuretics continue to be a mainstay in patients with CHF. Conventional diuretic therapy is associated, however, with potentially deleterious neurohumoral activation and renal impairment. It is not known to what extent these neurohumoral effects are offset by concurrent therapy with ACE-I, beta-blockers, and other agents. In the past, there was no alternative to conventional diuretic therapy, so their potential for adverse outcome in the long term could not be assessed. Enhancement of the natriuretic peptide system could provide us with a better strategy to treat sodium and water retention. In a unique way, the natriuretic peptides combine several of the beneficial actions of the other diuretics, but without the associated cost. Natriuretic peptides, like conventional diuretics, are natriuretic and diuretic. There are important differences, however. First, unlike conventional diuretics, NPs do not activate RAAS. Activation of this system is associated with progression of CHF. Second, NPs inhibit the sympathetic nervous system, the activation of which is associated with heart failure progression, myocyte necrosis and apoptosis, and arrhythmias. Third, unlike conventional diuretics that lead to a decrease in GFR by reflex mechanisms. NPs maintain or even improve GFR. We now appreciate that some "old" drugs may be beneficial to CHF patients in a new way, as is the case with spironolactone. The survival benefit of this aldosterone antagonist is clear: its usefulness, however, may be more a result of both its antifibrotic actions in addition to its tradional role as a potassium-sparing and natriuretic agent. It is hoped that the SARAs will provide the same survival benefit, but with fewer of the sex-steroid side effects. In addition, AVP-receptor antagonists may become useful tools in the treatment of patients with hyponatremia. Likewise, the A1 AR antagonists may find a role in the CHF armamentarium by providing good diuresis and natriuresis while at the same time maintaining GFR through inhibition of TGF. Many questions remain unanswered, and studies are needed to demonstrate that the positive results seen in basic research translate into improved morbidity and mortality.

Topics: Aldosterone; Antidiuretic Hormone Receptor Antagonists; Atrial Natriuretic Factor; Diuresis; Diuretics; Heart Failure; Humans; Kidney; Mineralocorticoid Receptor Antagonists; Natriuresis; Natriuretic Peptide, Brain; Neprilysin; Purinergic P1 Receptor Antagonists; Sodium Chloride; Water-Electrolyte Imbalance

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Canada; Cardiology; Defibrillators, Implantable; Heart Failure; Humans; Natriuretic Peptide, Brain; Societies, Medical

Since the discovery of atrial natriuretic peptide, the unravelling of the natriuretic peptide system has been a story of scientific success. However, bridging the gap between bench and bedside has proved difficult, and as yet has not provided any major clinical progress. In this review we will first give a detailed outline of the key elements constituting the natriuretic peptide system. Secondly, we will briefly explain the underlying rationale, basic concepts and evidence behind currently pursued strategies to potentiate the natriuretic peptide system. Thirdly, we will highlight some of the problems that have so far hindered successful translation of these theoretically viable treatment options into tangible clinical progress.

Topics: Animals; Atrial Natriuretic Factor; Cardiotonic Agents; Heart Failure; Humans; Mice; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptide Hormones

Topics: Atrial Natriuretic Factor; Biomarkers; Clinical Trials as Topic; Diagnosis, Differential; Heart Failure; Heart Rate; Hemodynamics; Humans; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Stroke Volume; Troponin T

Neurohumoral factors, which is divided to two groups, are activated in patients with congestive heart failure(CHF). One is cardiotoxic biochemical markers such as nor-epinephrine, angiotensin II, endothelin-1, and vasopressin, the other is cardioprotective biochemical markers such as atrial natriuretic peptide, and brain natriuretic peptide (BNP). Among various neurohumoral factors, plasma level of BNP is the most useful marker to diagnose and evaluate the severity and prognosis of CHF patients. The reason why the usefulness of plasma BNP is 1) BNP is of ventricular origin, 2) BNP reflects hemodynamic abnormalities(high left ventricular end-diastolic pressure and/or low left ventricular ejection fraction), 3) Attenuation of biological compensation of beneficial effects of BNP(vasodilation, diuresis) in advanced-staged CHF.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Pressure

B-type natriuretic peptide (BNP), a neurohormone synthesized in the cardiac ventricles, is released as preproBNP and then enzymatically cleaved to the N-terminal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP 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. The BNP assay currently available in North American markets, approved for use as a diagnostic aid in CHF and a prognostic marker in acute coronary syndromes (ACS), has particular advantages because it is available at the point of care and has had considerable use in clinical studies. In general, a BNP level less than 100 pg/mL has strong negative predictive value for CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated CHF. BNP has been shown to be a reliable and independent predictor of sudden cardiac death. In the absence of renal dysfunction, NT-proBNP has also been shown to be of diagnostic value in CHF, related to CHF severity, predictive of sudden death, and prognostic for death in ACS. This article reviews the literature concerning the use of these peptides in a variety of clinical scenarios.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Severity of Illness Index

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

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles. It is released as N-terminal pro-BNP (NT-proBNP) and cleaved enzymatically to the NT fragment and the immunoreactive BNP. Measurement of BNP is now available as a rapid bedside assay that is easily available to physicians in an office, clinic, emergency department, or inpatient setting. It has proven utility in the emergency department diagnosis of congestive heart failure (CHF) in patients with unclear causes of dyspnea. The use of BNP level as a criterion for hospital admission has been studied as has its use as an aid in decision-making regarding the adequacy of treatment and readiness for hospital discharge. Treatment of chronic CHF in outpatients using BNP as a guide for the intensity of pharmacological therapy shows promise in further decreasing the rate of adverse events associated with this diagnosis. Other uses for BNP measurement include the prognostication of CHF exacerbation and myocardial infarction, and screening those at risk to identify patients that may benefit from early intervention and treatment of early CHF.

Topics: Atrial Natriuretic Factor; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Outpatients; Prognosis; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Decision Making; Heart Failure; Hemodynamics; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Treatment Outcome; Vasodilator Agents

The role of the clinical laboratory in emergency cardiac medicine is rapidly evolving; with recent redefinitions of acute myocardial infarction (AMI) and unstable angina (UA) based on troponin levels, recommended acceleration of cardiac testing protocols, and increased clinical measurement of B-type natriuretic peptide (BNP). We briefly review the background pathophysiology of acute coronary syndromes (ACS) and congestive heart failure (CHF), along with an overview of the biochemistry and physiology of the natriuretic peptides.. The assay principles and performance characteristics of the rapid BNP assays are discussed. The performance characteristics of troponin assays are at the center of controversy regarding the redefinition of AMI and UA, and will be discussed.. We review the rapidly expanding evidence regarding the clinical utility of BNP for CHF patients. While BNP has gained wide acceptance as a rapid diagnostic tool, considerable controversy remains concerning its potential for prognosis, screening, and therapeutic monitoring. Although a thorough discussion of the use of cardiac markers is well beyond the scope of this review, overviews of the redefinitions of AMI and UA, and the trend toward accelerated testing protocols to obtain a quicker diagnosis or ruling-out of AMI are included. In addition to accelerating the retesting of existing markers, a recent test for ischemia modified albumin (IMA) promises another quantum leap in cardiac diagnoses.. The positive impact of these developments on the healthcare costs and overall improvement in the quality of healthcare delivery will be discussed. A brief analysis of the downstream costs of BNP testing is also offered.

Topics: Atrial Natriuretic Factor; Biomarkers; Emergencies; Heart Failure; Humans; Medical Laboratory Science; Myocardial Ischemia; Natriuretic Peptide, Brain

In 2002, several studies were directed at new developments in the management of heart failure. In the COPERNICUS study, the previously reported benefits of the beta-adrenoreceptor blocker carvedilol regarding morbidity and mortality in patients with mild-to-moderate heart failure were also found in patients with severe heart failure. Carvedilol not only improves survival but when given in addition to conventional therapy, ameliorates the severity of heart failure and reduces the risk of clinical deterioration, hospitalisation and other serious adverse events. The diagnostic value of B-type natriuretic peptide (BNP) in patients with congestive heart failure has been a topic of study for the past five years. Many questions still need to be answered but the results of a study by Maisel et al. show that BNP is not only of diagnostic value but is also important for prognosis and evaluation of therapy. A substudy of the Val-HeFT study focussed on the effects of the angiotensin receptor blocker valsartan on BPN and noradrenaline levels. Valsartan significantly reduced the combined endpoint of mortality and morbidity and improved clinical signs and symptoms in patients with heart failure, if added to prescribed therapy. However, in a post-hoc observation an adverse effect on mortality and morbidity was seen in the subgroup receiving valsartan, an ACE inhibitor and a beta-blocker, which raised concern about the potential safety of this specific combination. And finally, interesting work by Abraham et al. on cardiac resynchronisation through atrial-synchronised biventricular pacing clearly shows that this therapy can produce a significant clinical improvement in patients with moderate-to-severe congestive heart failure and intraventricular conduction delay.

Topics: Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiovascular Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Survival Analysis

Topics: Angiotensin-Converting Enzyme Inhibitors; Aquaporin 2; Aquaporin 6; Aquaporins; Heart Failure; Humans; Kidney; Kidney Diseases; Natriuretic Peptide, Brain; Vasopressins

Nesiritide is an effective agent for the treatment of decompensated CHF. However, the VMAC trial shows that the agent's efficacy and safety are actually more similar than dissimilar to those of nitroglycerin. Indeed, objective reviews have placed nesiritide as a second-line agent behind current standard drug therapy. Finally, nesiritide is approximately 40 times the purchase price of standard agents such as nitroglycerin. For these reasons, we feel that nesiritide should not be considered as first-line therapy. Reflecting this notion, one institution has implemented a protocol that recommends administration of nitroglycerin and intravenous diuretics (using > or = 2 times the usual daily diuretic dose) before using nesiritide. In light of the existing data, we feel that this approach appears to be an appropriate and prudent one for nesiritide's place in therapy.

Topics: Acute Disease; Health Care Costs; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitroglycerin; Survival Rate; Treatment Outcome

Abstract B-natriuretic peptide (BNP) is a 32-amino acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. BNP levels are elevated in patients with symptomatic left ventricular dysfunction, and levels correlate with severity of symptoms and with prognosis. Numerous studies indicate that BNP may considerably improve the management of patients with heart failure and may become a routine serum parameter in clinical medicine. In this review, the utility of BNP in different clinical settings will be discussed.

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Diagnosis, Differential; Dyspnea; Emergencies; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Reference Values; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Ventricular Dysfunction, Left

Pooled data from trials comparing nesiritide with dobutamine for treatment of acute decompensated congestive heart failure were combined with national hospital cost data in an economic model. Results indicate that the acquisition cost of nesiritide is fully offset by decreased hospital costs.

Topics: Acute Disease; Age Distribution; Aged; Cardiotonic Agents; Dobutamine; Drug Costs; Female; Heart Failure; Hospital Costs; Humans; Life Expectancy; Male; Middle Aged; Models, Econometric; Monte Carlo Method; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Admission; Predictive Value of Tests; Sex Distribution; Survival Analysis; Treatment Outcome; United States; Value of Life

The benefits of nesiritide for the treatment of acute decompensated heart failure (ADHF) are discussed. In order to understand the goals of ADHF therapy, it is important to recognize the complex interplay between hemodynamic and neurohormonal abnormalities in patients suffering from heart failure. Goals of therapy include improvement in hemodynamic parameters, relief of symptoms, and minimization of adverse effects. Until recently, therapy with diuretics, positive inotropes, and intravenous vasodilators was the standard of care for treating ADHF. Nesiritide is the newest agent available for treating ADHF and may offer several benefits over standard of care therapy. It is important to remember that therapy for ADHF should not replace chronic oral heart failure therapy, nor should focus on prevention of ADHF episodes be lost.

Topics: Acute Disease; Cardiotonic Agents; Clinical Trials as Topic; Diuretics; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Vasodilator Agents

Topics: Clinical Trials as Topic; Economics, Hospital; Emergency Medical Services; Heart Failure; Hospitals; Humans; Length of Stay; Natriuretic Peptide, Brain; Patient Readmission; Vasodilator Agents

Many claims have been made in recent years regarding the utility of plasma B-type natriuretic peptide (BNP) concentration measurements in the diagnosis, risk stratification and monitoring of patients with heart failure. This paper summarizes the current evidence and provides guidance for practising clinicians. Overall, plasma BNP testing appears to be of most value in the diagnostic arena, where it is likely to improve the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test for suspected cases of new heart failure in breathless patients presenting to either the outpatient or emergency care settings; it is not a replacement for echocardiography and full cardiological assessment, which will be required for patients with an elevated BNP concentration. Although work is ongoing in establishing the 'normal' values of BNP, heart failure appears to be highly unlikely below a plasma concentration of 100 pg/ml. However, as BNP levels rise with age and are affected by gender, comorbidity and drug therapy, the plasma BNP measurement should not be used in isolation from the clinical context.

Topics: Ambulatory Care; Clinical Laboratory Techniques; Emergency Service, Hospital; Fluorescent Antibody Technique; Heart Failure; Humans; Luminescent Measurements; Natriuretic Peptide, Brain; Point-of-Care Systems; Prognosis; Sensitivity and Specificity; Ventricular Dysfunction, Left

Congestive heart failure (CHF) is a leading cause of adult hospitalization in the United States, and despite advancements in treatment, the disease remains a major clinical challenge. The chief symptom of CHF is dyspnea, but in the urgent-care setting, it is often difficult to distinguish between cardiac and pulmonary causes of this symptom. B-type natriuretic peptide (BNP) is mainly synthesized, stored, and released in the ventricular myocardium and is strongly induced during ventricular-wall tension or stretch. It can be measured rapidly at the point of care and can be used to differentiate cardiac from pulmonary etiologies of dyspnea. In addition to its diagnostic utility, it also has prognostic value and may help guide the treatment of patients with CHF. Thus, it is likely that future algorithms incorporating BNP levels and other clinical indicators will become available to guide critical-care physicians in making management decisions for their CHF patients.

Topics: Biomarkers; Dyspnea; Heart Failure; Heart Ventricles; Humans; Myocardium; Natriuretic Peptide, Brain; United States

B-type natriuretic peptide (BNP) is a cardiac neurohormone released as pre-proBNP and then enzymatically cleaved to the N-terminal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP have been used to identify patients with heart failure (HF). Clinical considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, interpretation of their units of measure, and the rapid availability of the test results. The BNP assay is currently used as a diagnostic and prognostic aid in HF and as a prognostic marker in acute coronary syndromes (ACS). In general, a BNP level less than 100 pg/mL excludes acutely decompensated HF. In the absence of renal dysfunction, NT-proBNP has also been shown to be of diagnostic value in HF, related to HF severity, predictive of sudden death, and prognostic for death in ACS. This article will sort out the literature concerning the use of these peptides in a variety of clinical scenarios.

Topics: Biomarkers; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prevalence; Prognosis; Risk Factors; Severity of Illness Index

Despite significant advances in medical therapy, patients with heart failure remain at increased risk of overall mortality, progressive ventricular dysfunction, and sudden cardiac death. Although a number of individual clinical and laboratory variables have been identified as being associated with increased mortality risk in heart failure, there remains a clear need for an integrated, accurate method of determining prognosis. Elevated plasma B-type natriuretic peptide (BNP) has been demonstrated to be a powerful marker for prognosis and risk stratification in the setting of heart failure. Patients with elevated BNP levels have been shown to be at significantly higher risk for heart failure admission or death, and higher BNP levels are associated with progressively worse prognosis. Although cardiac troponins are a well-established diagnostic and prognostic marker in acute coronary syndromes, emerging data suggest that cardiac troponins also provide independent prognostic information in heart failure. Detection of cardiac troponins in the serum of patients with heart failure has been shown to be associated with an impaired hemodynamic profile, progressive decline in left ventricular systolic function, and shortened survival. Combining a marker of myocyte injury-cardiac troponin-with BNP in a multimarker strategy appears to be a useful tool for improving risk assessment and triage in patients with heart failure. Heart failure patients with detectable cardiac troponin I and high BNP levels have been shown to have a 12-fold increased mortality risk compared with those with both undetectable cardiac troponin I and lower BNP. Integrating this multimarker approach into the routine assessment of heart failure patients will allow clinicians to more accurately identify high-risk patients who may derive increased benefit from intensive management strategies.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Necrosis; Prevalence; Prognosis; Troponin; United States; Ventricular Dysfunction, Left

An understanding of the dynamic relationship between the coronary artery and left ventricular (LV) function is important in diagnosing and treating acute coronary disease. Measurement of B-type natriuretic peptide (BNP) provides rapid and accurate identification of patients with impaired LV function, which has proven valuable in differentiating between congestive heart failure (CHF) and symptoms attributable to pulmonary etiologies. Coronary artery and ventricular pathophysiology both are characterized by injury, functional aberrations, and subsequent remodeling. Ischemia occurs in both and accounts for virtually all significant adverse outcomes. The difference in BNP elevations seen in acute ischemia compared with those observed in chronic CHF is striking: Although even small BNP elevations in acute coronary syndromes have powerful prognostic value, it is not likely that they can be effectively used as a diagnostic marker for ischemia.

Topics: Acute Disease; Coronary Disease; Heart Failure; Humans; Natriuretic Peptide, Brain; Neurotransmitter Agents; Stroke Volume; Syndrome; United States; Ventricular Dysfunction, Left; Ventricular Function, Left

In the emergency setting, acute chest pain and shortness of breath represent common patient presentations. Cardiac biomarkers including myoglobin, creatine kinase (CK)-MB, troponin, and b-type natriuretic peptide provide diagnostic and prognostic information for patients with chest pain and shortness of breath. This article reviews the use of cardiac biomarkers in the emergency department to evaluate acute coronary syndrome and congestive heart failure.

Topics: Acute Disease; Biomarkers; Chest Pain; Coronary Disease; Creatine Kinase; Creatine Kinase, MB Form; Emergency Medical Services; Heart Failure; Humans; Isoenzymes; Natriuretic Peptide, Brain; Syndrome; Troponin; United States

The discovery of cardiac natriuretic peptides two decades ago has lead to considerable research to investigate their biochemical and physiological properties. Clearly the heart is not just a pump but is also an endocrine organ that together with the kidneys control volume overload. The natriuretic peptides are a group of structurally similar but genetically distinct peptides that exhibit diverse actions in cardiovascular, renal, and endocrine homeostasis. Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are of myocardial cell origin. BNP is released mainly from the left ventricle in response to volume overload and has become the first biochemical marker for the identification of individuals with congestive heart failure (CHF). The development of assays, including rapid point-of-care tests, has made BNP measurement a clinical reality.

Topics: Atrial Natriuretic Factor; Biological Assay; Biomarkers; Brain; Cardiac Volume; Heart Failure; Homeostasis; Humans; Immunoassay; Myocardium; Natriuretic Peptide, Brain

The therapeutic goals for patients hospitalized with acutely decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and to initiate heart failure therapies which will decrease disease progression and improve long-term survival. Nesiritide (recombinant B-type natriuretic peptide) is the first in a new class of therapeutic agents for the treatment of heart failure and has been demonstrated to offer a unique combination of safety and efficacy. The use of nesiritide on top of standard care including diuretic therapy, has been proven to lead to meaningful clinical benefits in a broad range of acutely decompensated heart failure patients. Nesiritide is an attractive therapeutic option because of its more rapid and sustained hemodynamic profile, more favorable effects on neurohormonal suppression, with less adverse effects than alternative intravenous heart failure treatments such as nitroglycerine, nitroprusside, dobutamine, or milrinone. The use of nesiritide is the most effective initial treatment approach among currently available strategies to reverse acutely decompensated heart failure and to facilitate optimization of the heart failure medical regimen.

Topics: Acute Disease; Disease Progression; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Vasodilation

For the acutely ill patient presenting to the emergency department with dyspnea, an incorrect diagnosis could place the patient at risk for both morbidity and mortality. The stimulus for BNP release is a change in left-ventricular wall stretch and volume overload. A rapid whole blood BNP assay has recently approved by the FDA (Triage BNP Test, Biosite Inc, San Diego CA) that allows one to quickly evaluate the dyspneic patient, and set the stage for the recently completed multinational Breathing Not Properly (BNP) study. The Breathing Not Properly Multinational Study was a seven center, prospective study of 1586 patients who presented to the emergency department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. BNP was accurate in making the diagnosis of CHF and correlated to severity of disease. It could have reduced clinical indecision by 74%. Algorithms are being developed for use in the emergency room which takes into account other illnesses that might raise BNP levels. BNP levels should be extremely important in ruling out and diagnosing decompensated CHF, as long as baseline "euvolemic" BNP values are known. Finally, it is possible that use of BNP levels might not only be helpful in assessing whether or not a dyspneic patient has heart failure, but it my turn out to be useful in making both triage and management decisions.

Topics: Acute Disease; Algorithms; Biological Assay; Biomarkers; Diagnosis, Differential; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Sensitivity and Specificity

The Emergency Department (ED) is a common location for acutely decompensated Heart Failure (HF) patients to seek care. Consequently, there is the opportunity for significant clinical benefits when care is managed appropriately. This article reviews the importance of an accurate diagnosis, the necessity to search for underlying precipitants of the HF decompensation, and the impact of early treatment on the subsequent length of hospitalization. It also discusses the value of the ED observation unit for short intensive management of HF, the potential financial benefits of this strategy, and the ability of nesiritide to decrease future revisits when used in this environment.

Topics: Acute Disease; Ambulatory Care; Emergency Service, Hospital; Heart Failure; Humans; Length of Stay; Natriuretic Peptide, Brain; United States

Topics: Heart Failure; Hospitalization; Humans; Monitoring, Physiologic; Natriuretic Peptide, Brain; Prognosis

With the increasing prevalence of heart failure, the greater spectrum of proven therapies, the broader spectrum of cardiac dysfunction qualifying for treatment and the recognition that heart failure is difficult to diagnose, the need for an indicator of both the diagnosis and the efficacy of treatment in this condition is clear. Plasma concentrations of the B-type natriuretic peptides are related to cardiac function and cardiovascular prognosis. They parallel hemodynamic indicators of cardiac dysfunction and may therefore act as indicators of the adequacy of therapy. In the one published trial of outpatient treatment of heart failure guided by plasma BNP, 69 patients (LVEF < 40%, NYHA II-IV) were randomised to treatment according to plasma peptide levels or a clinical score. The primary end point of total cardiovascular events was reduced in BNP-guided patients (19 versus 54 events) with p < 0.001 in a multivariate analysis. The natriuretic peptides and particularly plasma BNP and aminoterminal proBNP promised to provide an objective guide for optimising treatment in heart failure.

Topics: Ambulatory Care; Cardiotonic Agents; Forecasting; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; New Zealand; Outpatients; Prognosis

While measurement of plasma BNP concentration has been shown to be useful in the diagnosis of heart failure, its role as a screening test for detection of pre-clinical ventricular remodeling or dysfunction in the general population has not been established. Here we review available population-based studies assessing the predictive characteristics of BNP for the detection of pre-clinical structural heart disease (Stage B Heart Failure).

Topics: Biological Assay; Disease Progression; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Ventricular Remodeling

B-type natriuretic peptide (BNP) is a cardiac neurohormone which has a principal effect on the kidney to signal both natriuresis and diuresis. Both BNP and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, the relationships between BNP, renal function, and CHF as an emergency diagnosis, are not completely understood. The correlation between BNP and estimated glomerular filtration rate (eGFR) is approximately r = -0.20. At an eGFR < 60 ml/min/1.73 m2, the optimum cutpoint for BNP to diagnose CHF rises to approximately 200 pg/ml. At this cutpoint the area under the receiver operating characteristic curve is 0.81, indicating that BNP is of diagnostic value in this group. Importantly, the precursor molecule N-terminal proBNP has a stronger correlation with eGFR of approximately -0.60, and is influenced by the age-related decline in renal function above the lower bounds of normal of < 60 ml/min/1.73 m2. Because BNP is a principal messenger from the heart to the kidneys, and because it is influenced by renal filtering function, parenchymal mass, and tubular function, BNP can be leveraged in assisting in the diagnosis and management of combined heart and renal failure.

Topics: Biological Assay; Biomarkers; Diuresis; Heart Failure; Humans; Kidney Diseases; Natriuresis; Natriuretic Peptide, Brain; Prognosis; Risk Factors

Cardiac Ischemia is an important trigger for the release of B-type natriuretic peptide (BNP). BNP and N-terminal pro-BNP (N-proBNP) are emerging as important biomarkers for risk stratification in patients with acute coronary syndromes. Higher levels of BNP and pro-BNP are associated with a greater risk for death and heart failure, independent of traditional clinical variables and levels of other biomarkers such as troponins and C-reactive protein. The therapeutic implications of these findings are not yet known.

Topics: Acute Disease; Biological Assay; Biomarkers; Coronary Disease; Heart Failure; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Risk Assessment

The evolving paradigm of heart failure has now been expanded to include the favorable neurohormonal, structural and hemodynamic profile of B-type natriuretic peptide [BNP]. As a marker of left ventricular dysfunction, BNP is a practical tool that facilitates diagnosis, contributes to prognostic evaluations and tracks disease severity. BNP elevations vary according to gender, disease states and perhaps obesity but in general elevated levels are consistent not only with left ventricular stress but likely represent the best surrogate for ongoing left ventricular remodeling. The full utility of BNP surveys has not yet been realized but emerging areas of use include clinical assessment by physician extenders, post-MI assessment, and a target of tailored therapy for heart failure. New biomarkers for heart failure similar to BNP are on the horizon but their clinical niche has yet to be determined.

Topics: Atrial Natriuretic Factor; Biological Assay; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

Heart failure (HF) is a significant clinical and economic burden in the industrialized world. Advances in pharmaceutical compounds and various medical device technologies along with the use of sophisticated HF clinics have enhanced HF treatment and improved morbidity, mortality, and quality of life. However, hospital readmission rates remain stubbornly high. B-type natriuretic peptide (BNP) levels provide valuable information about a patient's chance of readmission within 30 days of discharge, making BNP a potentially useful tool for making discharge decisions and possibly reducing readmissions.. This review examines the strength and level of evidence in key areas to determine if BNP levels could be used as a guide for discharge of HF patients. Although most of the literature describes nonrandomized studies, there is general agreement that BNP levels can be measured accurately and precisely, that BNP levels reflect varying physiologic states, and that they predict outcomes.. More studies are needed to determine extent of biologic variability. The further use of BNP as a potential discharge marker is promising but awaits additional randomized study that reflects use in a broad-based population.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Predictive Value of Tests; Prognosis; Treatment Outcome

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

Nesiritide is a recombinant form of human brain natriuretic peptide (BNP) that is structurally and biochemically identical to endogenously produced BNP. In humans, BNP is important in hemodynamic and neurohormonal equilibrium, helping to maintain adequate vascular volume and pressure in response to volume overload. The pharmacodynamic effects of nesiritide mimic the biologic effects of BNP. The molecular biology and actions of nesiritide and BNP are reviewed, with the therapeutic rationale for nesiritide in patients with acute or advanced decompensated heart failure highlighted. In addition, recommendations for its administration are provided, and unresolved therapeutic considerations are discussed.

Topics: Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Biomarkers; Community Health Services; Echocardiography, Doppler; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Plasma; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Although advances have been made in the management of heart failure (HF), hospital readmission rates remain high. Finding a simple blood test to identify HF would dramatically impact the diagnosis and treatment of this syndrome. A better understanding of the pathophysiology of HF may result in improved treatment measures. Current guidelines do not target any clinical or hemodynamic criteria to achieve before discharge. Most efforts to reduce readmissions have been focused on drugs, technology, and the use of specialty HF clinics. Brain natriuretic peptide (BNP) levels have the potential of providing diagnostic, prognostic, and therapeutic information. In addition, BNP levels appear to be associated with future cardiac events such as hospital readmission. The purpose of this article is to review the precision and accuracy of BNP measurement in those with HF, and to describe how measurement of BNP can be used in clinical practice. Ultimately, BNP testing may improve the accuracy of the diagnosis of HF and guide best treatment practices.

Topics: Clinical Trials as Topic; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Reproducibility of Results; Sensitivity and Specificity; Triage

Heart failure is the leading cause for hospitalization in the United States, resulting in over $8 billion in costs annually. Over 4.8 million Americans are afflicted with the disease and the number is increasing as the baby boomer generation continues to age. It is imperative that new and innovative modalities of therapy and diagnosis evolve as we continue to redefine the nature of heart failure and discover more about this debilitating disease. This article addresses the implications for endogenous brain (B-type) natriuretic peptide (BNP) testing in patients diagnosed with heart failure as well as the implications for the first available form of exogenous BNP, nesiritide. In addition, the pathophysiology of heart failure and traditional treatment modalities are discussed.

Topics: Forecasting; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

The prevalence of heart failure will increase in a number of industrialized countries as the proportion of elderly within the population increases. Despite recent advances in medical and surgical intervention, the prognosis for this disorder has not improved significantly. To make a major impact on the prognosis for heart failure, it would be important to be able to recognize various forms of heart disease before severe heart failure has developed. Chest X-radiography, ECG and echocardiography may not be adequate screening tools for heart failure in large populations. Natriuretic peptides are secreted from the heart in response to various cardiac abnormalities including ventricular dysfunction, volume overload, hypertrophy, and myocardial ischemia. Circulating levels of natriuretic peptides are elevated in various forms of structural cardiac disease regardless of etiology and the degree of ventricular systolic dysfunction. Natriuretic peptides, specifically B-type natriuretic peptide, are practically stable and can be measured without an extraction procedure. We have reviewed the recent status of plasma natriuretic peptide measurement for identification of patients with congestive heart failure, left ventricular dysfunction, and high risk of heart failure, especially in mass screening settings.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Nearly 5 million Americans have heart failure (HF). Making a correct diagnosis early is an important component in the multifaceted approach to detection and/or treatment of this disease. The US Food and Drug Administration recently approved a point-of-care B-type natriuretic peptide assay to be used in the diagnosis of HF. Nesiritide, a synthetic B-type natriuretic peptide, was also approved for use in decompensated HF. B-type natriuretic peptide is released from the cardiac ventricles in response to increased left ventricular volume and/or pressure. This article reviews the nature of this peptide and its potential as a screening tool for HF. It will also present evidence defining the role of B-type natriuretic peptide in the differential diagnosis of dyspnea, prognosis after cardiac events, and in monitoring HF drug therapy.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain

In recent times, there have been many developments in therapies for acute heart failure, in contrast to the preceding 20 years. These have been mainly fueled by new and expanding knowledge about the pathophysiology of heart failure, which has allowed for insight into potential therapeutic strategies. This review will examine the key emerging therapies for acute heart failure, in light of available pathophysiological and clinical evidence.

Topics: Antidiuretic Hormone Receptor Antagonists; Heart Failure; Humans; Hydrazones; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Pyridines; Simendan; Tetrazoles; Treatment Outcome; Vasodilator Agents; Vasopressins

Heart failure is characterized by sodium and fluid retention, sympathetic overactivation, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. New therapies for heart failure attempt to control neurohormonal activation and limit progressive left ventricular dysfunction. Nesiritide (human B-type natriuretic peptide) is a recently approved new vasodilator that has been given to almost 1000 patients in numerous clinical investigations, it belongs to a new class of heart failure drugs known as natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while improving cardiac index, stroke volume and heart failure symptoms. Many endothelin receptor antagonists are in various stages of development. Early clinical studies have demonstrated beneficial cardiovascular hemodynamic effects. Other new drugs for heart failure also include calcium sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosteron receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are being actively investigated and many show significant promise as beneficial therapies in the treatment of heart failure.

Topics: Calcium Channels; Cytokines; Endothelin Receptor Antagonists; Enzyme Inhibitors; Heart Failure; Humans; Natriuretic Peptide, Brain; Neprilysin; Phosphoric Diester Hydrolases; Systole; Vasopressins

Chemotherapy is an established approach for several malignancies, but its utility may be hampered by induced cardiac toxicity possibly leading to heart failure, with a negative impact on the patient's quality of life and ultimately survival. Prospective left ventricular systolic function monitoring has demonstrated that cardiotoxicity could be subclinically present for many months or years before its overt manifestation. Although considered irreversible, some reports suggested recovery or delayed progression of cardiac dysfunction by preventive cardioactive therapies. Thus, the identification of earlier instrumental or biochemical markers of cardiac injury able to predict heart failure remains a major task. Diastolic indexes as a primary expression of hemodynamic dysfunction after cardiac damage, analyzed by means of conventional or newer Doppler technologies (tissue Doppler, color M-mode, etc.) are discussed. Moreover, brain natriuretic peptides, troponins and endothelin-1, as possible sensitive/specific markers/predictors of subclinical cardiotoxicity are reviewed in order to update and possibly improve the strategy for the detection and clinical management of chemotherapy-related cardiotoxic effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cardiac Output, Low; Endothelin-1; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Primary Prevention; Prognosis; Quality of Life; Sensitivity and Specificity; Severity of Illness Index; Troponin; Ventricular Dysfunction, Left

The research on natriuretic peptides in cardiology has now reached the clinical setting in cardiology. The scientific literature on the brain natriuretic peptide (BNP) or on its N-terminal peptide (NT-proBNP) in heart failure is steadily growing, but Italian groups are under-represented in this context, even if there are some published or ongoing studies. This document summarizes the experience, mostly ongoing and unpublished, of 12 Italian groups in that field, as presented in a recent national meeting, suggests recommendations about the collection of blood samples and analytical procedures for BNP assay, and presents a brief consensus on the use of BNP in heart failure, for different areas: a) population screening, b) differential diagnosis of heart failure in case of dyspnea in general practice and c) in the emergency room, d) prognostic stratification in patients with diagnosed heart failure, and e) hormone-guided treatment of heart failure.

Topics: Heart Failure; Humans; Italy; Natriuretic Peptide, Brain; Risk Assessment

Topics: Atrial Fibrillation; Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain

Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure.

Topics: Clinical Trials as Topic; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Natriuretic Agents; Natriuretic Peptide, Brain

Most patients admitted with acute decompensated heart failure (ADHF) go through the emergency department as their initial point of care. New diagnostic tests hold the promise to improve the clinical accuracy of the emergency physicians' diagnosis. Beyond that there is growing recognition that the treatment provided initially has an important impact on the subsequent inpatient course. Basic care for ADHF has involved oxygen as needed, diuretics, and, occasionally, topical or sublingual nitroglycerin. A substantial proportion of patients are treated with vasoactive agents including inotropes and vasodilators such as nitroglycerin and nesiritide. Unfortunately, inotropes have not been demonstrated to improve the outcome of heart failure and, in fact, may be deleterious. The newer agent, nesiritide, has the advantage of being a balanced vasodilator with favorable effects on diuresis, symptom relief, and neurohormones. Evidence from registries indicates that early initiation of nesiritide compared to delayed initiation leads to improved outcomes with shorter lengths of stay, shorter stays in the intensive care unit, and a lower mortality rate. This article reviews the initial management of ADHF, the role of early initiation of vasodilator therapy, and the pharmacoeconomics of nesiritide treatment.

Topics: Decision Trees; Diuretics; Dopamine; Emergency Service, Hospital; Emergency Treatment; Heart Failure; Humans; Length of Stay; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; Oxygen Inhalation Therapy; Practice Guidelines as Topic; United States

Nesiritide is currently indicated for the management of acute decompensated heart failure defined by the presence of volume overload and dyspnea at rest or with minimal activities. Hypotension and cardiogenic shock are the major contraindications to nesiritide use. The recommended dosing schedule is a 2 micro g/kg bolus followed by a 0.01 micro g/kg/min infusion. Some clinicians, however, opt to begin the infusion at the recommended dose without a loading bolus in nonemergency situations. The average duration of infusion in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial was approximately 28 hours. Clinical efficacy endpoints included resolution of dyspnea and reduction of volume overload. Appropriate oral drug therapy for heart failure management should be initiated during the nesiritide infusion. The 15-year transition of B-type natriuretic peptide from a newly discovered physiologic entity to clinical use in the diagnosis and treatment of heart failure provides a remarkable example of rapid technological improvement and enhanced clinical understanding. As with most advances, the process of rolling back the frontiers of knowledge has posed even more questions. However, we must not overlook the progress to date, simply because all of the answers are not yet available.

Topics: Acute Disease; Animals; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Product Surveillance, Postmarketing

Only about half of the diagnoses of heart failure are correct. The limitations of clinical judgment and complementary investigations are described in this article. Recently, BNP was found to be a good biological marker of ventricular dysfunction. Rapid and reliable BNP measurement is now available and the clinical value of this peptide was examined in many studies. The role of BNP in the diagnosis and management of heart failure will be increasing.

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity

Natriuretic Peptides like BNP or NT Pro BNP are diagnostic and prognostic makers largely used in clinical practice. Ageing may increase these peptides, especially in case of comorbidities like renal failure or hypertension and require adjustment for age. Diagnostic value of natriuretic peptides seems however preserved in elderly people.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Electrocardiography; Female; Fluorescent Antibody Technique; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Radioimmunoassay; Reference Values; Sex Factors; Time Factors

The use of BNP as a diagnostic and therapeutic tool in the management of heart failure is promising. Additional studies need to be done regarding the use of BNP as a diagnostic tool to clarify its intrapatient and interpatient variability, especially over time. Nesiritide is the first new intravenous agent for the treatment of acute decompensated heart failure since the introduction of milrinone. It is an effective vasodilator and enhances the effect of concomitant diuretic therapy. Nesiritide may have some benefit on long-term outcomes by prolonging survival, decreasing hospitalizations, or enhancing quality of life. Whether it can or should be used as chronic therapy in end-stage patients remains to be determined.

Topics: Cardiotonic Agents; Diuretics; Drug Therapy, Combination; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Patient Admission; Patient Selection; Sensitivity and Specificity; Treatment Outcome; Vasodilator Agents

Congestive heart failure (CHF) is a disease condition that is increasing in prevalence and is associated with significant morbidity and mortality. Left ventricular systolic dysfunction (LVSD) is a treatable precursor of CHF, but remains asymptomatic in about half of the individuals afflicted. This observation has spurred interest in screening for LVSD. Plasma B-type natriuretic peptide (BNP) is a widely accepted test for the diagnosis of overt CHF. In this review, we examine the potential role for plasma BNP as a screening tool for asymptomatic LVSD. The performance of any screening test depends on its accuracy, the prevalence of the disease condition screened for, and the availability of resources for follow-up of individuals in whom the disease was detected. In the context of community-wide screening for LVSD, a test with high specificity would be important so as to minimize the costs of expensive definitive follow-up tests (i.e. echocardiography). The prevalence of significant LVSD (ejection fraction 20.40) is low, limiting the enthusiasm for a screening program targeting the general population. This is especially true for women, in whom the condition is rare, and the performance characteristics of plasma BNP are sub-optimal. In men, plasma BNP may be a useful screening test in high-risk individuals in whom there are no other clinical indications for echocardiography. The choice of the appropriate plasma BNP threshold that triggers further work-up in such high-risk individuals may vary according to the availability of resources, and with the healthcare priorities of a community.

Topics: Biomarkers; Female; Heart Failure; Humans; Male; Mass Screening; Natriuretic Peptide, Brain; Risk Factors; Systole; Ventricular Dysfunction, Left

Each year, more than 1 million hospitalizations are the result of heart failure. Acute exacerbations of heart failure can occur following routine surgical procedures. One of the newest pharmacological therapies for heart failure is nesiritide. The PACU nurse's vital role in the early recognition and early intervention of heart failure may include the administration of this agent.

Topics: Acute Disease; Aged; Cholecystectomy; Dose-Response Relationship, Drug; Drug Monitoring; Female; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Nurse's Role; Nursing Assessment; Postanesthesia Nursing; Treatment Outcome

Topics: Clinical Trials as Topic; Diagnosis, Differential; Heart Failure; Hospitalization; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Topics: Diastole; Drug Monitoring; Follow-Up Studies; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction

Topics: Drug Monitoring; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Prognosis

Utility of the dosage of brain natriuretic factor (BNP) in the diagnosis and treatment of heart failure. Congestive heart failure (HF) is the main reason for hospitalisation of elderly patients. HF affects nearly 15% of patients aged 75 years or older. Prognosis after the diagnosis of HF is comparable to that of cancers with 50% survival after 4 years for mild HF and 50% after one year in more severe cases. Systolic HF defined by a left ventricular ejection fraction (LVEF) < 40% is asymptomatic in half the patients. In patients with symptomatic HF, LVEF is normal in almost 50% of the cases suggesting a diastolic HF. BNP is secreted after distension of left ventricule mainly in patients with systolic or diastolic HF, in proportion to the severity of the disease. A serum level of BNP > 100 pg/ml has a sensitivity of 90 percent and a specificity of 76 percent for the diagnosis of HF. Serum BNP is also increased in kidney insufficiency and in cirrhosis. BNP increase has a prognostic value to predict mortality after cardiac failure or myocardial infarction. Except for digoxin, all the drugs used to treat HF decrease serum levels of BNP. In dyspneic patients, serum levels of BNP < 50 pg/ml can exclude HF with a good probability. However BNP determination is not useful to diagnose HF in a general population.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain

As there is no cure in patients with Duchenne muscular dystrophy (DMD) yet, we must pay attention to manage cardiopulmonary complications in DMD. They died at 18.2 years old in 1984 in my hospital. From autopsy findings, respiratory failure occupied 75%, and left-sided heart failure occupied 12.5%. First of all, we had to know the relationship between cardiac system and respiratory system. Right-sided heart catheterization revealed that respiratory failure patients were divided into Forrester's subset 1 (left ventricular function was within normal limits). So, it is unnecessary to give digitalis and/or diuretics for patients with respiratory failure. They only need respirator treatment. We tried cuirass ventilation since 1984. This respirator elongated their lives about 3 years. Since 1991 NIPPV was introduced in Japan, this treatment elongated their lives about 5.5 years. Nowadays TIPPV with tracheostomy is not first choice of treatment but we select this treatment not so unwillingly as before. As for left-sided heart failure, BNP (brain natriuretic peptide) is now considered useful parameter for left ventricular function. Japanese clinical researcher proposed treatment based on Values of BNP in left-sided heart failure. In 1980s, from the onset of heart failure until death was only 16 months, we feel that better results already accomplished. Kawai reported that average age at death in Japan was 26.8 years old in 2002. Our efforts must be done more and more until cure of this disease can be found.

Topics: Adolescent; Adult; Age Factors; Biomarkers; Cause of Death; Child; Heart Failure; Humans; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain; Positive-Pressure Respiration; Respiratory Insufficiency; Ventricular Function, Left

Congestive heart failure poses significant challenges to physicians with both diagnosis and management. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles. It correlates with ventricular function, NYHA classification, and prognosis. It is extremely useful in the emergency department in patients presenting with acute dyspnea. It has a particularly strong negative predictive value. In addition, it should be important in screening patients for heart diease, either for those who are at high risk (chemotherapy, diabetes) or as a possible screen before echocardiography. In the future, BNP may be used to modulate treatment of patients in the decompensated setting as well as in titrating outpatient therapy.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiotonic Agents; Dyspnea; Emergencies; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

Topics: Aged; Aged, 80 and over; Attitude of Health Personnel; Echocardiography; Europe; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Needs Assessment; Primary Health Care; Professional Practice; Prognosis; Quality of Life; Survival Analysis; Ventricular Dysfunction, Left

During the past two decades, the heart has been known to undergo endocrine action, harbouring peptides with hormonal activities. These, termed "atrial natriuretic peptide (ANP)," "brain natriuretic peptide (BNP)," and "C-type natriuretic peptide (CNP)," are polypeptides mainly produced in the cardiac myocardium, where they are released into the circulation, producing profound hypotensive effects due to their diuretic, natriuretic, and vascular dilatory properties. It is, furthermore, well established that cardiac disorders such as congestive heart failure and different forms of cardiomyopathy are combined with increased expression of ANP and BNP, leading to elevated levels of these peptides in the plasma. Besides the occurrence of natriuretic peptides (NPs) in the ordinary myocardium, the presence of ANP in the cardiac conduction system has been described. There is also evidence of ANP gene expression in nervous tissue such as the nodose ganglion and the superior cervical ganglion of the rat, ganglia known to be involved in the neuronal regulation of the heart. Furthermore, in the mammalian heart, ANP appears to affect the cardiac autonomic nervous system by sympathoinhibitory and vagoexcitatory actions. This article provides an overview of the relationship between the cardiac conduction system, the cardiac innervation and NPs in the mammalian heart and provides data for the concept that ANP is also involved in neuronal cardiac regulation.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Heart; Heart Conduction System; Heart Failure; Humans; Immunohistochemistry; Mammals; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nodose Ganglion; Receptors, Atrial Natriuretic Factor; Superior Cervical Ganglion

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.

Topics: Animals; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Progression of heart failure is related to ventricular remodeling, a process associated to neurohormonal activation. Brain natriuretic peptide (BNP), a member of the natriuretic peptide family, has recently emerged as an important neurohormone in the pathophysiology of heart failure.. In this update, some of the recent advances on the role of BNP in heart failure are summarized. In particular, the role of BNP in diagnosis of heart disease, as a prognostic marker of cardiovascular events and as a possible guide to optimize heart failure therapy is discussed.. Recent results from 4,300 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) confirmed that BNP is the strongest predictor of outcome in heart failure, when compared to other neurohormones and clinical markers. The current use of BNP in the screening and diagnosis of heart failure and its possible future roles are presented.. In recent years, there has been an impressive accumulation of data supporting an important role of BNP as a diagnostic and prognostic marker of heart failure. Development of rapid, accurate and affordable diagnostic methods will allow the routine monitoring of BNP in a wide spectrum of settings, from general practice to controlled clinical trials.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Disease Progression; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

There is a natural physiological decline in pulmonary function and the cardiovascular system with age. In emergency medicine, acute dyspnoea is a common problem among elderly patients. Some causes, such as pulmonary embolism and diastolic heart failure, are probably under-diagnosed. A good clinical history and examination are as important as arterial blood gas analysis, chest radiography and electrocardiography. Few studies have examined acute dyspnoea in elderly patients, except in the setting of pneumonia. Establishing the underlying diagnosis is often difficult because of atypical presentation and the interaction between cardiac and pulmonary underlying functions. This topic describes several respiratory and cardiac diseases presenting as acute dyspnoea, especially "cardiac asthma" and pulmonary embolism. The clinical usefulness of new investigations such as cardiac and lung echography, pulmonary function tests, serum Brain Natriuretic Peptide and thoracic CT scan are discussed. Further studies looking at acute dyspnoea in elderly patients are needed.

Topics: Acute Disease; Aged; Aging; Algorithms; Blood Gas Analysis; Decision Trees; Diagnosis, Differential; Dyspnea; Echocardiography, Doppler; Electrocardiography; Emergency Treatment; Heart Failure; Humans; Medical History Taking; Natriuretic Peptide, Brain; Physical Examination; Pneumonia; Pulmonary Embolism; Pulmonary Medicine; Radiography, Thoracic; Respiratory Function Tests; Tomography, X-Ray Computed

Most of patients with heart failure present a left ventricular systolic dysfunction usually, if not always, associated with a diastolic dysfunction. Clinical manifestations and physical examination allows a presumed diagnosis. Some signs guide toward a systolic heart failure: deviation of cardiac impulse, protodiastolic gallop, functional mitral insufficiency, radiological cardiomegaly associated with signs of postcapillary hypertension, anterior Q wave or complete left bundle branch block. Bed-side dosage of B-type natriuretic peptide is useful to make or exclude the diagnosis of heart failure in patients with acute dyspnea from various causes. Doppler echocardiography is essential to confirm the left ventricular systolic dysfunction and its mechanism: ischemic, valvular or myocardial. The value of shortening fraction is better than eye evaluation. Coronary angiography is indicated when the mechanism of heart failure is unclear and if the patient is relevant to revascularization.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Electrocardiography; Heart Failure; Humans; Natriuretic Peptide, Brain; Systole

For the acutely ill patient presenting to the emergency department with dyspnea, an incorrect diagnosis could place the patient at risk for both morbidity and mortality. The stimulus for B-type natriuretic peptide (BNP) release is a change in left-ventricular wall stretch and volume overload. A rapid, whole-blood BNP assay (Triage BNP Test, Biosite Inc, San Diego, CA) that allows quick evaluation of the dyspneic patient has recently been approved by the U.S. Food and Drug Administration. Preliminary research with this test set the stage for the recently completed "Breathing Not Properly" BNP Multinational Study, a seven-center, prospective study of 1586 patients who presented to the emergency department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. BNP was accurate in making the diagnosis of congestive heart failure (CHF), and levels correlated to severity of disease. Knowledge of BNP levels could have reduced clinical indecision by 74%. Algorithms are being developed for use in the emergency department that take into account other illnesses that might raise BNP levels. BNP levels should be extremely important in ruling out and diagnosing decompensated CHF, as long as baseline "euvolemic" BNP values are known. Finally, in addition to helping assess whether a dyspneic patient has heart failure, BNP levels may also be useful in making both triage and management decisions.

Topics: Atrial Natriuretic Factor; Dyspnea; Emergency Service, Hospital; Emergency Treatment; Heart Failure; Humans; Natriuretic Peptide, Brain

The management of acutely decompensated heart failure in the emergency medical setting poses a major clinical challenge. Acutely decompensated heart failure is characterized by hemodynamic abnormalities and neuroendocrine activation that contribute to heart failure symptoms, end-organ dysfunction, arrhythmias, and progressive cardiac failure. The therapeutic goals in patients presenting with acutely decompensated heart failure are to stabilize the patient, reverse acute hemodynamic abnormalities, rapidly reverse dyspnea and/or hypoxemia caused by pulmonary edema, and initiate treatments that will decrease disease progression and improve survival. Pharmacologic therapies to impact the hemodynamic abnormalities and symptoms in patients with acutely decompensated heart failure include diuretics, inotropic agents, vasodilators, and natriuretic peptides. In patients with acutely decompensated heart failure, it has recently been demonstrated that elevation in left ventricular filling pressure is the hemodynamic abnormality that most directly impacts heart failure symptoms and is highly predictive of increased risk of fatal decompensation and sudden death. Measures of systemic perfusion, arterial pressure, and vascular resistance have not been predictive of symptoms or clinical outcomes. An ideal agent for acute decompensated heart failure would be one that rapidly reduces pulmonary wedge pressure, results in balanced arterial and venous dilation, promotes natriuresis, lacks direct positive inotropic effects, and does not result in reflex neuroendocrine activation.

Topics: Cardiotonic Agents; Diuretics; Emergency Treatment; Heart Failure; Humans; Morphine; Natriuretic Agents; Natriuretic Peptide, Brain; Vasodilator Agents

Nesiritide, the commercially available form of B-type natriuretic hormone, improved the overall clinical status of patients with acutely decompensated congestive heart failure and several indicators of cardiovascular function in randomized trials. In a trial comparing it to a variety of other agents, efficacy was similar, but fewer patients receiving nesiritide required intravenous diuretics. Nesiritide was associated with significantly lower 6-month mortality than dobutamine, which was found to be more proarrhythmic in an open-label trial. Nesiritide also caused a faster and greater improvement in pulmonary capillary wedge pressure than intravenous nitroglycerin. Adverse effects for nesiritide are generally lower than for other vasoactive agents used for heart failure. The primary adverse effect, hypotension, is dose related and causes symptoms in only about 4% of patients at the current recommended dose. Other side effects are minor or occur infrequently.

Topics: Clinical Trials as Topic; Emergency Treatment; Heart Failure; Hemodynamics; Humans; Natriuretic Agents; Natriuretic Peptide, Brain

Sooner or later all heart failure patients will present to the emergency department for medical attention. The American demographic trend of a skyrocketing elderly population coupled with the current heart-failure epidemic means that strategies optimizing emergency department care of heart failure are needed. Safe and effective management has the potential to decrease hospitalizations and intensive care unit admissions, prevent readmissions, and improve the quality of life in the heart-failure patient, as well as relieving some of the economic burden of heart-failure management from the U.S. medical care system. The emergency department observation unit provides a successful venue for the management of decompensated heart failure, and nesiritide offers the promise of shorter hospitalizations, improved quality of life, and better symptom resolution than standard therapy.

Topics: Atrial Natriuretic Factor; Decision Trees; Diuretics; Emergency Treatment; Heart Failure; Humans; Length of Stay; Natriuretic Agents; Natriuretic Peptide, Brain; Nitroglycerin; United States

Topics: Animals; Heart Failure; Humans; Natriuretic Peptide, Brain

Until recently no simple specific test existed for the differentiation of decompensated heart failure from other causes of acute dyspnoea, or to assess the prognosis of patients with severe heart failure or to optimize heart failure therapy in an individual patient. Measurement of B-type natriuretic peptide has become available as an easy-to-per-form bedside test. Several studies have demonstrated it's usefulness in the emergency room to differentiate heart failure from other causes of acute dyspnoea or to guide the complex drug therapy in an individual patient with heart failure. This article gives a short overview on the clinical experience to use BNP-blood levels for the diagnosis and treatment guidance of heart failure.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Diagnosis, Differential; Heart Failure; Humans; Natriuretic Peptide, Brain

There were almost 1 million hospitalizations for heart failure in 1999, representing a 155% increase over the last 20 years, and the treatment of these patients is an important and growing problem. However, currently available therapies, which are based on three basic mechanisms of action (diuresis, exogenous vasodilators, and cyclic adenosine monophosphate-dependent positive inotropes), have significant limitations that have encouraged the development of newer agents. The leading medications for this indication are representatives of three different therapeutic approaches, which include endogenous vasodilatory neurohormones (nesiritide), calcium sensitizers (levosimendan), and neurohormonal antagonists (tezosentan). These three agents represent a new generation of therapeutics for this important medical problem and may provide the means not only to treat symptoms, but also to improve longer-term clinical outcomes.

Topics: Acute Disease; Cardiotonic Agents; Cohort Studies; Heart Failure; Hemodynamics; Humans; Hydrazones; Multicenter Studies as Topic; Natriuretic Agents; Natriuretic Peptide, Brain; Placebos; Pyridazines; Pyridines; Randomized Controlled Trials as Topic; Receptors, Endothelin; Simendan; Tetrazoles; Time Factors; Vasodilator Agents

A simple blood test useful to the diagnosis and follow-up of congestive heart failure would have a favorable impact on the management of a large populations of patients. Several recent studies have demonstrated that blood levels of Brain Natriuretic Peptide (BNP) may be useful for differentiating heart failure from lung disease in patients presenting to emergency department with dyspnea. Furthermore, BNP might serve as screening test for left ventricular dysfunction (systolic and diastolic), correlates with severity of congestive heart failure and is an independent predictor of outcome. Finally, BNP changes correlate with variations of hemodynamic profile induced by therapy and can be used for a noninvasive tailoring of treatment. These findings make this peptide a potential "white count" for patients with suspected or confirmed heart failure.

Topics: Diagnosis, Differential; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Sensitivity and Specificity

Vasopeptidase inhibitors are a group of agents capable of inhibiting neutral endopeptidase and angiotensin-converting enzymes, which leads to potentiation of natriuretic peptide actions and suppression of the renin-angiotensin-aldosterone system. With this distinctively characteristic mechanism, these agents have emerged as a new drug class for management of hypertension and heart failure. Several vasopeptidase inhibitors are under clinical investigation. Omapatrilat is the most studied agent in this class. Clinical studies of omapatrilat in hypertension have consistently shown the agent's effectiveness in a variety of patient populations. In patients with heart failure, omapatrilat significantly improved neurohormonal and hemodynamic status. Long-term effects of omapatrilat in patients with heart failure recently were compared with those of conventional therapy in a large phase II trial. Results of the study appear promising. Large clinical trials are ongoing, and additional information regarding safety and efficacy from these studies may help define the place in therapy for this agent.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Dose-Response Relationship, Drug; Heart Failure; Humans; Hypertension; Lisinopril; Mesylates; Natriuretic Peptide, Brain; Neprilysin; Pyridines; Randomized Controlled Trials as Topic; Thiazepines; Tyrosine

The B-type or brain natriuretic peptide (BNP) assay, a 15-minute bedside blood test, is highly sensitive and fairly specific for diagnosing heart failure and is useful in evaluating suspected heart failure in outpatients and in emergency care. Other uses include screening for left ventricular dysfunction and predicting outcome in patients with an established diagnosis of heart failure or myocardial infarction.

Topics: Biomarkers; Guidelines as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain

Nesiritide (Natrecor), a synthetic formulation of B-type natriuretic peptide (BNP), is the first new parenteral agent to be approved for treating heart failure in more than a decade. In patients hospitalized with decompensated congestive heart failure, nesiritide promptly reduces pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and systemic vascular resistance, resulting in clinical improvement.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Heart Failure; Humans; Natriuretic Peptide, Brain

Since their discovery 20 years ago, the natriuretic peptides have emerged as an important endocrine response to excessive increases in intravascular volume. In a cGMP-dependent fashion, the natriuretic peptides induce a balanced vasodilation, decreasing preload and afterload in states of cardiac impairment and stimulating the excretion of salt and water by the kidneys. Recombinant B-type natriuretic peptide (nesiritide), identical to the principle natriuretic peptide produced by human cardiac ventricles, has just been approved for the treatment of acute decompensated congestive heart failure. Nesiritide has been shown in controlled trials in congestive heart failure to decrease pulmonary capillary wedge pressure, improve cardiac output, stimulate natriuresis and diuresis, and rapidly induce symptomatic relief. As a naturally occurring stress hormone of the heart, with particular rectifying effects on the pulmonary, cardiac and renal vasculatures, B-type natriuretic peptide may prove useful in a variety of cardiovascular disease states.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Cardiotonic Agents; Heart Failure; Humans; Molecular Sequence Data; Natriuretic Peptide, Brain; Recombinant Proteins

Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling molecule. Several membrane forms of the enzyme have been identified up to now. Some of them serve as receptors for the natriuretic peptides, a family of peptides which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play important roles in renal and cardiovascular physiology. These are transmembrane proteins composed of a single transmembrane domain, a variable extracellular natriuretic peptide-binding domain, and a more conserved intracellular kinase homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP, also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), has been studied widely. Its mode of activation by peptide ligands and mechanisms of regulation serve as prototypes for understanding the function of other particulate GC. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding. Gene knockout and genetic segregation studies have provided strong evidence for the importance of GC-A in the regulation of blood pressure and heart and renal functions. GC-B is the main receptor for CNP, the latter having a more paracrine role at the vascular and venous levels. The structure and regulation of GC-B is similar to that of GC-A. This chapter reviews the structure and roles of GC-A and GC-B in blood pressure regulation and cardiac and renal pathophysiology.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiomyopathies; Down-Regulation; Guanylate Cyclase; Heart Failure; Humans; Hypertension; Isoenzymes; Natriuretic Peptide, Brain; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide; Structure-Activity Relationship

B-type natriuretic peptide (BNP) is secreted by overloaded ventricles. Emerging of bedside dosages cause an increasing interest for this peptide as marker in various clinical situations with heart failure. At first, BNP dosage is a potential tool for detecting heart failure and left ventricular dysfunction. BNP has also a powerful and well-established prognosis value in chronic heart failure. In the emergency setting, and mainly about acute dyspnea, low blood BNP level could eliminate diagnosis of congestive heart failure. Moreover, serial measurement of BNP could allow non-invasive hemodynamic monitoring during decompensated heart failure and could also lead cares as need for intensifying treatment. Nevertheless, its daily use in various clinical situations require that cut-off values are refined.

Topics: Biomarkers; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Reference Values; Sensitivity and Specificity; Time Factors

Over the last decade brain natriuretic peptide (BNP) emerged as a cardiac hormone of clinical interest in diagnosis, prognosis and treatment of patients with Heart Failure (HF). The diagnostic potential of BNP is now well established both in patients with suspected HF as well as in patients with asymptomatic left ventricular systolic dysfunction. The prognostic information obtained from BNP levels in HF and acute myocardial infarction patients seems even more promising. Nesiritide is a synthetic peptide, homologous to endogenous BNP. It is a balanced vasodilator with diuretic and natriuretic properties. It decreases the elevated levels of neurohormones resulting from activation of the sympathetic and renin-aldosterone systems in HF. The results of clinical trials involving more than 2000 patients with decompensated HF are now available. In these trials nesiritide was administered by single or repeated bolus injections, as well as by sustained infusions. Nesiritide has been shown to produce a potent, dose-related vasodilator effect that is rapid in onset and sustained during infusion. Balanced vasodilation is reflected by decreases in systemic vascular resistance, pulmonary artery wedge pressure and right atrial pressure. No tachyphylaxis has been observed in these trials. Efficacy of nesiritide in the treatment of decompensated HF has been demonstrated. Trials comparing nesiritide with conventional treatment of decompensated HF showed that nesiritide compares favorably to standard agents. The safety profile has been excellent with a dose-dependent hypotension as the major side effect. Ventricular arrhythmia was not more frequent in patients treated with nesiritide than with placebo. Thus, nesiritide appears to be useful as a first-line agent in the treatment of patients with decompensated HF.

Topics: Animals; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

The pharmacotherapy currently recommended by the American College of Cardiology and the American Heart Association for heart failure (HF) is a diuretic, an angiotensin-converting enzyme inhibitor (ACEI), a beta-adrenoceptor antagonist and (usually) digitalis. This current treatment of HF may be improved by optimising the dose of ACEI used, as increasing the dose of lisinopril increases its benefits in HF. Selective angiotensin receptor-1 (AT(1)) antagonists are effective alternatives for those who cannot tolerate ACEIs. AT(1) antagonists may also be used in combination with ACEIs, as some studies have shown cumulative benefits for the combination. In addition to being used in Stage IV HF patients, in whom it has a marked benefit, spironolactone should be studied in less severe HF and in the presence of beta-blockers. The use of carvedilol, extended-release metoprolol and bisoprolol should be extended to severe HF patients as these agents have been shown to decrease mortality in this group. The ancillary properties of carvedilol, particularly antagonism at prejunctional beta -adrenoceptors, may give it additional benefits to selective beta(1)-adrenoceptor antagonists. Celiprolol and bucindolol are not the beta-blockers of choice in HF, as they do not decrease mortality. Although digitalis does not reduce mortality, it remains the only option for a long-term positive inotropic effect, as the long-term use of the phosphodiesterase inhibitors is associated with increased mortality. The calcium sensitising drug levosimendan may be useful in the hospital treatment of decompensated HF to increase cardiac output and improve dyspnoea and fatigue. The antiarrhythmic drug amiodarone should probably be used in patients at high risk of arrhythmic or sudden death, although this treatment may soon be superseded by the more expensive implanted cardioverter defibrillators, which are probably more effective and have fewer side effects. The natriuretic peptide nesiritide has recently been introduced for the hospital treatment of decompensated HF. Novel drugs that may be beneficial in the treatment of HF include the vasopeptidase inhibitors and the selective endothelin-A receptor antagonists but these require much more investigation. However, disappointing results have been obtained in a large clinical trial of the tumour necrosis factor alpha antagonist etanercept, where no likelihood of a difference between placebo and etanercept was observed. Small clinical trials with re

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antidiuretic Hormone Receptor Antagonists; Atrial Natriuretic Factor; Cardiotonic Agents; Diuretics; Endothelins; Heart Failure; Human Growth Hormone; Humans; Natriuretic Peptide, Brain; Protease Inhibitors; Renin-Angiotensin System; Tumor Necrosis Factor-alpha; Vasodilator Agents

Thus the natriuretic peptides represent an important class of molecules in patients with congestive symptoms. As such, natriuretic peptide measurements can assist in the evaluation of patients with heart failure or to exclude this as a cause in patients with dyspnea. Increasing the levels of natriuretic peptides may offer an important therapeutic advance in patients with heart failure.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type

Pathophysiology of congestive heart failure (CHF) has undergone a remarkable evolution during the last two decades. CHF is now regarded especially as a neurohormonal disease and not only as a cardiocirculatory impairment. Many studies have emphasized that an abnormal neuroendocrine activation precedes the development of clinically recognized heart failure and plays an important pathogenetic role in progression of this disease. In patients with CHF, moreover, circulating levels of some neurohormonal factors have an independent negative prognostic value. More recently immunological and molecular biology studies have also demonstrated the negative effects exerted by some cytokines and by apoptosis. Correction of neurohormonal disorder is the rationale of therapeutical approach to patients with CHF and appears the only way to significantly decrease mortality. In this review the role of neuroendocrine activation in the pathophysiology of CHF is analyzed.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Atrial Natriuretic Factor; Cytokines; Heart Failure; Humans; Natriuretic Peptide, Brain; Neurosecretory Systems; Neurotransmitter Agents; Prognosis; Rats; Renin-Angiotensin System; Risk Factors; Swine; Ventricular Dysfunction, Left

A blood test that would aid in the diagnosis and management of patients with congestive heart failure would have a favorable impact on the staggering costs of the disease. B-type naturetic peptide (BNP) is synthesized in the cardiac ventricles and its release is directly proportional to ventricular volume expansion and pressure overload. Levels of BNP correlate with left ventricular pressure, amount of dyspnea, and the state of neurohumoral modulation. BNP also correlates closely with New York Heart Association classification. A cut point of 100 pg/mL appears to discriminate patients with congestive heart failure from those without congestive heart failure. Measurement of BNP may also be an excellent screening tool for LV dysfunction. Key Words: Natriuretic peptides; neurohormonal; left-ventricular pressure;

Topics: Atrial Natriuretic Factor; Biomarkers; Endpoint Determination; Heart Failure; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF would clearly have a favorable impact on the staggering costs associated with the disease. B-type natriuretic peptide (BNP) may be the first potential "white count" for heart failure. The fact that a point-of-care, rapid assay for BNP has recently been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. Data suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography, and might also be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as assessment of the state of the patient's neurohormonal compensation.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; Sensitivity and Specificity; Ventricular Dysfunction, Left

Patients with acute congestive heart failure generally present with profound fluid retention states and dyspnea due to pulmonary edema. If the condition is not aggressively and appropriately treated, irreversible cardiac decompensation may ensue, leading to cardiogenic shock, multiorgan failure, and death. Intravenous inotropic, vasopressor, and vasodilator therapies have proved effective in initial stabilization of acute heart failure decompensation, but these agents, particularly the traditionally used ones, are generally limited by side effects that can be egregious and include substantive ventricular arrhythmias. Dobutamine has largely replaced agents with rather profound toxicity, such as isoproterenol and epinephrine. The phosphodiesterase-inhibiting agent milrinone, having both vasodilator and inotropic properties, can produce tachycardia and significant ventricular arrhythmias, but has proven quite useful for seriously ill patients. Clinical trials of levosimendan have found a positive inotropic response when the drug is given parenterally; vasodilating properties are also evident. Clinical trials are under way to evaluate the potential benefits of endothelin receptor antagonists when given intravenously. Intravenous administration of nesiritide, a recombinant human B-type natriuretic peptide, has been shown to produce favorable hemodynamic effects, including balanced vasodilation associated with a rapid improvement in clinical symptoms.

Topics: Acute Disease; Heart Failure; Humans; Hydrazones; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Quinolones; Simendan; Treatment Outcome; Vasodilator Agents

Nesiritide is the generic name for recombinant human B-type natriuretic peptide. This drug represents the first of a new class of agents for the treatment of decompensated congestive heart failure. The properties of B-type natriuretic peptide include a balanced arterial and venous vasodilatation and a marked natriuresis and diuresis, making it an excellent drug for the management of heart failure. We review the physiology and pathophysiology of the natriuretic peptides and the clinical data for nesiritide. In addition, the hemodynamic effects of the drug as well as its efficacy and safety in the treatment of heart failure are critiqued. Nesiritide is a new class of therapeutic peptide for the treatment of heart failure that appears to offer unique and safe hemodynamic properties.

Topics: Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Treatment Outcome

The advances in cardiac failure are permanent. In 2000, once again, they concerned all fields of pathology. Complementary information of the epidemiology of the disease in France and Europe has been published. The prevention of sudden death by the implantable defibrillator in hypertrophic cardiomyopathy has been confirmed. The prognostic role of the aetiology of dilated cardiomyopathy has been demonstrated and the distinct clinical entity of acute fulminating viral myocarditis with an excellent long-term prognosis has been identified. New genetic abnormalities have been found in different forms of dilated cardiomyopathy. One of the most important advances concerns the neurohormones and the rise of interest in type B natriuretic peptide, for diagnosis, prognosis, as well as treatment (nesiritide). From the therapeutic point of view, the importance of betablockers has been confirmed, including in severe cardiac failure. The therapeutic value of biventricular stimulation resynchronising the two ventricles seem to be an additional therapeutic opportunity for patients with advanced cardiac failure. The summit of 2000 remains the first cellular transplantation carried out by a Parisian French team.

Topics: Cardiomyopathies; Cell Transplantation; Heart Failure; Humans; Natriuretic Peptide, Brain

Nesiritide (human recombinant B-type natriuretic peptide) binds to receptors in the vasculature, kidney, and other organs to mimic the actions of endogenous natriuretic peptides. Intravenous infusion of nesiritide has been studied in more than 1,700 patients with acute decompensated heart failure (HF). Nesiritide causes potent, dose-related vasodilation that is rapid in onset and sustained for the duration of drug infusion. There is balanced arterial and venous dilation as reflected by decreases in systemic vascular resistance, systemic arterial pressure, pulmonary capillary wedge pressure, right atrial pressure, and mean pulmonary arterial pressure. Vasodilation occurs without a change in heart rate and is associated with increases in stroke volume and cardiac output. Nesiritide may promote diuresis because of a direct natriuretic action, increased cardiac output, and/or decreased aldosterone levels. In patients hospitalized for decompensated HF, nesiritide improves symptoms and is well tolerated. The major adverse effect is dose-related hypotension. Nesiritide is thus an attractive new vasodilator that should be valuable in the treatment of patients hospitalized for acute decompensated HF.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Treatment Outcome; Vasodilation

Brain natiuretic peptide (BNP) is a hormone secreted specifically by the left ventricular myocytes. Its concentration is correlated with the severity of symptomatic or asymptomatic left ventricular dysfunction. The measurement of BNP has several applications from the screening of populations to the monitoring of the effects of treatment and the evaluation of the prognosis of cardiac failure. The emergence of new methods of rapid measurement will enable its usage as a routine investigation in the near future. Large scale clinical trials are, however, required to confirm the hopes raised by this new marker of left ventricular dysfunction.

Topics: Animals; Biomarkers; Heart Failure; Heart Ventricles; Humans; Myocardium; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiovascular System; Central Nervous System; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Radiography; Reproducibility of Results

In the July 1999 issue of this publication, we described the chemical properties, pharmacology and clinical trials involving nesiritide as a therapeutic agent for patients with decompensated heart failure (Exp. Opin. Invest. Drugs) (1999) 8(7):1063--1072). At the time of publication, the US Food and Drug Administration reviewed the clinical experience with the compound and did not approve the drug for clinical use. More data were requested regarding safety issues, comparison with nitroglycerine, onset of effects, need for invasive haemodynamic monitoring and symptomatic improvement. The VMAC Study was designed to address these issues. A dosing regimen, 0.2 microgram/kg bolus followed by 0.01 microg/kg/min continuous infusion, was chosen to provide rapid onset of actions and haemodynamic improvement without a high incidence of symptomatic hypotension. Nesiritide was superior to iv. nitroglycerine in its haemodynamic effects, easier to administer without the need for dose titration and better tolerated overall. The drug could be administered safely without the need for invasive haemodynamic monitoring. Symptomatic hypotension occurred in 4% of patients. Beneficial haemodynamic effects correlated with symptomatic improvement in heart failure patients. Nesiritide appears to be an ideal first-line agent for treatment of patients with acutely decompensated heart failure.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Peptide, Brain

Heart failure is emerging as a major component of the public health problem of cardiovascular disease as we move into the twenty-first century. Current statistics indicate 4.9 million US citizens are afflicted with direct treatment costs estimated to be $18.8 billion per year. These figures are expected to worsen substantially as the prevalence of heart failure continues to increase. Epidemiologic studies also point to important increases in morbidity and have identified risk factors that aid in prognosis and that may contribute to our mechanistic understanding of heart failure pathophysiology. In addition, epidemiologic results indicate that many patients with mild-to-moderate clinical heart failure are still at substantial risk for morbidity and mortality during follow-up periods of only a few years. These data highlight the importance of enhancing physician and public awareness of heart failure. New methods of molecular epidemiology will point toward better and earlier detection of this common and frequently fatal condition.

Topics: Age Distribution; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Diastole; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Molecular Epidemiology; Natriuretic Peptide, Brain; Prevalence; Prognosis; Risk Factors; Severity of Illness Index; Sex Distribution; Survival Rate; Systole; United States; Ventricular Dysfunction

Finding a simple blood test to aid in the diagnosis and treatment of patients with congestive heart failure could have a favorable impact on the costs associated with the disease. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles, and its level correlates with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation, thus making peptide the first potential "white count" for heart failure. Data indicate that serial point-of-care testing of BNP should be helpful in patients presenting to urgent care clinics with dyspnea. BNP may also serve as a screen for patients referred for echocardiography. A low BNP level makes left ventricular dysfunction (both systolic and diastolic) highly unlikely. BNP may also provide an effective means of improving in-hospital management of patients admitted with decompensated congestive heart failure. In some cases, BNP level observations may obviate the need for invasive hemodynamic monitoring and, when such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as in assessing the state of neurohormonal compensation of the patient.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiotonic Agents; Heart Failure; Hematologic Tests; Humans; Natriuretic Peptide, Brain

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Cattle; Dogs; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; RNA, Messenger; Swine; Vasodilation

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptides; Sodium; Vasoconstriction; Vasopressins

The long-predicted endocrine function of the heart has been proven by the discovery of atrial natriuretic peptide (atrial natriuretic factor, A-type natriuretic peptide; ANP) 20 years ago. This subsequently led to the description of a whole family of structurally similar but genetically distinct peptides, the natriuretic peptide family, which contributes to cardiovascular homeostasis. These looped peptides promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues. Two members, ANP and brain natriuretic peptide (B-type natriuretic peptide; BNP) are secreted by the heart mainly in response to myocardial stretch induced by volume load. The natriuretic peptides are synthesized as preprohormones. The C-terminal endocrinological active peptides (ANP, BNP) and their N-terminal prohormone fragments are found in plasma. The natriuretic peptide system is activated to its highest degree in ventricular dysfunction. However, natriuretic peptides are increased in all patients with edematous disorders which lead to an increase in atrial tension or central blood volume, such as renal failure or ascitic liver cirrhosis. It could be demonstrated that in chronic heart failure patients and during the subacute phase of myocardial infarction, of all tested neurohormones, the cardiac natriuretic peptides were best markers to identify heart failure and the most powerful predictors of morbidity and mortality. Natriuretic peptides are independent markers for risk assessment. In comparative studies BNP was superior to ANP and its N-terminal prohormone fragments in myocardial infarction as well as in chronic heart failure patients. Less data on N-terminal proBNP (NT-proBNP) is available, but BNP and NT-proBNP appear to be equivalent markers. For primary care physicians natriuretic peptide measurement is useful to decide which patient with suspected heart failure warrants further investigation, particularly when assessment of left ventricular function is not readily available. Natriuretic peptides have an excellent negative predictive value, particularly in high risk patients. An increase in BNP is serious enough to warrant follow-up examinations. For the cardiologists the natriuretic peptides are helpful for guidance of therapy and monitoring disease course in heart failure patients and for risk stratification in heart failure and myocardial infarction.

Topics: Atrial Natriuretic Factor; Chemistry, Clinical; Dimerization; Heart Failure; Humans; Models, Biological; Natriuretic Peptide, Brain; Reference Values; Risk Factors

Plasma levels of ANP and BNP increase in accordance with the severity of the heart failure. In severe cases, the amount of BNP secreted surpasses that of ANP. The main secretion site of BNP is the ventricles, and that of ANP is the atria. However, ANP is also secreted from the ventricles as heart failure advances, and thus the ventricles are important sites for both BNP and ANP. It is well known that myocardial stretch is a key factor in the stimulation of the secretion of ANP and BNP, although neurohumoral factors also play a role in the secretion mechanism. The major physiological effects of ANP and BNP are vasodilation, natriuresis, and inhibition of the renin-angiotensin-aldosterone (RAA) and the sympathetic nervous systems; all of which are supposed to suppress the progression of heart failure. The inhibitory action of ANP and BNP on the RAA system has been considered to be an extra-cardiac effect. We recently reported the activation of an angiotensin-converting enzyme and aldosterone production in failing human hearts. ANP and BNP, however, would inhibit aldosterone production, not only in the adrenal cortex but also in cardiac tissue. ANP, and especially BNP, are useful markers of the heart's status during treatment for heart failure. The infusion of synthetic ANP (hANP) or BNP (Nesiritide) is effective in the treatment of acute heart failure. In Japan, BNP occupies an important position in the diagnosis of chronic heart failure, as ANP does in the treatment of acute heart failure.

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Myocardium; Natriuretic Peptide, Brain

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiovascular System; Central Nervous System; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Radiography; Reproducibility of Results

The heart is increasingly being recognised as a major endocrine organ involved in haemodynamic homeostasis. Natriuretic peptides, i.e. atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), affect renal, adrenal and central nervous system functions as well as vessel tonus and permeability thus causing decreased preload and afterload. Natriuretic peptides, BNP in particular, are independent risk factors for morbidity and mortality. They also have high negative predictive values for cardiac insufficiency indicating high diagnostic sensitivity for heart failure in outpatient practice. Monitoring of therapy for heart failure may be improved if BNP measurement is used in conjunction with clinical assessment. However, several problems remain to be solved, such as optimal decision limits in relation to sex and age for the assessment of heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Drug Monitoring; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis

The cardiac natriuretic peptides constitute a family of peptides that regulate fluid homeostasis as well as vascular tonus and growth. Following the fundamental establishment of the heart as an endocrine organ in the early 1980's, the cardiac natriuretic peptides have today been identified as potent biochemical tools in diverse aspects of clinical cardiology including as diagnostic, therapeutic and prognostic markers of cardiac dysfunction as well as potential drug targets. In man, Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are mainly synthesised and secreted by the failing heart, whereas the closely related C-type Natriuretic Peptide (CNP) appears to be a local factor secreted by the endothelium and hence is not considered as a cardiac natriuretic peptide. With the ongoing development of sensitive immunoassays, increased plasma concentrations of ANP and BNP peptides have been associated to a variety of cardiac diseases--but their clinical usefulness as biochemical markers in congestive heart failure is the most promising. In contrast to the large quantity of clinical research on cardiac-derived peptides, the basic understanding of the molecular heterogeneity of these peptides is however still insufficient. Since much clinical work on peptides derived from the proBNP precursor has been published recently, this mini-review will focus on these novel peptides and their potential applications in the clinical setting.

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Heart Failure; Humans; Immunoassay; Molecular Sequence Data; Natriuretic Peptide, Brain; Protein Precursors

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF clearly would have a favorable impact on the staggering costs associated with the disease. BNP, which is synthesized in the cardiac ventricles and correlates with LV pressure, amount of dyspnea, and the state of neurohormonal modulation, makes this peptide the first potential "white count" for heart failure. The fact that a point-of-care rapid assay for BNP has been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. The author's data, and data from others, suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography. A low BNP level makes echocardiographic indices of LV dysfunction (systolic and diastolic) highly unlikely. BNP also might be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. In some instances, BNP levels may obviate the need for invasive hemodynamic monitoring and, in cases where such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies and in assessment of the state of neurohormonal compensation of the patient.

Topics: Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

The important neuroendocrine systems involved in heart failure are reviewed with special emphasis on their possible role in pathophysiology and their relation to prognostic and diagnostic information. Plasma levels of noradrenaline (NA), renin, vasopressin, endothelin-1, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and tumour necrosis factor-alpha (TNF-alpha) are all elevated in heart failure. Activity of the sympathetic nervous system as reflected by NA is correlated to mortality and seems to possess independent prognostic information. Several studies have now documented the beneficial effect of beta-blockade in chronic heart failure (CHF). Renin seems to be a poor prognostic marker in CHF possibly because of the interference with diuretic treatment, angiotensin converting enzyme (ACE)-inhibitors and angiotensin II antagonist, and probably also because of the significance of tissue renin-angiotensin system (RAS), poorly reflected by plasma renin. On the other hand, several large-scale trials with ACE-inhibitors and angiotensin II antagonists have demonstrated reduced mortality and morbidity in CHF. Plasma vasopressin does not seem to possess prognostic information but testing of non-peptide antagonists is ongoing. Endothelin-1 seems to have independent prognostic information and endothelin receptor antagonists may represent a therapeutic possibility. The natriuretic peptides ANP and BNP are correlated to prognosis and possess independent information. Brain natriuretic peptide and N-terminal ANP seem to increase early, i.e. in asymptomatic heart failure. Plasma BNP being more stable than ANP is therefore a promising measure of left ventricular dysfunction. Increase in ANP and BNP, potentially beneficial, may be achieved by administration of neutral endopeptidase inhibitors, at present an unsettled therapeutic possibility. Several cytokines are increased in heart failure and especially TNF-alpha has drawn attention. Experimental studies suggest that TNF-alpha is important in the pathophysiology of heart failure and preliminary studies indicate that inhibition of TNF-alpha seems to be a possible therapeutic approach. Thus, neuroendocrine markers seem to (i) have a role in diagnosis and classification of heart failure, (ii) be useful in providing a 'neuroendocrine profile' which enlightens different aspects of heart failure, and therefore (iii) in the future probably will be valuable in the choice of medical treatment of the individual p

Topics: Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Endothelins; Heart Failure; Humans; Mortality; Natriuretic Peptide, Brain; Neurosecretory Systems; Prognosis; Renin-Angiotensin System; Tumor Necrosis Factor-alpha

B-type or brain natriuretic peptide (BNP) is a balanced vasodilator with no inotropic nor chronotropic properties. Plasma levels can be used in diagnosis and prognosis of patients with heart failure, hypertension, myocardial infarction, right ventricular dysfunction and cor pulmonale. Intravenous therapy with BNP (nesiritide) in nearly 1000 patients demonstrated significant dose-dependent reductions in pulmonary capillary wedge pressure and systemic vascular resistance, as well as increased cardiac index. Compared to dobutamine, it is not pro-arrhythmic and has no effect on heart rate. Compared to standard therapy, it improves dyspnea by 3 h of therapy and leads to fewer headaches and arrhythmias than the commonly used intravenous agents nitroglycerin and dobutamine, respectively. Current research suggests an important role for use of nesiritide in the treatment of decompensated heart failure.

Topics: Biomarkers; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Pulmonary Wedge Pressure; Randomized Controlled Trials as Topic; Recombinant Proteins; Vascular Resistance; Vasodilator Agents

The endocrine function of the heart is to secrete Atrial and Brain natriuretic -peptides (ANP and BNP). These peptides are biologically active via particulate guanylate cyclases which generate cyclic GMP, the second intracellular messenger. A polysaccharide antagonist, HS-142-1 has been recently described by a Japanese Group. Cyclic GMP is partly secreted from the target cells into the extra cellular medium in which its accumulation is proportional to the concentration of the natriuretic peptide. Neutral Endopeptidase (NEP) is a zinc ectoenzyme involved in the catabolism of natriuretic peptides. NEP is absent in plasma but present on the surface of endothelial and smooth muscle cells. NEP is mainly expressed at the apical pole of the epithelial cells of the proximal tubule in the nephron. Chronic increase in volume and pressure within the cardiac cavities is associated with the oversecretion of natriuretic peptides. This chronic phenomenon involves the recruitment of all the cardiac myocytes to express natriuretic peptide genes. The clinical application of this hyperplasic phenomenon is congestive heart failure, in which the plasma levels of natriuretic peptides correlate with the level of the -hemodynamic stress. Therefore the plasma levels of natriuretic peptides are good pronostic markers in both experimental and human heart failure. The degree of congestive heart failure as well as the plasma levels of ANP and BNP are also -correlated with the plasma and urinary levels of cyclic GMP. The plasma level of -cyclic GMP is correlated with the endothelial concentration of cyclic GMP but not with the cyclic GMP concentration in smooth muscle cells. From these experimental data, we can conclude that plasma cyclic GMP originates from endothelial cells and is related to particulate guanylate cyclase activity. In contrast natriuretic peptides do not modulate vascular wall cyclic GMP content. The natriuretic action of ANP is probably due to the interaction of the filtered peptide with the particulate guanylate cyclase at the apical pole of the epithelial cells. The apparition of peptiduria associated with natriuresis during NEP inhibition provides evidence of the action of the peptide in the urinary compartment. It is also by a urinary pathway via the macula densa that ANP, and its potentiation by NEP inhibition, decreases renin secretion. The fact that plasma levels of ANP and plasma and urine levels of cyclic GMP correlate with the degree of salt retention in c

Topics: Atrial Natriuretic Factor; Cyclic GMP; Heart; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Protease Inhibitors; Vasodilation

The natriuretic family consists out of three molecules that share significant amino acid sequence homologies and a looped motif. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are similar in their abilities to promote natriuresis and diuresis, to inhibit the renin-angiotensin-aldosteroneaxis and to act as vasodilators. The understanding concerning the actions of the C-type natriuretic peptide is incomplete, but this new family member acts as a vasodilator. Plasma levels of ANP and BNP are elevated in patients with unstable angina, acute myocardial infarction, and with congestive heart failure. BNP may be superior to ANP as a prognosticator for risk stratification after myocardial infarction and is independent of left ventricular ejection fraction. ANP and BNP have little therapeutic potential while experimental work as well as clinical trials suggest that the inhibition of the catabolism of natriuretic peptides in particular in combination with ACE-inhibitors may be clinically beneficial.

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Renin-Angiotensin System

Topics: Biomarkers; Heart Failure; Hematologic Tests; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. All three peptides are cleared by the natriuretic peptide-C receptor and degraded by the ectoenzyme neutral endopeptidase 24.11, both of which are widely expressed in kidney, lung, and vascular wall. Recently, a fourth member of the natriuretic peptide, Dendroaspis natriuretic peptide (DNP) has been reported to be present in human plasma and atrial myocardium and is elevated in plasma of human CHF.

Topics: Amino Acid Sequence; Angiotensin II; Animals; Atrial Natriuretic Factor; Heart; Heart Failure; Humans; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; ROC Curve; Sensitivity and Specificity; Signal Transduction

The management of congestive heart failure has undergone a number of modifications over the past 5 to 10 years.. These include assaying the role of inotropic drugs, evaluating the role of phosphodiesterase inhibitors, considering the role of intermittent inotropic infusion in ambulatory patients, and recognizing the importance of angiotensin-converting enzyme inhibitors. Very recently, the important role of angiotensin II receptor blocking agents and the use of beta blockade have provided additional modalities for the control of congestive heart failure. The relative usefulness of such therapy has been reviewed in this article.. The management of congestive heart failure has undergone considerable change with the use of newer and more effective drugs.

Topics: Adrenergic beta-Antagonists; Algorithms; Amiodarone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antihypertensive Agents; Calcium Channel Blockers; Cardiotonic Agents; Diagnosis, Differential; Heart Failure; Humans; Indans; Magnesium Compounds; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Propionates

The heart secrets two different natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which have potent vasorelaxant, diuretic, and natriuretic actions. They are main tools in the body's defense against volume overload and hypertension. The natriuretic peptides (NP) are synthetized as prohormones. The C-terminal endocrinological active peptides and their N-terminal prohormone fragments are found in plasma. The NP system is maximally activated in ventricular dysfunction. However, NP:s are also increased in patients with renal failure or pulmonary hypertension, and increases may be found in arterial hypertension or liver cirrhosis. Among all NP and prohormone fragments currently BNP is the most promising candidate analyte for routine diagnosis. BNP is also superior to other neurohormones for diagnosis of left-ventricular dysfunction (LVD) or estimating prognosis in LVD or during the subacute phase of myocardial infarction. For primary care physicians BNP measurement is useful to decide which patient with suspected heart failure warrants further investigation, particularly when assessment of left ventricular function is not readily available. BNP has an excellent negative predictive value particularly in high risk patients. For the cardiologists the NP:s are helpful for monitoring therapy and disease course in LVD patients and for estimating prognosis in LVD and myocardial infarction patients. There is now sufficient evidence to encourage physicians to gain experience with NP as a supplement in the diagnosis of patients suspected of having heart failure. An increase in BNP is serious enough to warrant follow-up examinations.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Arginine Vasopressin; Atrial Natriuretic Factor; Endothelins; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Prostaglandins; Renin-Angiotensin System; Sympathetic Nervous System; Water-Electrolyte Balance

Congestive heart failure has become a major public health problem. A hallmark of this syndrome is neurohumoral activation, with elevation of natriuretic peptides, in particular atrial natriuretic peptide and brain natriuretic peptide of myocardial origin, which occurs with the onset of ventricular dysfunction. The natriuretic peptide system is important in cardiorenal regulation, specifically in the integrated control of intravascular volume and arterial pressure to maintain optimal circulatory integrity. Several therapeutic approaches have been established to mimic or potentiate the unique cardiovascular and renal beneficial actions of these peptides during heart failure. Recent investigations have also established a diagnostic utility for the natriuretic peptides to diagnose early asymptomatic left ventricular dysfunction. Thus, diagnostic and therapeutic use of the natriuretic peptides is emerging as a new strategy to delay the natural history of progressive heart failure from its earliest phase to chronic congestive heart failure.

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type

1. The major cardiovascular and renal actions of alpha-atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the fact that the heart is strategically located to sense changes in intravascular volume indicate the importance of these peptides in the overall control of the extracellular fluid volume under normal and pathophysiological conditions.2. This review examines the clinical and diagnostic significance of the measurement of plasma natriuretic peptides in diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure. 3. Raised plasma levels of ANP and BNP have repeatedly been found in patients with heart disease originating from diverse causes including tachycardias, valvular stenosis or ventricular dysfunction. The raised circulating levels of natriuretic peptide (ANP, N-terminal proANP and BNP in particular) are associated with (i) raised atrial and pulmonary wedge pressures; (ii) reduced ventricular systolic and diastolic function; (iii) presence (and possibly geometric form) of left ventricular hypertrophy; and (iv) severe myocardial infarction. Although both plasma ANP and BNP are raised in the presence of left ventricular hypertrophy, BNP appears to be a better index of left ventricular hypertrophy.4. Several situations where the measurement of natriuretic peptides may be of benefit in the overall assessment of heart disease are discussed. However, it is emphasized that the measurement of plasma natriuretic peptides alone appears to be of limited value as a specific diagnostic tool, given that raised levels are a consequence of haemodynamic and structural abnormalities arising from diverse pathological processes. Despite these limitations, the major value of plasma natriuretic peptides in the examination of patients with suspected heart disease rests on the premise that: (i) a normal value would not be consistent with cardiac disease; (ii) the presence of markedly raised levels may help to target those for subsequent detailed assessment of underlying cardiac dysfunction; and (iii) markedly raised levels of plasma natriuretic peptides after myocardial infarction can identify those at high risk of death.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Risk Factors

Topics: Atrial Natriuretic Factor; Blood Pressure; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left; Water-Electrolyte Balance

Topics: Adrenergic beta-Antagonists; Cardiotonic Agents; Endothelin Receptor Antagonists; Growth Hormone; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Receptor, Endothelin A

Topics: Adult; Aging; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Child; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Predictive Value of Tests; Prognosis; Protein Precursors

Atrial natriuretic factor (ANF) is a peptide hormone secreted by the atria in response to increased transmural pressure. This peptide is the first of a series of natriuretic hormones which also includes brain natriuretic peptide (BNP). It is destroyed mainly by an ubiquitous enzyme, neutral endopeptidase (NEP). Its main actions are vasodilatation and natriuresis. It is the main physiological agonist of the renin/angiotensin/aldosterone system. In elderly subjects free of cardiovascular disease, baseline concentrations are higher than in younger subjects. In patients with congestive heart disease (CHD), the level of ANF rises due to permanent increased filling pressures. Both atrial and ventricular secretion increase ANF levels which loose their day/night rhythm. ANF is a risk factor independent of mortality, rhythm disorders and acute heart failure in patients with heart failure. BNP is also raised in CHD. There is an inverse correlation between concentration and severity of left ventricule dysfunction. There has been little work on ANF in elderly subjects with CHD. ANF is elevated in these patients and is an independent risk factor for cardiac decompensation. In addition, in very elderly subjects where the diagnosis of CHD is difficult and echocardiography not always possible, assay of BNP could be an interesting diagnostic tool. Currently work on therapeutic possibilities (administration of exogenous ANF, combinations with NEP inhibitor/conversion enzyme inhibitor, ANF/diuretics) have revealed certain problems (short half life of ANF, transient effects, non-specific activity of NEP). The usefulness of ANF and BNP in heart failure in elderly subjects will undoubtedly lie in its capacity to mark disease severity and as a diagnostic tool, particularly in case of acute dyspnoea.

Topics: Age Factors; Aged; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Risk Factors

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Heart Failure; Humans; Molecular Sequence Data; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Topics: Atrial Natriuretic Factor; Catecholamines; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Neurosecretory Systems; Renin; Ventricular Dysfunction, Left

The delicate interplay between vasoconstrictors and vasodilators preserves glomerular filtration in CHF despite marked hypoperfusion. Activation of vasoconstrictive systems seems to depend on the severity and the chronicity of the disease. The importance of renin-angiotensin, sympathetic nerves, vasopressin and counterregulatory ANP, and prostaglandins in CHF has been elucidated. Possible roles of newly identified substances, such as endothelin and EDRF, deserve investigation.

Topics: Animals; Atrial Natriuretic Factor; Dogs; Dopamine; Endothelins; Heart Failure; Kidney; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nitric Oxide; Prostaglandins; Rats; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Imbalance

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Heart Diseases; Heart Failure; Humans; Hypertension; Molecular Sequence Data; Natriuretic Peptide, Brain; Protease Inhibitors

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Topics: Animals; Atrial Natriuretic Factor; Guanylate Cyclase; Heart Failure; Humans; Lung; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Pulmonary Edema; Receptors, Atrial Natriuretic Factor

Topics: Atrial Natriuretic Factor; Creatine Kinase; Heart Failure; Humans; Isoenzymes; Myocardial Infarction; Myosins; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Troponin; Troponin T

Natriuretic peptides family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), while receptors for these natriuretic peptides comprise at least three subtypes, i.e. A-type (GC-A), B-type (GC-B) and C-type (clearance). ANP and BNP are cardiac hormones mainly synthesized and secreted by atria and ventricles, respectively, but CNP is a neuropeptide synthesized by brain. Both A- and B-type receptors contain particulate guanylate cyclase within their molecule and mediate biological function via cyclic GMP as a second messenger, whereas C-type receptor is involved in clearance and metabolism of natriuretic peptides. In heart failure, cardiac expression of both ANP and BNP is augmented with increased circulating levels as a cardiac compensatory mechanism. Pathophysiological significance of natriuretic peptides system in heart failure is discussed.

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Gene Expression; Heart Atria; Heart Failure; Humans; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Receptors, Cell Surface

Atrial natriuretic peptide (ANP) exhibits a favorable pharmacological profile in heart failure. In reduces preload and afterload by its natriuretic and vasodilatatory actions. Furthermore, it reduces the activity of the renin aldosterone system. This peptide is activated in early heart failure. Plasma levels of 1-28-hANP are elevated and they correlate with the clinical stage of heart failure, as well as with hemodynamic abnormalities. However, the efficacy of this cardiac hormone in heart failure is limited by renal resistance. Possible mechanisms are a reduced renal perfusion pressure, a receptor down-regulation or an overactivity of sodium-retaining hormones like the renin aldosterone system, and the sympathetic activity. The brain natriuretic peptide (BNP) is also stimulated in heart failure; however, its role in the pathophysiology of heart failure remains to be determined.

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Structure-Activity Relationship

Sodium restriction is recommended for patients with heart failure (HF) despite the lack of solid clinical evidence from randomized controlled trials. Whether or not sodium restrictions provide beneficial cardiac effects is not known.. The present study is a randomized, double-blind, controlled trial of stable HF patients with ejection fraction ≤ 40%. Patients were allocated to sodium restriction (2 g of sodium/day) vs. control (3 g of sodium/day). The primary outcome was change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 20 weeks. Secondary outcomes included quality of life and adverse safety events (HF readmission, blood pressure or electrolyte abnormalities).. Seventy patients were enrolled. Median baseline sodium consumption was 3268 (2225-4537) mg/day. Adherence to the intervention based on 24-hour urinary sodium was 32%. NT-proBNP and quality of life did not significantly change between groups (p > 0.05 for both). Adverse safety events were not significantly different between the arms (p > 0.6 for all). In the per protocol analysis, patients who achieved a sodium intake < 2500 mg/day at the intervention conclusion showed improvements in NT-proBNP levels (between-group difference: -55%, 95% confidence interval -27 to -73%; p = 0.002) and quality of life (between-group difference: -11 ± 5 points; p = 0.04). Blood pressure decreased in patients with lower sodium intake (between-group difference: -9 ± 5 mmHg; p = 0.05) without significant differences in symptomatic hypotension or other safety events (p > 0.3 for all).. Adherence assessed by 24-hour natriuresis and by the nutritionist was poor. The group allocated to sodium restriction did not show improvement in NT-proBNP. However, patients who achieved a sodium intake < 2500 mg/day appeared to have improvements in NT-proBNP and quality of life without any adverse safety signals.. gov Identifier: NCT03351283.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Sodium; Sodium, Dietary; Stroke Volume

Carvedilol demonstrated therapeutic benefits in patients with heart failure and reduced ejection fraction (HFrEF). However, it had a short half-life time mandating twice a day administration. We investigated whether slow-release carvedilol (carvedilol-SR) is non-inferior to standard immediate-release carvedilol (carvedilol-IR) in terms of clinical efficacy in patients with HFrEF.. We randomly assigned patients with HFrEF to receive carvedilol-SR once a day or carvedilol-IR twice a day. The primary endpoint was the change in N-terminal pro B-natriuretic peptide (NT-proBNP) level from baseline to 6 months after randomization. The secondary outcomes were proportion of patients with NT-proBNP increment > 10% from baseline, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.. A total of 272 patients were randomized and treated (median follow-up time, 173 days). In each group of patients taking carvedilol-SR and those taking carvedilol-IR, clinical characteristics were well balanced. No patient died during follow-up, and there was no significant difference in the change of NT-proBNP level between two groups (-107.4 [-440.2-70.3] pg/mL vs. -91.2 [-504.1-37.4] pg/mL, p = 0.101). Change of systolic and diastolic blood pressure, control rate and response rate of blood pressure, readmission rate, and drug compliance rate were also similar. For safety outcomes, the occurrence of adverse reactions did not differ between carvedilol-SR group and carvedilol-IR group.. Carvedilol-SR once a day was non-inferior to carvedilol-IR twice a day in patients with HFrEF.. ClinicalTrials.gov: NCT03209180 (registration date: July 6, 2017).

Topics: Biomarkers; Carvedilol; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Quality of Life; Stroke Volume

Alignment between clinician-reported New York Heart Association (NYHA) class compared and patient-reported outcomes among patients hospitalized for heart failure is unclear.. ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was a global randomized trial comparing nesiritide versus placebo among patients hospitalized for heart failure, irrespective of ejection fraction. Among patients with complete baseline data for NYHA class and the patient-reported EuroQOL-5 dimensions ([EQ-5D], both utility index and visual analog scale), levels of each scale were mapped across 4 prespecified categories "best" to "worst." Minor and moderate-severe discordance were defined as NYHA class and EQ-5D differing by 1 level and ≥2 levels, respectively. Multivariable models assessed factors independently associated with moderate-severe discordance, and associations between discordance and clinical outcomes.. gov; Unique identifier: NCT00475852.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; New York; Patient Reported Outcome Measures; Quality of Life; Treatment Outcome

Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. It remains unclear whether the decongestive effects of acetazolamide differ across the spectrum of left ventricular ejection fraction (LVEF).. This is a prespecified analysis of the randomized, double-blind, placebo-controlled ADVOR trial that enrolled 519 patients with acute heart failure (HF), clinical signs of volume overload (eg, edema, pleural effusion, or ascites), NTproBNP (N-terminal pro-B-type natriuretic peptide) >1000 ng/L, or BNP (B-type natriuretic peptide) >250 ng/mL to receive intravenous acetazolamide (500 mg once daily) or placebo in addition to standardized intravenous loop diuretics (twice that of the oral home maintenance dose). Randomization was stratified according to LVEF (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload within 3 days from randomization without the need for mandatory escalation of decongestive therapy because of poor urine output.. Median LVEF was 45% (25th to 75th percentile; 30% to 55%), and 43% had an LVEF ≤40%. Patients with lower LVEF were younger and more likely to be male with a higher prevalence of ischemic heart disease, higher NTproBNP, less atrial fibrillation, and lower estimated glomerular filtration rate. No interaction on the overall beneficial treatment effect of acetazolamide to the primary end point of successful decongestion (OR, 1.77 [95% CI, 1.18-2.63];. When added to treatment with loop diuretics in patients with acute decompensated HF, acetazolamide improves the incidence of successful decongestion and diuretic response, and shortens length of stay without treatment effect modification by baseline LVEF.. URL: https://www.. gov; Unique identifier: NCT03505788.

Topics: Acetazolamide; Diuretics; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

To investigate the effect of left ventricular ejection fraction (LVEF) on the behavior of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with heart failure and type 2 diabetes mellitus with the use of canagliflozin compared to glimepiride.. Patients (n = 233) from the CANDLE trial were randomly assigned to either the add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The patients were followed-up for 24 weeks. The NT-proBNP levels were measured at baseline and after 24 weeks. The LVEF was determined at baseline.. There was a significant relationship between the baseline NT-proBNP level (X1) and the change in NT-proBNP levels from baseline to 24 weeks (Y) in the canagliflozin group (Y = -0.533 × X1 + 178; r = -0.860, p < 0.001). However, this relationship was not observed in the glimepiride group (p = 0.428). The baseline LVEF (X2) correlated with Y with a marginal significance in the canagliflozin group (Y = 7.72 × X2-549; r = 0.192, p = 0.054), but no relationship was observed in the glimepiride group. In the canagliflozin group, bivariate regression analysis showed a significant correlation between Y, X1, and X2; Y = -0.567 × X1-6.04 × X2 + 542 (R = 0.871, p < 0.001). The partial regression coefficients of X1 (p < 0.001) and X2 (p = 0.006) significantly explained the variance in Y. The correlation coefficient for X2 was negative. There was a significant relationship between the logarithmically transformed NT-proBNP [ln(NT-proBNP)] at baseline (X1') and the change in ln(NT-proBNP) values from baseline to 24 weeks (Y'), a surrogate of the rate of change in NT-proBNP levels, in the canagliflozin group (Y' = -0.18 × X1' + 0.93; r = 0.450, p = 0.001).. The baseline NT-proBNP level significantly affected the extent and the rate of its decrease by canagliflozin. The reduction in NT-proBNP levels by canagliflozin was prominent in patients with a higher LVEF at baseline. However, its confounding effect of LVEF on canagliflozin treatment was not recognized without adjusting for the NT-proBNP level at baseline.

Topics: Biomarkers; Canagliflozin; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling.. Here we examined both clinical and mechanistic relationships between PAGln and heart failure (HF). First, we examined associations among plasma levels of PAGln and HF, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 2 independent clinical cohorts of subjects undergoing coronary angiography in tertiary referral centers (an initial discovery US Cohort, n=3256; and a validation European Cohort, n=829). Then, the impact of PAGln on cardiovascular phenotypes relevant to HF in cultured cardiomyoblasts, and in vivo were also examined.. Circulating PAGln levels were dose-dependently associated with HF presence and indices of severity (reduced ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide) independent of traditional risk factors and renal function in both cohorts. Beyond these clinical associations, mechanistic studies showed both PAGln and its murine counterpart, phenylacetylglycine, directly fostered HF-relevant phenotypes, including decreased cardiomyocyte sarcomere contraction, and B-type natriuretic peptide gene expression in both cultured cardiomyoblasts and murine atrial tissue.. The present study reveals the gut microbial metabolite PAGln is clinically and mechanistically linked to HF presence and severity. Modulating the gut microbiome, in general, and PAGln production, in particular, may represent a potential therapeutic target for modulating HF.. URL: https://clinicaltrials.gov/; Unique identifier: NCT00590200 and URL: https://drks.de/drks_web/; Unique identifier: DRKS00020915.

Topics: Animals; Gastrointestinal Microbiome; Heart Failure; Humans; Mice; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Traditional Chinese eight brocade exercise (TCEBE) with same cycle and frequency and different durations has an effect on patients with chronic heart failure (CHF). However, relevant reports on the topic are lacking.. This study aims to explore the differences of rehabilitation effect by conducting TCEBE with the same cycle and frequency and different single exercise time for patients with CHF.. A total of 103 patients with CHF were randomly divided into long-time group (LTG), short-time group (STG) and control group (CG). The subjects in the three groups were given corresponding routine treatment. In addition, under the guidance of professional TCEBE coaches and nurses, TCEBE was conducted for 12 weeks (3 times/week) for LTG (60 min/time) and STG (30 min/time). Minnesota living with heart failure questionnaire (MLHFQ) was used, and 6-min walk (6MWK) and brain nautical peptide (BNP) were tested.. 1) At 12 weeks, the comparison between groups obtained the following results: For the LTG, MLHFQ was less than that of the CG (P < 0.01), 6MWT was greater than that of the CG (P < 0.05), and 6MWT was greater than that of the STG (P < 0.05); for the STG, MLHFQ was less than that of the CG (P < 0.05); no significant difference in BNP was found among the three groups; 2) At 12 weeks and 0 weeks, the comparison obtained the following results: For the LTG, MLHFQ decreased by 37.7 %, and 6MWT increased by 46.7 % (P < 0.01); for the STG, MLHFQ decreased by 31.7 %, and 6MWT increased by 31.5 % (P < 0.01); for the CG, MLHFQ decreased by 14.6 %, and 6MWT increased by 19.7 % (P < 0.05); no significant change in BNP was found in each group.. TCEBE of two kinds of duration improves the quality of life and 6MWT of patients with CHF but has no positive effect on BNP. Compared with 30-min/time, 60-min/time further improves 6MWT in patients with CHF but has no additional benefit on quality of life.

Topics: East Asian People; Exercise; Heart Failure; Humans; Natriuretic Peptide, Brain; Quality of Life; Randomized Controlled Trials as Topic

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF).. The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1-Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80-1.09), > median 0.81 (0.73-0.90) (p-interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) (p-interaction = 0.035). There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (p-interaction = 0.086).. In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL.. ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016-002299-28.

Topics: Atrial Fibrillation; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume

We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels.. This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO. At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO. In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.

Topics: Functional Status; Heart Failure; Hemoglobins; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Quality of Life; Stroke Volume; Ventricular Dysfunction, Left

Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management.. To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF.. The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b-type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included.. Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily.. Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events.. Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04).. In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF.. ClinicalTrials.gov Identifier: NCT04687111.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Female; Heart Atria; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Neprilysin; Stroke Volume; Tetrazoles; Valsartan

Topics: Cardiotonic Agents; Cardiovascular Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Heart Failure; Humans; Natriuretic Peptide, Brain; Recombinant Proteins; Stroke Volume; Ventricular Function, Left

STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared with usual care. The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration.. A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes, from randomization to 1 week later, as decreased (≥30%), stable (<30% decrease to ≤10% increase), or increased (>10%). The primary endpoint was 180-day HF readmission or death. The effect of HIC vs. usual care was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months, they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs. 2.2% and 4.0% in those with decreased NT-proBNP (P = 0.039 and P = 0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; P = 0.93).. Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge, utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate, resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change.

Topics: Aftercare; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Prognosis

Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF).. This study sought to assess the clinical implications of RV function, the association with N-terminal pro-B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF.. This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro-B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders.. Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro-B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function.. Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Topics: Aged; Aged, 80 and over; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right

Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients.. Our study is a single-centre, single-blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA-guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during hospitalization and within 90 days after discharge. The BIA-guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT-proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA-guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days.. Among overweight and obese patients with HF, BIA reduces NT-proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA-guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Overweight; Pilot Projects; Single-Blind Method

Remote monitoring of pulmonary artery (PA) pressures and serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements guide heart failure (HF) treatment, but their association has yet to be described.. In the Empagliflozin Evaluation by Measuring the Impact on Hemodynamics in Patients with Heart Failure (EMBRACE-HF) trial, patients with HF and a remote PA pressure monitoring device were randomized to empagliflozin vs placebo. PA diastolic pressures (PADP) and NT-proBNP levels were obtained at baseline and 6 and 12 weeks. We used linear mixed models to examine the association between change in PADP and change in NT-proBNP, adjusting for baseline covariates. Of 62 patients, the mean patient age was 66.2 years, and 63% were male. The mean baseline PADP was 21.8 ± 6.4 mm Hg, and the mean NT-proBNP was 1844.6 ± 2767.7 pg/mL. The mean change between baseline and averaged 6- and 12-week PADP was -0.4 ± 3.1 mm Hg, and the mean change between baseline and averaged 6- and 12-week NT-proBNP was -81.5 ± 878.6 pg/mL. In adjusted analyses, every 2-mm Hg decrease in PADP was associated with an NT-proBNP reduction of 108.9 pg/mL (95% confidence interval -4.3 to 222.0, P = .06).. We observed that short-term decreases in ambulatory PADP seem to be associated with decreases in NT-proBNP. This finding may provide additional clinical context when tailoring treatment for patients with HF.

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery

N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements can be used to rule out heart failure in patients with sinus rhythm. Atrial fibrillation often coexists with heart failure but affects NT-proBNP levels. This study aims to identify the optimal NT-proBNP cut-off value for ruling out heart failure among atrial fibrillation patients.. This prospective study included 409 atrial fibrillation patients admitted to the emergency department. The inclusion criterion was documented atrial fibrillation on a 12‑lead electrocardiogram. All patients completed a NT-proBNP blood sample, a chest X-ray and an echocardiogram. Heart failure was defined as a left ventricular ejection fraction of <40%.. In total, 409 patients were included (mean age: 75.2 ± 11.6). The median NT-proBNP level was 2577 ng/L (quartiles: 1185-5438) and 21% had heart failure. We found a lower median NT proBNP level of 3187 ± 3973 ng/L in patients without heart failure compared to 9254 ± 8008 ng/L in patients with heart failure (absolute difference: 4131, 95% (CI): 3299-4986, p < 0.001). The area under the receiver operating characteristic curve for diagnosing heart failure was 0.82 (95% confidence interval: 0.77-0.87). The optimal cut-off value for ruling out heart failure was 739 ng/L with a sensitivity of 99%, a specificity of 18%, and a negative predictive value of 98%.. NT-proBNP can be used to rule out heart failure in atrial fibrillation patients with a high negative predictive value, but low specificity.. NCT04125966. https://clinicaltrials.gov/ct2/show/NCT04125966.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Function, Left

Long-term benefits of pulmonary artery denervation (PADN) for patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH) secondary to left heart failure are unknown.. The authors sought to report the 3-year clinical results of PADN for patients with CpcPH.. A total of 98 patients with CpcPH, defined as having mean pulmonary arterial pressure of ≥25 mm Hg, pulmonary capillary wedge pressure of >15 mm Hg, and pulmonary vascular resistance of >3.0 WU, were randomly assigned to receive the sham + sildenafil or PADN. The primary endpoint was the occurrence of clinical worsening defined as cardiopulmonary death, rehospitalization or heart/lung transplantation at 3-year follow-up. Changes in the 6-minute walk distance and N-terminal pro-B-type natriuretic peptide served as secondary points.. At the 3-year follow-up, clinical worsening was reported in 49 (50.0%) patients, with 31 (62.0%) in the sham + sildenafil group and 18 (37.5%) in the PADN group (HR: 2.13 [95% CI: 1.19-3.81]; P = 0.011), largely driven by a higher rate of rehospitalization in the sham + sildenafil group (56.2% vs 35.4%; HR: 1.96 [95% CI: 1.07-3.58]; P = 0.029) by Cox proportional hazards regression. At the end of the study, cardiopulmonary-related deaths occurred in 16 (32.0%) patients in the sham and 9 (18.8%) (P = 0.167) patients in the PADN group. PADN also resulted in a more profound increase in the 6-minute walk distance and reduction in N-terminal pro-B-type natriuretic peptide.. PADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes. Further study without approved drugs for pulmonary arterial hypertension is required to confirm the benefits of PADN for patients with CpcPH. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335).

Topics: Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pulmonary Artery; Sildenafil Citrate

The VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) demonstrated that, in patients with high-risk heart failure, vericiguat reduced the primary composite outcome of cardiovascular death or heart failure hospitalization relative to placebo. The hazard ratio for all-cause mortality was 0.95 (95% CI, 0.84-1.07). In a prespecified analysis, treatment effects varied substantially as a function of baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, with survival benefit for vericiguat in the lower NT-proBNP quartiles (hazard ratio, 0.82 [95% CI, 0.69-0.97]) and no benefit in the highest NT-proBNP quartile (hazard ratio, 1.14 [95% CI, 0.95-1.38]). An economic analysis was a major secondary objective of the VICTORIA research program.. Medical resource use data were collected for all VICTORIA patients (N=5050). Costs were estimated by applying externally derived US cost weights to resource use counts. Life expectancy was projected from patient-level empirical trial survival results with the use of age-based survival modeling methods. Quality-of-life adjustments were based on prospectively collected EQ-5D-based utilities. The primary outcome was the incremental cost-effectiveness ratio, comparing vericiguat with placebo, assessed from the US health care sector perspective over a lifetime horizon. Cost-effectiveness was estimated using the total VICTORIA cohort, both with and without interaction between treatment and baseline NT-proBNP.. Life expectancy modeling results varied according to whether the observed heterogeneity of treatment effect by baseline NT-proBNP values was incorporated into the modeling. Including the interaction term, the vericiguat arm had an estimated quality-adjusted life expectancy of 4.56 quality-adjusted life-years (QALYs) compared with 4.13 QALYs for placebo (incremental discounted QALY, 0.43). Without the treatment heterogeneity/interaction term, vericiguat had 4.50 QALYs compared with 4.33 QALYs for placebo (incremental discounted QALY, 0.17). Incremental discounted costs (vericiguat minus placebo) were $28 546 with the treatment interaction and $20 948 without it. Corresponding incremental cost-effectiveness ratios were $66 509 per QALY allowing for treatment heterogeneity and $124 512 without heterogeneity.. Vericiguat use in the VICTORIA trial met criteria for intermediate value, but the incremental cost-effectiveness ratio estimates were sensitive to whether the analysis accounted for observed NT-proBNP treatment effect heterogeneity. The cost-effectiveness of vericiguat was driven by the projected incremental life expectancy among patients in the lowest 3 quartiles of NT-proBNP.. URL: https://www.. gov; Unique identifier: NCT02861534.

Topics: Cost-Benefit Analysis; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Natriuretic Peptide, Brain; Stroke Volume

The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population.. To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms.. A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk.. Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy.. The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy.. Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns.. The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels.. ClinicalTrials.gov Identifier: NCT02816736.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Double-Blind Method; Drug Combinations; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Valsartan

Achievement of decongestion in acute heart failure (AHF) is associated with improved survival and cardiovascular outcomes but can be associated with acute declines in estimated glomerular filtration rate (eGFR). We examined whether the rate of in-hospital decongestion is associated with longer term kidney function decline.. Post hoc analysis of trial data.. Patients with ≥2 measures of kidney function (n = 3,500) from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial.. In-hospital rate of change in assessments of volume overload, including B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and clinical congestion score (0-12); and rate of change in hemoconcentration including measures of hematocrit, albumin, and total protein.. Incident chronic kidney disease GFR category 4 or worse (chronic kidney disease [CKD] categories G4-G5; defined by a new eGFR of <30 mL/min/1.73 m. Multivariable cause-specific hazards models.. Over median 10-month follow-up period, faster decreases in volume overload and more rapid increases in hemoconcentration were associated with a decreased risk of incident CKD G4-G5 and eGFR decline of >40%. In adjusted analyses, for every 6% faster decline in BNP per week, there was a 32% lower risk of both incident CKD G4-G5 (HR, 0.68 [95% CI, 0.58-0.79]) and eGFR decline of >40% (HR, 0.68 [95% CI, 0.57-0.80]). For every 1% faster increase per week in absolute hematocrit, there was a lower risk for both incident CKD G4-G5 (HR, 0.73 [95% CI, 0.64-0.84]) and eGFR decline of >40% (HR, 0.82 [95% CI, 0.71-0.95]), with results consistent for other biomarkers.. Possibility of residual confounding.. These results provide reassurance that more rapid decongestion in patients with AHF does not increase the risk of adverse kidney outcomes in patients with heart failure.

Topics: Biomarkers; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Risk Factors; Water-Electrolyte Imbalance

There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.. Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, <6.0%; (ii) pre-diabetes, 6.0%-6.4%; (iii) diabetes, ≥6.5% or history of diabetes. The primary outcome was a composite of cardiovascular (CV) death and total heart failure hospitalizations (HFH). Of 4796 patients, 50% had diabetes and 18% had pre-diabetes. Compared to patients with normal HbA1c, patients with pre-diabetes and diabetes more often were obese, had a history of myocardial infarction and had lower Kansas City Cardiomyopathy Questionnaire scores, while patients with diabetes had more clinical evidence of congestion, but similar NT-proBNP concentrations. The risks of the primary composite outcome (rate ratio [RR] 1.59, 95% confidence interval [CI] 1.35-1.88), total HFH (RR 1.67, 95% CI 1.39-2.02) and CV death (hazard ratio [HR] 1.35, 95% CI 1.07-1.71) were higher among patients with diabetes, compared to those with normal HbA1c. Patients with pre-diabetes had a higher risk (which was intermediate between that of patients with diabetes and those with normal HbA1c) of the primary outcome (HR 1.27, 95% CI 1.00-1.60) and HFH (HR 1.35, 95% CI 1.03-1.77), but not of CV death (HR 1.02, 95% CI 0.75-1.40). Patients with diabetes treated with insulin had worse outcomes than those not, and those with 'lean diabetes' had similar mortality rates to those with a higher body mass index, but lower rates of HFH.. Pre-diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH.. ClinicalTrials.gov Identifier NCT01920711.

Topics: Diabetes Mellitus; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prediabetic State; Prognosis; Stroke Volume; Ventricular Function, Left

Topics: Animals; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Glomerular Filtration Rate; Heart Failure; Humans; Natriuretic Peptide, Brain; Sodium; Tadalafil

Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes.. The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle.. Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016).. RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.

Topics: Adult; Aged; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; COVID-19; Female; Heart Failure; Hospitals; Humans; Natriuretic Peptide, Brain; Renin-Angiotensin System

Melatonin, the major secretion of the pineal gland, has beneficial effects on the cardiovascular system and might advantage heart failure with reduced ejection fraction (HFrEF) by attenuating the effects of the renin-angiotensin-aldosterone and sympathetic system on the heart besides its antioxidant and anti-inflammatory effects.. We hypothesized that oral melatonin might improve echocardiographic parameters, serum biomarkers, and a composite clinical outcome (including quality of life, hospitalization, and mortality) in patients with HFrEF.. A placebo-controlled double-blinded randomized clinical trial was conducted on patients with stable HFrEF. The intervention was 10 mg melatonin or placebo tablets administered every night for 24 weeks. Echocardiography and measurements of N-terminal pro-B-type natriuretic peptide (NT-Pro BNP), high-sensitivity C-reactive protein, lipid profile, and psychological parameters were done at baseline and after 24 weeks.. Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT-Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2-215.7], p = .044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18-1.69], p = .017), quality of life (5.8 [0.9-12.5], p = .037), and New York Heart Association class (odds ratio: 12.9 [1.6-102.4]; p = .015) at the end of the trial. Other studied outcomes were not significantly different between groups.. Oral melatonin decreased NT-Pro BNP and improved the quality of life in patients with HFrEF. Thus it might be a beneficial supplement in HFrEF.

Topics: Dietary Supplements; Heart Failure; Humans; Melatonin; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Stroke Volume

C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP).. We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2.. NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)15-270 min was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC15-270 min compared with control (P = 0.001) in Trial 2.. Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition.ClinicalTrials.gov registration number NCT03717688.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neprilysin; Peptide Fragments; Sitagliptin Phosphate; Tetrazoles; Valsartan

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

Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone.. Patients with higher LVEF had higher circulating levels of chemokines and inflammatory markers and lower levels of stretch, injury, and fibrosis markers. Spironolactone reduced the circulating levels of natriuretic peptides and type 1 collagen, and increased LVEF.

Topics: Biomarkers; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Spironolactone; Stroke Volume; Tissue Plasminogen Activator; Ventricular Function, Left

We carried out a randomized controlled trial using ipragliflozin. We analyzed changes in diastolic function using echocardiography in patients with type 2 diabetes and heart failure with preserved ejection fraction.. We carried out an open-label, multicenter, randomized, two-arm interventional trial. A total of eligible 68 participants were randomly assigned into two groups (ipragliflozin group n = 36; conventional treatment group n = 32). Primary end-points were the change in E/e' and e'. Secondary end-points were other parameters of echocardiography, plasma NT-proBNP level, New York Heart Association class, hemoglobin A1c and blood pressure.. After 24 weeks of follow up, E/e' decreased in both groups (ipragliflozin: 11.0 vs 10.4; conventional treatment 10.5 vs 10.1; multivariate-adjusted P = 0.95). There were no significant differences in the amount of change in E/e', e', echocardiography parameters, plasma NT-proBNP level, New York Heart Association class, hemoglobin A1c and blood pressure between the two groups. In the subgroup analysis, ipragliflozin treatment decreased in left ventricular mass index in patients aged ≥70 years and also decreased in NT-proBNP levels in patients with baseline NT-proBNP ≥400 pg/mL.. In this randomized controlled study carried out in patients with type 2 diabetes and heart failure with preserved ejection fraction, 24-week ipragliflozin treatment did not improve left ventricular diastolic function compared with conventional treatment. As the subgroup, ipragliflozin treatment decreased in left ventricular mass index in participants aged ≥70 years. Geriatr Gerontol Int 2022; 22: 298-304.

Topics: Aged; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Thiophenes; Ventricular Function, Left

Sacubitril valsartan and valsartan are the first new drugs approved for angiotensin receptor neprilysin lysine inhibitors (ARNIs) in outpatients with chronic heart failure (CHF) and hypertension. Compared with enalapril, sacubitril valsartan and valsartan have been shown to reduce the mortality and morbidity of cardiovascular diseases. However, there is little actual evidence regarding the efficacy of ARNIs in hypertensive patients with CHF.. From January 2019 to January 2021, 60 patients with hypertension and chronic heart failure were diagnosed and treated in our hospital. The patients were randomly divided into an observation group and a control group, with 30 cases in each group. The control group was given valsartan, the observation group was given sacubitril valsartan, and both groups were treated for six months. The endothelium-dependent vasodilation (EDD) function of the brachial artery and serum nitric oxide (NO), endothelin-1 (ET-1), carotid artery intima-media thickness, and glomerular filtration, excess rate (eGFR), and left ventricular ejection fraction (LVEF) were compared between the two groups of patients before and after treatment. The serum adiponectin (APN), matrix metalloproteinase-9 (MMP-9), and brain natriuretic peptide (BNP) levels were compared before and after treatment.. The total effective rate of treatment in the research group was higher than that in the control group (. In the treatment of hypertension and chronic heart failure, sacubitril valsartan can improve the clinical symptoms of patients to the greatest extent and can significantly improve the levels of LVEF, LVEDD, NT-proBNP, heart function, and other indicators. Sacubitril valsartan can increase serum APN levels, reduce MMP-9 and BNP levels, and have good clinical effects. Sacubitril valsartan has a protective effect on the vascular endothelial function of patients with hypertension and CHF. However, these results need to be confirmed in studies involving more subjects and require longer follow-up times.

Topics: Adiponectin; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Carotid Intima-Media Thickness; Drug Combinations; Endothelium; Heart Failure; Humans; Hypertension; Matrix Metalloproteinase 9; Natriuretic Peptide, Brain; Stroke Volume; Treatment Outcome; Valsartan; Ventricular Function, Left

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

In this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level.. In the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation.. In the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause.. All 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (P. Lower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945).

Topics: Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Denmark; Follow-Up Studies; Heart Failure; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments

This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials.. The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF).. Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo.. DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213]).

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left

Currently, standard medical therapies have limited effects on heart failure with preserved ejection fraction (HFpEF), which impacts on the life quality and survival of patients. This study aimed to evaluate the safety and efficacy of the percutaneous radiofrequency ablation-based interatrial shunting for HFpEF with a novel atrial septostomy device.. A preclinical study in 11 normal domestic pigs and the first-in-man study in 10 patients with HFpEF were performed. The major safety events and interatrial shunt performance were evaluated at baseline, 1 month, 3 months, and 6 months post-procedure in both animals and human patients. The clinical functional status was also assessed in the first-in-man study.. Percutaneous radiofrequency ablation-based interatrial shunting therapy was performed successfully both in animals and patients. In the animal study, a left-to-right interatrial shunt was created with a mean defect size of 5.5±2.2 mm without procedure-related safety events. Seven pigs showed the continuous shunting with a mean defect size of 4.1±1.5 mm at 6 months. In the first-in-man study, a median interatrial defect diameter of 5.0 (4.0-6.0) mm was measured immediately. No major safety events including death and thromboembolism were observed. The continuous shunting with the defect size of 4.0 (3.0-4.0) mm could still be observed in 7 patients at 6 months. The clinical status was significantly improved with NT-proBNP (N-terminal pro-B-type natriuretic peptide) reduced by 2149 pg/mL ([95% CI, 204-3301]. The present results showed that percutaneous radiofrequency ablation-based interatrial shunting was a safe and potentially effective therapy for HFpEF, providing a nonpharmacological and nonimplanted option for HFpEF management.. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900027664.

Topics: Animals; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prostheses and Implants; Quality of Life; Stroke Volume; Swine

Patients with heart failure (HF) and reduced ejection fraction suffer from a relapsing and remitting disease course, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multisensor index and alerts in HF care.. The Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HF and reduced ejection fraction (<35%), New York Heart Association functional class II-III symptoms, implanted with a cardiac resynchronization therapy-defibrillator or and implantable cardioverter defibrillator, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (brain natriuretic peptide [BNP] of ≥150 pg/mL or N-terminal pro-BNP [NT-proBNP] of ≥600 pg/mL). This phase included the development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety.. The mean age of participants was 67 years, 68% were men, 81% were White, and 61% had a HF hospitalization in prior 12 months. During follow-up, there were 585 alert cases with an average of 1.76 alert cases per patient-year. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five serious adverse events (0.015 per patient-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (P < .001).. HeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies.. ClinicalTrials.gov (NCT03237858).

Topics: Aged; Algorithms; Cardiac Resynchronization Therapy; Defibrillators, Implantable; Female; Heart Failure; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume

Hypertension is a vital risk factor for heart failure, while cardiac rehabilita-tion can effectively improve cardiac function of heart failure patients. This study aimed to determine the impact of cardiac rehabilitation on microRNA-423-5p in hypertensive patients with heart failure with a moderately reduced ejection fraction.. Sixty hypertensive patients with heart failure with a moderately reduced ejec-tion fraction were randomly divided into cardiac rehabilitation group and positive control group with 30 cases per group, while 30 hypertensive patients without heart failure were recruited as negative control group. The cardiac rehabilitation group and positive control group were treated with 1-month cardiac rehabilitation combined with the routine treat-ment and routine treatment only, respectively. The New York Heart Association classi-fication, 6-minute walking test, and color Doppler echocardiography were adopted to detect cardiac function. Meanwhile, the expression of microRNA-423-5p and N-terminal pro-B-type natriuretic peptide was determined via Real-Time Fluorescence Quantitative PCR and electrochemiluminescence immunoassay. The diagnostic potential of microR- 423-5p and N-terminal pro-B-type natriuretic peptide was assessed by ROC curve analy- sis and multivariate linear regression model.. Patients in cardiac rehabilitation group displayed significantly lower expression of microR-423-5p and better results of New York Heart Association classification, 6-min-ute walking test, and color Doppler echocardiography than those in positive controlgroup (P < .05). ROC analysis showed that microR-423-5p (AUC = 0.785; 95% CI: 0.686- 0.865; sensitivity = 73.33%; specificity = 73.33%) had better specificity and accuracy thanN-terminal pro-B-type natriuretic peptide (AUC=0.721; 95% CI: 0.617-0.811; sensitiv- ity = 81.67%; specificity = 63.33%).. MicroR-423-5p was implicated in left ventricular hypertrophy and might be a potential biomarker for assessing the therapeutic effect of cardiac rehabilitation on hypertensive patients with heart failure with a moderately reduced ejection fraction.

Topics: Biomarkers; Cardiac Rehabilitation; Circulating MicroRNA; Heart Failure; Humans; Hypertension; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status.. Patients in the EVALUATE-HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12-week open-label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 weeks of treatment, NT-proBNP, sST2 and cTnT decreased by median (Q1, Q3) -31% (-55%, +6%), -6% (-19%, +8%) and - 3% (-13%, +8%), respectively (all p < 0.001). Decreases in NT-proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in left ventricular mass, but not with changes in left ventricular function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There was no effect modification from treatment on the associations investigated (p for interaction >0.05) CONCLUSION: In HFrEF, serial changes in NT-proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes in NT-proBNP, cTnT and sST2.. ClinicalTrials.gov Identifier: NCT02874794.

Topics: Aged; Aminobutyrates; Biomarkers; Biphenyl Compounds; Female; Health Status; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Troponin T; Valsartan

Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.. The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.. Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P< .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.. In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.

Topics: Atrial Fibrillation; Biomarkers; Cystatin C; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Interleukin-6; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Troponin T

Patients with heart failure (HF) and coronary artery disease (CAD) have a high risk for cardiovascular (CV) events including HF hospitalization, stroke, myocardial infarction (MI) and sudden cardiac death (SCD). The present study evaluated associations of proteomic biomarkers with CV outcome in patients with CAD and HF with reduced ejection fraction (HFrEF), shortly after a worsening HF episode. We performed a case-control study within the COMMANDER HF international, double-blind, randomized placebo-controlled trial investigating the effects of the factor-Xa inhibitor rivaroxaban. Patients with the following first clinical events: HF hospitalization, SCD and the composite of MI or stroke were matched with corresponding controls for age, sex and study drug. Plasma concentrations of 276 proteins with known associations with CV and cardiometabolic mechanisms were analyzed. Results were corrected for multiple testing using false discovery rate (FDR). In 485 cases and 455 controls, 49 proteins were significantly associated with clinical events of which seven had an adjusted FDR < 0.001 (NT-proBNP, BNP, T-cell immunoglobulin and mucin domain containing 4 (TIMD4), fibroblast growth factor 23 (FGF-23), growth differentiation factor-15 (GDF-15), pulmonary surfactant-associated protein D (PSP-D) and Spondin-1 (SPON1)). No significant interactions were identified between the type of clinical event (MI/stroke, SCD or HFH) and specific biomarkers (all interaction FDR > 0.20). When adding the biomarkers significantly associated with the above outcome to a clinical model (including NT-proBNP), the C-index increase was 0.057 (0.033-0.082), p < 0.0001 and the net reclassification index was 54.9 (42.5 to 67.3), p < 0.0001. In patients with HFrEF and CAD following HF hospitalization, we found that NT-proBNP, BNP, TIMD4, FGF-23, GDF-15, PSP-D and SPON1, biomarkers broadly associated with inflammation and remodeling mechanistic pathways, were strong but indiscriminate predictors of a variety of individual CV events.

Topics: Atrial Remodeling; Biomarkers; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Proteomics; Stroke; Stroke Volume; Ventricular Dysfunction, Left

To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF).. ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation.. ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.

Topics: Acetazolamide; Aged; Diuretics; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Ventricular Function, Left; Water-Electrolyte Imbalance

The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization.. The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk.. Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations.. Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78).. In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532).

Topics: Atrasentan; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Endothelin Receptor Antagonists; Endothelins; Heart Failure; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Weight Gain

We investigated the effects of CD34. ClinicalTrials.gov NCT02923609.

Topics: Cell- and Tissue-Based Therapy; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prospective Studies; Stroke Volume

The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies.. This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%).. When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events.. ClinicalTrials.gov NCT02270840.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiac Resynchronization Therapy; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.. In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed.. A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.. The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

Topics: Acetazolamide; Acute Disease; Carbonic Anhydrase Inhibitors; Diuretics; Double-Blind Method; Heart Failure; Humans; Natriuretic Peptide, Brain; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Symptom Flare Up; Treatment Outcome; Ventricular Function, Left; Water-Electrolyte Imbalance

Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking.. In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups.. In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters.. NCT03087773.

Topics: Biomarkers; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used for diagnostic and prognostic evaluation in heart failure (HF). Previous clinical trials in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) have shown potential heterogeneity in the treatment response by baseline NT-proBNP levels.. The purpose of this study was to assess the treatment effect of dapagliflozin across baseline levels of NT-proBNP among patients with HFmrEF or HFpEF.. This was a post hoc analysis from DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure), a randomized, placebo-controlled trial of dapagliflozin in patients with HFmrEF or HFpEF. Elevated NT-proBNP was part of the inclusion criteria (≥300 ng/L for non-atrial fibrillation or flutter [AFF]; ≥600 ng/L for AFF). Baseline NT-proBNP was categorized in quartiles and additionally analyzed continuously. The primary composite outcome was cardiovascular death or worsening HF events.. Among the 6,262 included patients (mean: 71.7 years and 3,516 [56%] men), the median baseline concentration of NT-proBNP was 716 (Q1-Q3: 469-1,280) ng/L and 1,399 (Q1-Q3: 962-2,212) ng/L for non-AFF and AFF, respectively. Higher NT-proBNP levels were linearly associated with a greater risk of the primary outcome (adjusted HR for log. Dapagliflozin is safe and improves outcomes irrespective of baseline NT-proBNP concentrations in HFmrEF or HFpEF, with the greatest absolute benefit likely seen in patients with higher NT-proBNP concentrations. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Topics: Atrial Fibrillation; Biomarkers; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Ventricular Dysfunction, Left

The valsartan-sacubitril therapy improved the outcomes of patients with acute decompensated heart failure (ADHF) of a reduced ejection fraction (HFrEF). In ADHF patients with preserved ejection fraction (HFpEF), it is not yet clear whether the same treatment regimen may be safely used to treat ADHF.. For this study, HFpEF patients hospitalized due to ADHF were enrolled. Following hemodynamic stabilization, patients were randomized into two groups that were treated with enalapril or sacubitril-valsartan. In this trial, the primary efficacy outcomes were changes in echocardiographic parameters and NT-proBNP levels from baseline to 8 weeks treatment.. ARNI treatment resulted in a significant decrease in NT-proBNP levels and an increase in LVEF in patients with HFpEF. However, HFpEF patients that underwent ARNI treatment achieved better outcomes than did patients that underwent ACEI treatment.. Sacubitril-valsartan treatment, which lowered NT-proBNP levels and improved cardiac function, was more effective in HFpEF patients with acute decompensated heart failure than enalapril.

Topics: Aminobutyrates; Angiotensins; Biphenyl Compounds; Echocardiography; Enalapril; Heart Failure; Humans; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Stroke Volume; Tetrazoles; Valsartan

Left bundle branch pacing (LBBP) is the most rapidly growing conduction system pacing technique that is capable of correcting intrinsic left bundle branch block (LBBB). As such, it is potentially an optimal alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP).. The authors sought to compare the efficacy of LBBP-CRT with BiVP-CRT in patients with heart failure and reduced left ventricular ejection fraction (LVEF).. This is a prospective, randomized trial of patients with nonischemic cardiomyopathy and LBBB with 6-month preplanned follow-up. Crossovers were allowed if LBBP or BiVP were unsuccessful. The primary endpoint was the difference in LVEF improvement between 2 groups. The secondary endpoints included changes in echocardiographic measurements, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, 6-minute walk distance, QRS duration, and CRT response.. The study included 40 consecutive patients (20 males, mean age 63.7 years, LVEF 29.7% ± 5.6%). Crossovers occurred in 10% of LBBP-CRT and 20% of BiVP-CRT. All patients completed follow-up. Intention-to-treat analysis showed significantly higher LVEF improvement at 6 months after LBBP-CRT than BiVP-CRT (mean difference: 5.6%; 95% CI: 0.3-10.9; P = 0.039). LBBP-CRT also appeared to have greater reductions in left ventricular end-systolic volume (-24.97 mL; 95% CI: -49.58 to -0.36 mL) and NT-proBNP (-1,071.80 pg/mL; 95% CI: -2,099.40 to -44.20 pg/mL), and comparable changes in New York Heart Association functional class, 6-minute walk distance, QRS duration, and rates of CRT response compared with BiVP-CRT.. LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in heart failure patients with nonischemic cardiomyopathy and LBBB. (Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy [LBBP-RESYNC]; NCT04110431).

Topics: Arrhythmias, Cardiac; Bundle-Branch Block; Cardiac Resynchronization Therapy; Electrocardiography; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.. The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.. A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined.. Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63).. Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH.

Topics: Antihypertensive Agents; Biomarkers; Blood Pressure; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Natriuretic Peptide, Brain; Risk Factors; Troponin T

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

To evaluate the effectiveness and safety of intravenous nicorandil application in patients with acute heart failure (AHF) with low baseline blood pressure (systolic blood pressure <110 mmHg).. This prospective, controlled, single-centre study randomised 147 patients with AHF with low baseline blood pressure (including both emergent admission and newly developed low blood pressure while in hospital) to one of the following two groups: (1) control group (conventional diuretics, positive inotropic agents, and related therapy according to the guidelines); and (2) intervention group (intravenous [IV] nicorandil application plus routine care). Dyspnoea severity, the ratio of E to e' (E/e'), the incidence of side effects and adverse events, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, left ventricular ejection fraction (LVEF; left ventricular systolic function) before discharge, average length of hospitalisation, LVEF and soluble suppression of tumorigenicity-2 (sST2) at 3 months after discharge, incidence of major adverse cardiac and cerebrovascular events (MACCE) and readmission rate within 3 months were recorded and compared between the two groups.. Compared to the control group, nicorandil relieved dyspnoea effectively and improved E/e' significantly; the level of NT-proBNP was lower, LVEF was higher before discharge, and average length of hospital stay was shorter in the intervention group. After 3 months, the LVEF was higher, sST2 was lower, and the readmission rate was lower in the intervention group; there was no statistically significant difference in MACCE.. Patients with AHF with low baseline blood pressure could benefit from IV nicorandil application in the urgent phase, but the long-term profits remained to be confirmed.

Topics: Biomarkers; Blood Pressure; Heart Failure; Humans; Hypotension; Natriuretic Peptide, Brain; Nicorandil; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Function, Left

Home telemonitoring in heart failure (HF) patients may reduce workload of HF nurses by reducing face-to-face contacts. The aim of this study is to assess whether telemonitoring as a substitution could have negative effects as expressed by less reduction in circulating natriuretic peptide levels between baseline and one-year of follow up compared to usual care.. A post-hoc analysis of the e-Vita HF trial, a three-arm parallel randomized trial conducted in stable HF patients. Patients were randomized into three arms: (i) usual HF outpatient care, (ii) usual care combined with the use of the website heartfailurematters.org, and (iii) telemonitoring (e-Vita HF platform) instead of face-to-face consultations. Mixed linear model analyses were applied to assess differences in the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels between the three arms over a year.. A total of 223 participants could be included (mean age 67.1 ± 10.1 years, 27% women, New York Heart Association class I-IV; 39%, 38%, 14%, and 9%). The mean left ventricular ejection fraction was 35 ± 10%. The median of routine face-to-face contacts over a year was 1.0 lower (2.0 vs. 3.0) in the third arm compared with usual care. Median NT-proBNP levels did not significantly differ between the three arms.. In stable and optimally treated HF patients, telemonitoring causing a reduction of routine face-to-face contacts seems not to negatively affect hemodynamic status as measured by NT-proBNP levels over time.

Topics: Aged; Biomarkers; Disease Management; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Stroke Volume; Telemedicine; 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

Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline.. Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function.. The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04).. In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

Topics: Aged; Biomarkers; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Diastole; Female; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

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

Ivabradine, which reduces heart rate (HR) without affecting sympathetic nerve activity, improves mortality and morbidity in patients with systolic dysfunction. However, its impact on up-titrating a concomitant beta-blocker dose in such a cohort, via increasing cardiac output and blood pressure and improving tolerability to beta-blockers, remains unknown. In this single-center, prospective, randomized control trial, patients with systolic dysfunction, defined as left ventricular ejection fraction < 50%, sinus rhythm, heart rate > 75 bpm, systolic blood pressure between 90 and 110 mmHg, and New York Heart Association functional class III or IV, who are refractory to up-titration of a beta-blocker due to symptomatic hypotension, dizziness, or worsening heart failure, were assigned to the 20 ivabradine arm or the 20 conventional therapy arm and followed-up for 6 months. The primary outcome is the daily dose of beta-blocker at 6-months follow-up. The secondary outcomes are echocardiographic parameters including overlap between E-wave and A-wave in transmitral diastolic filling flow, plasma B-type natriuretic peptide level, 6-minute walk distance, and heart failure readmission rate. By conducting this study, we hope to demonstrate the clinical benefit of ivabradine therapy in up-titrating beta-blockers and improving clinical outcomes in patients with systolic dysfunction.

Topics: Adrenergic beta-Antagonists; Biomarkers; Cardiovascular Agents; Echocardiography; Heart Failure; Humans; Ivabradine; Natriuretic Peptide, Brain; Patient Readmission; Prospective Studies; Systole; Walk Test

There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%).. To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%.. A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019).. Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor.. Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks.. Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%).. Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients.. ClinicalTrials.gov Identifier: NCT03066804.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Double-Blind Method; Drug Combinations; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Stroke Volume; Valsartan; Walk Test

To evaluate the effects of early administration of Sacubitril/Valsartan (Sac/Val) in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention (pPCI).. This prospective, controlled, single-center study randomized 186 ST-segment elevation myocardial infarction patients to one of the following two groups: Sac/Val group: early administration of Sac/Val within 24 hours after pPCI; control group: conventional angiotensin-converting enzyme inhibitors (ACEI) application. The creatine Kinase (CK) peak after the surgery, the incidence of acute heart failure during hospitalization, level of NT-proBNP and left ventricular ejection fraction (LVEF) measured by ultrasound before discharge and soluble suppression of tumorigenicity2 (sST2), LVEF, infarct size determined by single photon emission computed tomography (SPECT), readmission rate within 6 months were recorded and compared between two groups.. Compared to the control group, Sac/Val could decrease the CK peak and the incidence of acute heart failure after pPCI; the level of NT-proBNP was lower and LVEF was higher before discharge in the Sac/Val group. After 6 months, the patients who had taken Sac/Val had a higher LVEF, a smaller infarct size determined by SPECT, lower sST2 and readmission rate.. Patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention could benefit from early administration of Sacubitril/Valsartan, the effect was superior to conventional ACEI.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anterior Wall Myocardial Infarction; Biphenyl Compounds; Drug Combinations; Drug Monitoring; Early Medical Intervention; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Stroke Volume; Treatment Outcome; Valsartan

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure.. The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care.. The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

Topics: Acute Disease; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Disease Progression; Glucosides; Heart Failure; Hospital Mortality; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Hypotension; Hypovolemia; Insulin; Natriuresis; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Weight Loss

Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405).. Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed a median 23.3% NT-proBNP reduction, vs. a 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and encouraging positive trends for relevant cardiac fibrosis biomarkers.. This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. Although this study is limited by the small patient numbers, the indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.

Topics: Double-Blind Method; Heart Failure; Humans; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE-TIMI 58. We hypothesized that baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT-proBNP and hsTnT levels.. This was a pre-specified biomarker study from DECLARE-TIMI 58, a randomized, double-blind, placebo-controlled CV outcomes trial of dapagliflozin. Baseline NT-proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT-proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35-165] and 10.2 pg/mL (IQR 6.9-15.5), respectively. Patients with higher NT-proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT-proBNP: 4-year Kaplan-Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P-trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT-proBNP (P-interaction 0.72) or hsTnT quartiles (P-interaction 0.93). Given their higher baseline risk, patients with NT-proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT-proBNP 1.9% vs. 0%, P-interaction 0.010; hsTnT 1.8% vs. 0.1%, P-interaction 0.026).. Patients with type 2 diabetes mellitus and higher NT-proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT-proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Female; Glucose; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters

There are insufficient direct comparative studies addressing the impact of the type of statin on their respective efficacy in heart failure (HF). The aim of the current study was to compare the effects of lipophilic (atorvastatin) vs hydrophilic (rosuvastatin) on left ventricular function, inflammatory and fibrosis biomarkers in patients with chronic HF.. This was a prospective, randomized, comparative, parallel study. A total of 85 patients with chronic HF optimized on guideline directed therapy were randomized to receive either atorvastatin 40 mg (n = 42) or rosuvastatin 20 mg (n = 43) for 6 months. Baseline and follow-up assessment included 2D echocardiography, measurement of N-terminal pro-brain natriuretic peptide, interleukin-6 and soluble suppression of tumorigenicity 2 (sST2) levels, liver enzymes and lipid profile.. The increase in left ventricular ejection fraction was significantly higher in the atorvastatin group compared to the rosuvastatin group (6.5% [3-11] vs 4% [2-5], P = .006). The reduction in left ventricular end diastolic and end systolic volume was comparable between the 2 groups. The decrease in sST2 levels in pg/mL was significantly higher in the atorvastatin compared to the rosuvastatin group (-255 [-383 to -109.8 vs - 151 [-216 to -69], P = .003). There was a significant reduction in N-terminal pro-brain natriuretic peptide and interleukin-6 levels in both groups, yet the reduction was comparable in both groups.. The study results suggest that lipophilic atorvastatin is superior to hydrophilic rosuvastatin in increasing left ventricular ejection fraction and reducing fibrosis marker sST2 in HF patients. Trial registration ID: NCT03255044, registered on 21 August 2017.

Topics: Biomarkers; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Ventricular Function, Left

The inflammatory cytokine IL-6 has been previously implicated in the pathophysiology of acute decompensated heart failure (HF). Prior observations in acute HF patients have suggested that IL-6 may be associated with outcomes and modulated by nesiritide. We aimed to evaluate the associations between serial IL-6 measurements, mortality and rehospitalization in acute HF.. We analyzed the associations between IL-6 in acute HF, readmission, and mortality (30 and 180 days) using a cohort of 883 hospitalized patients from the ASCEND-HF trial (nesiritide vs placebo). Plasma IL-6 was measured at randomization (baseline), 48-72 hours, and 30 days. The median IL-6 was highest at baseline (14.1 pg/mL) and decreased at subsequent time points (7.6 pg/mL at 30 days). In a univariable Cox regression analysis, the baseline IL-6 was associated with 30- and 180-day mortality (hazard ratio per log 1.74, 95% confidence interval 1.09-2.78, P = .021; hazard ratio 3.23, confidence interval 1.18-8.86, P = .022, respectively). However, there was no association after multivariable adjustment. IL-6 at 48-72 hours was found to be independently associated with 30-day mortality (hazard ratio 8.2, confidence interval 1.2-57.5, P= .03), but not 180-day mortality in multivariable analysis that included the ASCEND-HF risk model and amino terminal pro-B-type natriuretic peptide as covariates. In comparison with placebo, nesiritide therapy was not associated with differences in serial IL-6 levels.. Although elevated IL-6 levels were associated with higher all-cause mortality in acute HF, no independent association with this outcome was identified at baseline or 30-day measurements. In contrast with prior reports, we did not observe any impact of nesiritide over placebo on serial IL-6 levels.

Topics: Acute Disease; Heart Failure; Humans; Interleukin-6; Natriuretic Agents; Natriuretic Peptide, Brain; Proportional Hazards Models

This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.. In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.. Baseline, 1-month, and 9-month (or last visit) plasma samples of HOMAGE participants were measured for protein biomarkers (n = 276) by using Olink Proseek-Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden). The effect of spironolactone on biomarkers was assessed by analysis of covariance and explored by knowledge-based network analysis.. A total of 527 participants were enrolled; 265 were randomized to spironolactone (25 to 50 mg/day) and 262 to standard care ("control"). The median (interquartile range) age was 73 years (69 to 79 years), and 26% were female. Spironolactone reduced biomarkers of collagen metabolism (e.g., COL1A1, MMP-2); brain natriuretic peptide; and biomarkers related to metabolic processes (e.g., PAPPA), inflammation, and thrombosis (e.g., IL17A, VEGF, and urokinase). Spironolactone increased biomarkers that reflect the blockade of the mineralocorticoid receptor (e.g., renin) and increased the levels of adipokines involved in the anti-inflammatory response (e.g., RARRES2) and biomarkers of hemostasis maintenance (e.g., tPA, UPAR), myelosuppressive activity (e.g., CCL16), insulin suppression (e.g., RETN), and inflammatory regulation (e.g., IL-12B).. Proteomic analyses suggest that spironolactone exerts pleiotropic effects including reduction in fibrosis, inflammation, thrombosis, congestion, and vascular function improvement, all of which may mediate cardiovascular protective effects, potentially slowing progression toward heart failure. (HOMAGE [Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure]; NCT02556450).

Topics: Aged; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Proteomics; Spironolactone

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Carvedilol; Child; Cross-Over Studies; Double-Blind Method; Exercise; Exercise Test; Female; Fontan Procedure; Heart Failure; Heart Rate; Humans; Male; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Treatment Outcome; Young Adult

Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure.. The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula.. In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Blood Glucose; COVID-19; Creatinine; Diabetes Mellitus, Type 2; Early Termination of Clinical Trials; Female; Glucosides; Heart Failure; Hospitalization; Humans; Japan; Kidney; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Biomarkers; Body Mass Index; Diuretics; Dose-Response Relationship, Drug; Female; Heart Failure; Hospitalization; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Precursors; Stroke Volume

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

This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, β receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.

Topics: Acute Disease; Adrenergic beta-Antagonists; Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arterial Pressure; Biomarkers; Biphenyl Compounds; Drug Combinations; Drug Therapy, Combination; Female; Heart Failure; Hormone Antagonists; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Pulmonary Artery; Stroke Volume; Tetrazoles; Treatment Outcome; Troponin T; Valsartan

Topics: Aged; Atherosclerosis; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Risk Factors; Secondary Prevention; Thrombolytic Therapy; Thrombosis; Troponin I

Myocardial injury of ST-segment elevation myocardial infarction (STEMI) initiates an intense inflammatory response that contributes to further damage and is a predictor of increased risk of death or heart failure (HF). Interleukin-1 (IL-1) is a key mediator of local and systemic inflammatory response to myocardial damage. We postulate that the use of the drug RPH-104, which selectively binds and inactivates both α and β isoforms of IL-1 will lead to a decrease in the severity of the inflammatory response which will be reflected by decrease in the concentration of hsCRP, as well as the rate of fatal outcomes, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP) and changes in structural and functional echocardiographic parameters.. This is a double blind, randomized, placebo-controlled study in which 102 patients with STEMI will receive a single administration of RPH-104 80 mg, RPH-104 160 mg or placebo (1:1:1). The primary endpoint will be hsCRP area under curve (AUC) from day 1 until day 14. Secondary endpoints will include hsCRP AUC from day 1 until day 28, rate of fatal outcomes, hospitalizations due to HF and other cardiac and non-cardiac reasons during 12-month follow-up period, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP, NT-pro-BNP), changes in structural and functional echocardiographic parameters during 12-month follow-up period compared to baseline. The study started in October 2020 and is anticipated to end in 2Q 2022.. ClinicalTrials.gov, NCT04463251. Registered on July 9, 2020.

Topics: Biomarkers; C-Reactive Protein; Echocardiography; Heart Failure; Humans; Interleukin-1; Natriuretic Peptide, Brain; ST Elevation Myocardial Infarction

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a prognostic biomarker in heart failure (HF) with reduced ejection fraction. However, it is unclear whether there is a sex difference in NT-proBNP response and whether the therapeutic goal of NT-proBNP ≤1000 pg/mL has equivalent prognostic value in men and women with HF with reduced ejection fraction. Methods and Results In a secondary analysis of the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial we analyzed trends in NT-proBNP and goal attainment by sex. Differences in clinical characteristics, HF treatment, and time to all-cause death or HF hospitalization were compared. Landmark analysis at 3 months determined the prognostic value of early NT-proBNP goal achievement in men and women. Of the 286 (32%) women and 608 (68%) men in the GUIDE-IT trial, women were more likely to have a nonischemic cause and shorter duration of HF. Guideline-directed medical therapy was less intense over time in women. The absolute NT-proBNP values were consistently lower in women; however, the change in NT-proBNP and clinical outcomes were similar. After adjustment, women achieving the NT-proBNP goal had an 82% reduction in death or HF hospitalization compared with a 59% reduction in men. Conclusions Men and women with HF with reduced ejection fraction had a similar NT-proBNP response despite less intensive HF treatment among women. However, compared with men, the early NT-proBNP goal of ≤1000 pg/mL had greater prognostic value in women. Future efforts should be aimed at intensifying guideline-directed medical therapy in women, which may result in greater NT-proBNP reductions and improved outcomes in women with HF with reduced ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Canada; Cause of Death; Female; Follow-Up Studies; Guideline Adherence; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Sex Distribution; Sex Factors; Stroke Volume; United States

The aim of this study was to assess sex differences in the efficacy and safety of baroreflex activation therapy (BAT) in the BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial.. Patients were randomized 1:1 to receive guideline-directed medical therapy (GDMT) alone (control group) or BAT plus GDMT.. Pre-specified subgroup analyses including change from baseline to 6 months in 6-min walk distance (6MWD), quality of life (QoL) assessed using the Minnesota Living With Heart Failure Questionnaire (MLWHQ), New York Heart Association (NYHA) functional class, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were conducted in men versus women.. Fifty-three women and 211 men were evaluated. Women had similar baseline NT-proBNP levels, 6MWDs, and percentage of subjects with NYHA functional class III symptoms but poorer MLWHQ scores (mean 62 ± 22 vs. 50 ± 24; p = 0.01) compared with men. Women experienced significant improvement from baseline to 6 months with BAT plus GDMT relative to GDMT alone in MLWHQ score (-34 ± 27 vs. -9 ± 23, respectively; p < 0.01), 6MWD (44 ± 45 m vs. -32 ± 118 m; p < 0.01), and improvement in NYHA functional class (70% vs. 27%; p < 0.01), similar to the responses seen in men, with no significant difference in safety. Women receiving BAT plus GDMT had a significant decrease in NT-proBNP (-43% vs. 7% with GDMT alone; difference -48%; p < 0.01), while in men this decrease was -15% versus 2%, respectively (difference -17%; p = 0.08), with an interaction p value of 0.05.. Women in BeAT-HF had poorer baseline QoL than men but demonstrated similar improvements with BAT in 6MWD, QoL, and NYHA functional class. Women had a significant improvement in NT-proBNP, whereas men did not. (Baroreflex Activation Therapy for Heart Failure [BeAT-HF]; NCT02627196).

Topics: Baroreflex; Electric Stimulation Therapy; Female; Heart Failure; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain; Patient-Centered Care; Peptide Fragments; Quality of Life; Stroke Volume

It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score (PRS) for survival in patients with HFrEF (HFrEF-PRS).. Patients meeting Framingham criteria for HF with EF<50% were enrolled (N=1017) and plasma underwent SOMAscan profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation cohorts. The HFrEF-PRS was derived using Cox regression of all-cause mortality adjusted for clinical score and NT-proBNP (N-terminal pro-B-type natriuretic peptide), then was tested in the validation cohort. Risk stratification improvement was evaluated by C statistic, integrated discrimination index, continuous net reclassification index, and median improvement in risk score for 1-year and 3-year mortality.. Participants' mean age was 68 years, 48% identified as Black, 35% were female, and 296 deaths occurred. In derivation (n=681), 128 proteins associated with mortality, 8 comprising the optimized HFrEF-PRS. In validation (n=336) the HFrEF-PRS associated with mortality (hazard ratio, 2.27 [95% CI, 1.84-2.82],. A plasma multiprotein score improved risk stratification in patients with HFrEF and identified novel candidates.

Topics: Aged; Biomarkers; Disease-Free Survival; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Proteomics; Stroke Volume; Survival Rate

Natriuretic peptides have broad indications during heart failure and the detection of left ventricular dysfunction in high-risk patients. They can also be used for the diagnosis/management of other cardiac diseases. However, very little is known regarding their use in routine practice.. We examined all biological tests performed from February 2010 to August 2015 in two districts from the French Brittany, covering 13,653 km. Among a very large cohort, we observed that natriuretic peptides remain largely undermeasured. NT-proBNP is mostly measured in elderly patients, and its interpretation may be hazardous in up to 16% of all individuals because no measurement of creatinine was associated to NT-proBNP.

Topics: Adult; Age Factors; Aged; Big Data; Biomarkers; Creatinine; Data Analysis; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Ventricular Dysfunction, Left

Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies.. This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment.. Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832).. In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated.

Topics: Creatinine; Diuretics; Drug Monitoring; Female; Furosemide; Heart Failure; Hospitalization; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Outcome and Process Assessment, Health Care; Patient Readmission; Peptide Fragments; Time-to-Treatment; United States

To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD).. One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included.. Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated.. Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak.. Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

Topics: Animals; Biomarkers; Death; Dog Diseases; Dogs; Echocardiography; Heart Failure; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Topics: Aged; Cardiomyopathy, Dilated; Feasibility Studies; Female; Heart Failure; Histones; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Recovery of Function; Regression Analysis; Stem Cell Transplantation; Stroke Volume; Transplantation, Autologous; Treatment Outcome; Ventricular Function, Left; Walk Test

To investigate the effects of hydralazine combined with nitrate on serum levels of Adropin and brain natriuretic peptide (BNP), left ventricular remodeling and prognosis in patients with chronic heart failure (CHF). 126 CHF patients were divided into control group (n=13, sodium nitroprusside) and combined treatment group (n=63, sodium nitroprusside ± hydralazine). Serum Adropin and BNP levels and left ventricular mass index (LVMI) of patients before treatment and 10 days after treatment were recorded, so did patient's end-point events. It was found that compared with those before treatment, the serum levels of Adropin, BNP, and LVMI in combined group and control group after 10 days of treatment were lower (P<0.05). The end-point event rate in the combined group was 19.05% (12/63). The serum levels of Adropin, BNP, and LVMI in the combined group with end-point events were higher than those of patients without end-point events (P<0.05). Spearman correlation analysis showed that serum levels of Adropin and BNP were positively correlated with LVMI and the end-point events rate (P<0.05). To sum up, hydralazine combined with sodium nitroprusside treatment can effectively reduce serum Adropin and BNP levels, and the risk of left ventricular remodeling and poor prognosis in patients with CHF.

Topics: Aged; Aged, 80 and over; Female; Heart Failure; Humans; Hydralazine; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Nitroprusside; Prognosis; Vasodilator Agents; Ventricular Remodeling

Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction. We investigated whether plasma levels of MR-proADM and NT-proBNP are associated with blood pressure fluctuations during PPGL resection.. Study subjects participated in PRESCRIPT, a randomized controlled trial in patients undergoing PPGL resection. MR-proADM and NT-proBNP were determined in a single plasma sample drawn before surgery. Multivariable linear and logistic regression analyses were used to explore associations between these biomarkers and blood pressure fluctuations, use of vasoconstrictive agents during surgery as well as the occurrence of perioperative cardiovascular events.. A total of 126 PPGL patients were included. Median plasma concentrations of MR-proADM and NT-proBNP were 0.51 (0.41-0.63) nmol/L and 68.7 (27.9-150.4) ng/L, respectively. Neither MR-proADM nor NT-proBNP were associated with blood pressure fluctuations. There was a positive correlation between MR-proADM concentration and the cumulative dose of vasoconstrictive agents (03B2 0.44, P =0.001). Both MR-proADM and NT-proBNP were significantly associated with perioperative cardiovascular events (OR: 5.46, P =0.013 and OR: 1.54, P =0.017, respectively).. plasma MR-proADM or NT-proBNP should not be considered as biomarkers for the presurgical risk assessment of blood pressure fluctuations during PPGL resection. Future studies are needed to explore the potential influence of these biomarkers on the intraoperative requirement of vasoconstrictive agents and the perioperative cardiovascular risk.

Topics: Adrenal Gland Neoplasms; Adrenergic Antagonists; Adrenomedullin; Adult; Aged; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cross-Sectional Studies; Female; Follow-Up Studies; Heart Failure; Humans; Intraoperative Complications; Male; Middle Aged; Natriuretic Peptide, Brain; Pheochromocytoma; Prognosis; Risk Assessment; Treatment Outcome

The identification of high-risk heart failure (HF) patients makes it possible to intensify their treatment. Our aim was to determine the prognostic value of a newly developed, high-sensitivity troponin I assay (Atellica®, Siemens Healthcare Diagnostics) for patients with HF with reduced ejection fraction (HFrEF; LVEF < 40%) and HF with mid-range EF (HFmrEF) (LVEF 40%-49%).. A total of 520 patients with HFrEF and HFmrEF were enrolled in this study. Two-year all-cause mortality, heart transplantation, and/or left ventricular assist device implantation were defined as the primary endpoints (EP). A logistic regression analysis was used for the identification of predictors and development of multivariable models. The EP occurred in 14% of the patients, and these patients had higher NT-proBNP (1,950 vs. 518 ng/l; p < 0.001) and hs-cTnI (34 vs. 17 ng/l, p < 0.001) levels. C-statistics demonstrated that the optimal cut-off value for the hs-cTnI level was 17 ng/l (AUC 0.658, p < 0.001). Described by the AUC, the discriminatory power of the multivariable model (NYHA > II, NT-proBNP, hs-cTnI and urea) was 0.823 (p < 0.001). Including heart failure hospitalization as the component of the combined secondary endpoint leads to a diminished predictive power of increased hs-cTnI.. hs-cTnI levels ≥ 17 ng/l represent an independent increased risk of an adverse prognosis for patients with HFrEF and HFmrEF. Determining a patient's hs-cTnI level adds prognostic value to NT-proBNP and clinical parameters.

Topics: Aged; Aged, 80 and over; Disease-Free Survival; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Male; Middle Aged; Models, Cardiovascular; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Survival Rate; Troponin I

The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozin according to age, given potential concerns about the efficacy and safety of therapies in the elderly.. Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure <95 mm Hg and estimated glomerular filtration rate <30 mL·min. A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were <55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4-17.9), 15.7 (95% CI, 13.2-18.7), 15.1 (95% CI, 13.1-17.5), and 18.0 (95% CI, 15.2-21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60-1.28), 0.71 (95% CI, 0.55-0.93), 0.76 (95% CI, 0.61-0.95), and 0.68 (95% CI, 0.53-0.88;. Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03036124.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Glucosides; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Placebo Effect; Proportional Hazards Models; Survival Analysis; Treatment Outcome; Ventricular Function, Left; Young Adult

In PIONEER-HF, among stabilized patients with acute decompensated heart failure (ADHF), the in-hospital initiation of sacubitril/valsartan was well tolerated and led to improved outcomes compared with enalapril. However, there are limited data comparing the strategies of in-hospital vs postdischarge initiation of sacubitril/valsartan.. To describe changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients recently hospitalized for ADHF and switching from taking enalapril to taking sacubitril/valsartan after discharge and compare clinical outcomes for patients randomized to receive in-hospital initiation of sacubitril/valsartan vs in-hospital initiation of enalapril who later switched to taking sacubitril/valsartan during an open-label extension phase.. Sacubitril/valsartan titrated to 97/103 mg twice daily.. The PIONEER-HF trial was a multicenter, randomized, double-blind, active-controlled trial conducted at 129 US sites between May 2016 and May 2018 that compared the in-hospital initiation of sacubitril/valsartan vs enalapril (titrated to target dose, 10 mg twice daily) for 8 weeks among patients admitted for ADHF with reduced ejection fraction and hemodynamic stability. All patients were to continue in a 4-week, open-label study of sacubitril/valsartan; of 881 patients enrolled in PIONEER-HF, 832 (94%) continued in the open-label study.. Changes in NT-proBNP levels from week 8 to 12 as well as the exploratory composite of heart failure rehospitalization or cardiovascular death from randomization through week 12.. Of 881 participants, 226 (27.7%) were women, 487 (58.5%) were white, 297 (35.7%) were black, 15 (1.8%) were Asian, and 73 (8.8%) were of Hispanic ethnicity; the mean (SD) age was 61 (14) years. For patients who continued to take sacubitril/valsartan, NT-proBNP levels declined -17.2% (95% CI, -3.2 to -29.1) from week 8 to 12. The NT-proBNP levels declined to a greater extent for those switching from taking enalapril to sacubitril/valsartan after the week 8 visit (-37.4%; 95% CI, -28.1 to -45.6; P < .001; comparing changes in 2 groups). Over the entire 12 weeks of follow-up, patients that began taking sacubitril/valsartan in the hospital had a lower hazard for the composite outcome compared with patients that initiated enalapril in the hospital and then had a delayed initiation of sacubitril/valsartan 8 weeks later (hazard ratio, 0.69; 95% CI 0.49-0.97).. Switching patients' treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF.. ClinicalTrials.gov identifier: NCT02554890.

Topics: Acute Disease; Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Drug Combinations; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Patient Discharge; Peptide Fragments; Tetrazoles; Valsartan

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

Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI.. Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints.. The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Double-Blind Method; Echocardiography; Glucosides; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Ketone Bodies; Length of Stay; Mortality; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Proteins; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Galectin 3; Galectins; Growth Differentiation Factor 15; Heart Disease Risk Factors; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Piperidines; Prognosis; Risk Assessment; Troponin I; Uracil

Inhibition of sodium-glucose co-transporter 2 (SGLT2) reduces the risk of death and heart failure (HF) admissions in patients with chronic HF. However, safety and clinical efficacy of SGLT2 inhibitors in patients with acute decompensated HF are unknown.. In this randomized, placebo-controlled, double-blind, parallel group, multicentre pilot study, we randomized 80 acute HF patients with and without diabetes to either empagliflozin 10 mg/day or placebo for 30 days. The primary outcomes were change in visual analogue scale (VAS) dyspnoea score, diuretic response (weight change per 40 mg furosemide), change in N-terminal pro brain natriuretic peptide (NT-proBNP), and length of stay. Secondary outcomes included safety and clinical endpoints. Mean age was 76 years, 33% were female, 47% had de novo HF and median NT-proBNP was 5236 pg/mL. No difference was observed in VAS dyspnoea score, diuretic response, length of stay, or change in NT-proBNP between empagliflozin and placebo. Empagliflozin reduced a combined endpoint of in-hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); P = 0.014]. Urinary output up until day 4 was significantly greater with empagliflozin vs. placebo [difference 3449 (95% confidence interval 578-6321) mL; P < 0.01]. Empagliflozin was safe, well tolerated, and had no adverse effects on blood pressure or renal function.. In patients with acute HF, treatment with empagliflozin had no effect on change in VAS dyspnoea, diuretic response, NT-proBNP, and length of hospital stay, but was safe, increased urinary output and reduced a combined endpoint of worsening HF, rehospitalization for HF or death at 60 days.

Topics: Aged; Benzhydryl Compounds; Double-Blind Method; Female; Glucosides; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Treatment Outcome

Asymptomatic patients with coronary artery disease (CAD), hypertension and/or type 2 diabetes mellitus (T2DM) are at greater risk of developing heart failure (HF). Fibrosis, leading to myocardial and vascular dysfunction, might be an important pathway of progression. The Heart OMics in AGing (HOMAGE) trial aims to investigate the effects of spironolactone on serum markers of collagen metabolism and on cardiovascular structure and function in people at risk of developing HF and potential interactions with a marker of fibrogenic activity, galectin-3.. The HOMAGE trial will provide insights on the effect of spironolactone on pathways that might drive progression to HF.. ClinicalTrials.gov NCT02556450.

Topics: Aged; Aging; Biomarkers; Diabetes Mellitus, Type 2; Female; Fibrosis; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Spironolactone; Stroke Volume; Ventricular Function, Left

Spironolactone has been demonstrated to reduce heart failure (HF) hospitalization in patients with HF with preserved ejection fraction in the Americas region of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We assessed effects of 12 months of treatment with spironolactone on biomarkers reflecting myocardial stress, myocardial injury, renal function, and systemic inflammation.. This TOPCAT biorepository substudy evaluated 247 patients (14% of the total 1767 patients in the Americas region) with symptomatic HF, ejection fraction ≥45%, and elevated natriuretic peptides or a prior HF hospitalization. Paired blood samples at baseline and after 12 months of treatment with spironolactone or placebo were available in 204 patients.. At baseline, the median (interquartile range) concentration of BNP (B-type natriuretic peptide) was 124 (69-197) ng/L, NT-proBNP (N-terminal-pro-B-type natriuretic peptide) 624 (307-1312) ng/L, hs-cTnI (high sensitivity cardiac troponin I) 6.3 (3.4-13.0) ng/L, hs-CRP (high sensitivity C-reactive protein) 2.8 (1.3-6.1) mg/L, uric acid 7.2 (5.8-8.7) mg/dL, and urine protein-creatinine ratio 0.11 (0.08-0.20) mg/mg. Compared with placebo-assigned participants at 12 months, those randomized to spironolactone experienced greater reductions from baseline in levels of NT-proBNP (. This TOPCAT biorepository substudy suggests potential effects on markers of cardiac wall stress or filling pressures during 12 months of treatment with spironolactone in patients with chronic HF with preserved ejection fraction.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Biomarkers; Cardiovascular System; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Spironolactone; Stroke Volume

In heart failure (HF) patients implanted with high-energy devices, worsening of HF can be diagnosed from intrathoracic impedance (ITI) before symptoms appear. Early therapeutic intervention can prevent HF worsening, but the optimal intervention remains unknown. This study aimed to examine which lifestyle modifications or medications can improve HF indicators in asymptomatic HF patients diagnosed from ITI.Methods and Results:This multicenter, prospective, randomized study included patients with high-energy devices, left ventricular ejection fraction <40%, or with a history of HF hospitalization. After the OptiVol alert was evoked by decreased ITI, patients underwent examinations. If they were diagnosed with HF, they were randomly assigned to 3 groups: lifestyle modification, diuretic, or nitrate. After 1 week, they underwent the same examinations. The primary endpoint was change in ITI and serum B-type natriuretic peptide (BNP). Totally, 57 patients were randomized. In all 3 groups, ITI was significantly increased post-intervention compared with pre-intervention. In the diuretic and nitrate groups, logBNP post-intervention was significantly lower than pre-intervention, but not in the lifestyle modification group.. Compared with lifestyle modifications, diuretic and nitrate therapy for 1 week may be more effective management of HF detected by decreased ITI. However, lifestyle modification may have the additional benefits of reducing the workload or cost.

Topics: Aged; Aged, 80 and over; Asymptomatic Diseases; Biomarkers; Diuretics; Female; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrates; Patient Admission; Peptide Fragments; Prospective Studies; Recovery of Function; Risk Factors; Risk Reduction Behavior; Time Factors; Treatment Outcome; Vasodilator Agents

Diuretic resistance portends a poor prognosis in acute heart failure, especially in advanced stages. Early identification of a poor response to diuretics may help to improve treatment and outcomes. Spot natriuresis (UNa. In patients with ACHF and dilutional hyponatremia, low natriuresis after furosemide is an early marker of poor diuretic response and correlates with higher NT-proBNP and higher incidence of worsening renal function at 72 h.

Topics: Administration, Intravenous; Aged; Biomarkers; Diuretics; Double-Blind Method; Drug Resistance; Female; Furosemide; Heart Failure; Humans; Hyponatremia; Kidney Function Tests; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium; Treatment Outcome

Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission.. STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate.. Soluble suppression of tumorigenicity 2-guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long-term outcome using sST2-guided therapy deserves further investigations.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prognosis; Prospective Studies

Guidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.. This study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.. Using 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.. Average age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.. Baseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Monitoring; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Neprilysin; Outcome Assessment, Health Care; Peptide Fragments; Sex Factors; Stroke Volume; Tetrazoles; Valsartan

The authors sought to evaluate the prognostic significance of baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP), whether NT-proBNP modified the treatment response to sacubitril/valsartan, and the treatment effect of sacubitril/valsartan on NT-proBNP overall and in key subgroups.. Sacubitril/valsartan reduces NT-proBNP in heart failure (HF) with both reduced and preserved ejection fraction (EF), but did not significantly reduce total HF hospitalizations and cardiovascular death compared with valsartan in patients with HF with preserved EF (HFpEF).. In the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial, 4,796 patients with HFpEF and elevated NT-proBNP were randomized to sacubitril/valsartan or valsartan. NT-proBNP was measured at screening in all patients and at 5 subsequent times in >2,700 patients: before, between, and after sequential valsartan and sacubitril/valsartan run-in periods, and 16 and 48 weeks post-randomization.. Median NT-proBNP was 911 pg/ml (interquartile range: 464 to 1,613 pg/ml) at screening. Screening NT-proBNP was strongly associated with the primary endpoint, total HF hospitalizations and cardiovascular death (rate ratio [RR]: 1.68 per log increase in NT-proBNP, 95% confidence interval [CI]: 1.53 to 1.85; p < 0.001). This relationship was stronger in patients with atrial fibrillation (adjusted RR: 2.33 [95% CI: 1.89 to 2.87] vs. 1.58 [95% CI: 1.42 to 1.75] in patients without atrial fibrillation; p interaction <0.001) and weaker in obese patients (adjusted RR: 1.50 [95% CI: 1.31 to 1.71] vs. 1.92 [95% CI: 1.70 to 2.17] in nonobese patients; p interaction <0.001). Screening NT-proBNP did not modify the treatment effect of sacubitril/valsartan compared with valsartan (p interaction = 0.96). Sacubitril/valsartan reduced NT-proBNP by 19% (95% CI: 14% to 23%; p < 0.001) compared with valsartan 16 weeks post-randomization, with similar reductions in men (20%) and women (18%), and in patients with left ventricular EF ≤57% (20%) and >57% (18%). Decreases in NT-proBNP predicted lower subsequent risk of the primary endpoint.. Baseline NT-proBNP predicted HF events but did not modify the sacubitril/valsartan treatment effect in patients with HFpEF. Sacubitril/valsartan reduced NT-proBNP consistently in men and women, and in patients with lower or higher EF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Double-Blind Method; Drug Combinations; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

The aim of this study was to assess the clinical characteristics of patients with heart failure and preserved ejection fraction (HFpEF) and atrial fibrillation (AF) and compare them with those of HFpEF patients without AF.. This study was a sub-group analysis of a multicenter, observational, and cross-sectional registry conducted in Turkey (ClinicalTrials.gov identifier: NCT03026114). Patients with HFpEF were divided into 2 groups: HFpEF with AF and HFpEF with sinus rhythm (SR), and the clinical characteristics of the groups were compared.. In a total of 819 HFpEF patients (median age: 67 years; 58% women), 313 (38.2%) had AF. Compared to the patients with SR, those with AF were older (70 years vs 66 years; p<0.001) and more symptomatic, with a higher rate of classification as New York Heart Association functional class III-IV, paroxysmal nocturnal dyspnea, orthopnea, palpitations, fatigue, pulmonary crepitations, and peripheral edema. The hospitalization rate for heart failure was higher (28.4% vs 12.6%; p<0.001) in patients with AF, and participants with AF had higher level of N-terminal pro-B-type natriuretic peptide (887 pg/mL vs 394.8 pg/mL; p<0.001) and higher left atrial volume index level. Patients without AF had a higher burden of diabetes mellitus, obstructive sleep apnea, and coronary artery disease. The prescription rate of nondihydropyridine calcium blockers, digoxin, loop diuretics, and anticoagulant drugs was higher in the AF group.. The results of this study revealed that in a large Turkish cohort with HFpEF, significant clinical differences were present between those with and without AF and. Further prospective studies are needed to clarify the prognostic implications of AF in this growing heart failure population in our country.

Topics: Aged; Atrial Fibrillation; Cardiac Electrophysiology; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Mellitus; Female; Heart Atria; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Registries; Sleep Apnea, Obstructive; Stroke Volume; Turkey; Ventricular Dysfunction, Left

Little is known about the impact of sodium glucose co-transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), in that patient population.. Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting-dose: 0.5 mg), were examined using the primary endpoint of non-inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two-sided 95% confidence interval (CI) for the group ratio of percentage change in NT-proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT-proBNP percentage change was 0.48 (95% CI, -0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non-inferiority margin. However, NT-proBNP levels did show a non-significant trend lower in the canagliflozin group [adjusted group difference; -74.7 pg/mL (95% CI, -159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [-58.3 (95% CI, -127.6 to 11.0, P = 0.098]).. This study did not meet the predefined primary endpoint of changes in NT-proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors.

Topics: Canagliflozin; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

This study sought to identify the role of annexin A1 (AnxA1) as a congestion marker in acute heart failure (AHF) and to identify its putative role in predicting clinical outcomes.. AnxA1 is a protein that inhibits inflammation following ischemia-reperfusion injury in cardiorenal tissues. Because AHF is a state of tissue hypoperfusion, we hypothesized that plasma AnxA1 levels are altered in AHF.. In the Renal Optimization Strategies Evaluation (ROSE) trial, patients hospitalized for AHF with kidney injury were randomized to receive dopamine, nesiritide, or placebo for 72 hours in addition to diuresis. In a subanalysis, plasma AnxA1 levels were measured at baseline and at 72 hours in 275 patients. Participants were divided into 3 tertiles based on their baseline AnxA1 levels.. The prevalence of peripheral edema 2+ increased with increasing AnxA1 levels (P < .007). Cystatin C, blood urea nitrogen, and kidney injury molecule-1 plasma levels were higher among participants in tertile 3 vs tertiles 1 or 2 (P< .05). Patients with a congestion score of 4 had a mean baseline AnxA1 level 8.63 units higher than those with a congestion score of 0 (P = .03). Patients in tertiles 2 and 3 were twice as likely to experience creatinine elevation as patients in tertile 1 (P = .03). Patients in tertiles 2 and 3 were at a higher risk of 60-day all-cause mortality or heart failure hospitalization and 180-day all-cause mortality (P < .05).. Among patients hospitalized for AHF with impaired kidney function, elevated AnxA1 levels are associated with worse congestion, higher risk for further creatinine elevation, and higher rates of 60-day morbidity or all-cause mortality and 180-day all-cause mortality.. clinicaltrials.gov Identifier: NCT01132846.

Topics: Acute Disease; Annexin A1; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Treatment Outcome

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

This study aimed to examine whether incorporation of a comprehensive set of measures of decongestion modifies the association of acute declines in kidney function with outcomes.. In-hospital acute declines in kidney function occur in approximately 20% to 30% of patients admitted with acute decompensated heart failure (ADHF) and may be associated with adverse outcomes.. Using data from EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan), we used multivariable Cox regression models to evaluate the association between in-hospital changes in estimated glomerular filtration rate (eGFR) with death and a composite outcome of cardiovascular death and hospitalization for heart failure. We evaluated eGFR declines within the context of changes in markers of volume overload including b-type natriuretic peptide (BNP), N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and weight, as well as changes in measures of hemoconcentration including hematocrit, albumin, and total protein.. Among 3,715 patients over a median follow-up of 9.9 months, every 30% decline in eGFR was associated with higher risk of both death (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.07 to 1.31) and the composite outcome (HR: 1.09; 95% CI: 1.01 to 1.18) in adjusted models. The acute decline in eGFR was no longer associated with higher risk of either outcome as long as there was evidence of decongestion, either by declines in BNP, NT-proBNP, or weight or by increases in hematocrit, albumin or total protein. Interaction testing between decline in eGFR and changes in hematocrit, albumin, and total protein was statistically significant (p interaction of <0.01 for death and p interaction of ≤0.01 for composite for all 3 biomarkers). Interaction between change in eGFR and changes in BNP (p interaction = 0.07 for death; p interaction = 0.08 for composite), NT-proBNP (p interaction = 0.15 for death; p interaction = 0.18 for composite) and weight (p interaction = 0.13 for death; p interaction = 0.19 for composite) did not meet statistical significance.. Overall, acute declines in eGFR are associated with adverse outcomes, with evidence of modification by changes in markers of decongestion, suggesting that they are no longer associated with adverse outcomes if these markers are concomitantly improving.

Topics: Acute Kidney Injury; Aged; Antidiuretic Hormone Receptor Antagonists; Biomarkers; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Tolvaptan

To assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on urinary sodium excretion as well as on circulating adrenomedullin and copeptin levels in patients with type 2 diabetes (T2D).. In the LIVE study, patients (n = 241) with left ventricular ejection fraction ≤45% were randomized to liraglutide 1.8 mg daily or placebo for 24 weeks, and 30% had a concomitant diagnosis of T2D. Plasma levels of N-terminal brain-natriuretic-peptide (NT-proBNP) (a predefined secondary endpoint), midregional pro-atrial-natriuretic-peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM) and copeptin were measured at baseline and after 24 weeks in this substudy. The potential effect modification of T2D was assessed.. In the eligible subgroup of 231 patients with available biomarkers (115 randomized to liraglutide and 116 to placebo), MR-proANP decreased by 12% (P = .002) and NT-proBNP by 9% (P = .009) during liraglutide treatment compared with placebo at week 24. Interaction with T2D for the treatment effect of change in MR-proANP and NT-proBNP levels was P = .003 and P = .03, respectively. Consequently, in patients with T2D, liraglutide decreased MR-proANP by 27% (P < .001) and NT-proBNP by 25% (P = .02) compared with placebo, whereas no change was observed in patients without T2D. There was no effect of liraglutide on MR-proADM (P = .10) or copeptin (P = .52).. Liraglutide decreased the A- and B-type natriuretic peptides significantly in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant T2D, suggesting a beneficial mechanism of liraglutide in T2D patients with HFrEF.

Topics: Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart Failure; Humans; Liraglutide; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Betacoronavirus; Biphenyl Compounds; Cardiotonic Agents; Coronavirus Infections; COVID-19; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Early Termination of Clinical Trials; Glomerular Filtration Rate; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hospitalization; Humans; Hypotension; Natriuretic Peptide, Brain; Pandemics; Peptide Fragments; Pneumonia, Viral; SARS-CoV-2; Stroke Volume; Tetrazoles; Valsartan

To investigate the effect of the sodium-glucose co-transporter-2 inhibitor empagliflozin on N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure (HF) and reduced ejection fraction (HFrEF).. Empire HF was an investigator-initiated, multi-center, double-blinded, placebo-controlled, randomized trial. Patients with mildly symptomatic HFrEF, mean (standard deviation (SD)) age 64 (11) years, 85% male, and mean left ventricular ejection fraction 29% (8), on recommended HF therapy were assigned to receive either empagliflozin 10 mg once daily or placebo for 12 weeks. The primary endpoint was the between-group difference in the change of NT-proBNP from baseline to 12 weeks. In total, 95 patients were assigned to empagliflozin and 95 to placebo. No significant difference in the change of NT-proBNP with empagliflozin versus placebo was observed [Empagliflozin: baseline, median (interquartile range (IQR)) 582 (304-1020) pg/mL, 12 weeks, 478 (281-961) pg/mL; Placebo: baseline, 605 (322-1070) pg/mL, 12 weeks, 520 (267-1075) pg/mL, adjusted ratio of change empagliflozin/placebo 0.98; 95% confidence interval (CI) 0.82-1.11, P = 0.7]. Further, no significant difference was observed in accelerometer-measured daily activity level [adjusted mean difference of change, empagliflozin versus placebo, -26.0 accelerometer counts; 95% CI -88.0 to 36.0, P = 0.4] or Kansas City Cardiomyopathy Questionnaire Overall Summary Score [adjusted mean difference of change, empagliflozin versus placebo 0.8; 95% CI -2.3 to 3.9, P = 0.6].. In low-risk patients with HFrEF with mild symptoms and on recommended HF therapy, empagliflozin did not change NT-proBNP after 12 weeks. Further, no change in daily activity level or health status was observed.

Topics: Accelerometry; Activities of Daily Living; Benzhydryl Compounds; Double-Blind Method; Female; Glucosides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Sorbitol; Stroke Volume

Fluid overload is associated with mortality in haemodialysis patients, and 30% of patients remain fluid-overloaded after dialysis. The aim of this study was to evaluate if implementation of Recova. The impact of the implementation was measured as the proportion of participants at an adequate target weight at the end of the study, assessed as change in symptoms, hydration status, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Nurses were instructed to use Recova every 2 weeks, and the process of the intervention was measured as frequencies of fluid status assessments, bioimpedance measurements, and target weight adjustments.. Forty-nine patients at two haemodialysis units were enrolled. In participants with fluid overload (. Implementation of Recova in haemodialysis care increased the monthly frequencies of bioimpedance measurements and target weight adjustments, and it contributed to symptom reduction.. The Uppsala County Council Registry of Clinical Trials: FoU 2019-0001-15.

Topics: Aged; Aged, 80 and over; Algorithms; Blood Pressure; Decision Support Techniques; Dielectric Spectroscopy; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Dialysis; Water-Electrolyte Imbalance

Topics: Biomarkers; Databases, Factual; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Racial Groups

Silent heart failure after myocardial infarction has not been effectively treated. Atorvastatin has certain efficacy in the treatment of heart failure. Our clinical study aimed to investigate the effectiveness of atorvastatin in patients with asymptomatic heart failure after myocardial infarction.. A total of 162 patients with asymptomatic heart failure after myocardial infarction in our hospital from August 2018 to August 2019 were randomly divided into the observation group (81 cases were treated with atorvastatin on the basis of routine therapy) and the control group (81 cases were treated with routine symptomatic treatment). The clinical curative effect, the level of related inflammatory cytokines, cardiac function index, and vascular endothelial function were compared between the two groups.. Before intervention, there was no significant difference in tumor necrosis factor (TNFα), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), plasma N-terminal B-type natriuretic peptide (NT-ProBNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular posterior wall thickness (LVPWT), asymmetric dimethyarginine (ADMA), activity of nitric oxide synthase (NOS), nitric oxide (NO) and flow-mediated dilation (FMD) between the two groups. After intervention, TNFα, hs-CRP, IL-6, NT-ProBNP, LVEF, LVEDD, LVESD, LVPWT, ADMA, NOS, NO, and FMD were improved in both groups. The clinical curative effect, TNFα, hs-CRP, IL-6, NT-ProBNP, LVEF, LVEDD, LVESD, LVPWT, ADMA, NOS, NO, and FMD in the observation group showed significantly greater results than those in the control group (P < 0.05).. Atorvastatin exerted a great effect in treating asymptomatic heart failure after myocardial infarction, which can evidently reduce the level of related inflammatory cytokines, improve cardiac function, and regulate vascular endothelial function. Hence, atorvastatin is considered a valid and alternative approach in clinical practice.

Topics: Atorvastatin; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

To investigate the clinical effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures.. Oldest-old patients over 80 years old with perioperative heart failure and hip fractures were randomly divided into the control and observation groups, with 50 patients in each group. All patients in both groups were treated with conventional anti-heart failure therapy and levosimendan, whereas patients in the observation group additionally received Xinkeshu tablets. Clinical manifestations; left ventricular ejection fraction (LVEF); left ventricular end-diastolic dimension (LVEDD); left ventricular end-systolic dimension (LVESD); B-type natriuretic peptide (BNP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) levels; and self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were compared between before and after treatment to evaluate the curative effects of Xinkeshu combined with levosimendan.. After treatment, the efficacy rate was significantly higher in the observation group than in the control group. LVEF and the levels of SOD and NO were higher in the observation group than in the control group after treatment. However, LVEDD; LVESD; BNP, MDA, and ET-1 levels; and the SAS and SDS scores were lower after treatment in the observation group than in the control group.. Levosimendan combined with Xinkeshu can improve cardiac function, alleviate oxidative stress, and relieve anxiety and depression in oldest-old patients with perioperative heart failure and hip fracture.

Topics: Aged; Aged, 80 and over; Drug Therapy, Combination; Drugs, Chinese Herbal; Endothelin-1; Female; Heart Failure; Hip Fractures; Humans; Male; Malondialdehyde; Natriuretic Peptide, Brain; Nitric Oxide; Simendan; Treatment Outcome

The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization.. Vericiguat compared with placebo reduced the primary outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH) in patients with HF with reduced ejection fraction (HFrEF) in the VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial. Because an interaction existed between treatment and the primary outcome according to pre-specified quartiles of NT-proBNP at randomization, we examined this further.. This study evaluated the NT-proBNP relationship with the primary outcome in 4,805 of 5,050 patients as a risk-adjusted, log-transformed continuous variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented.. A reduction in the primary composite endpoint and its CVD and HFH components was observed in patients on vericiguat compared with subjects on placebo with NT-proBNP levels up to 8,000 pg/ml. This provided new insight into the benefit observed in high-risk patients with worsening HFrEF. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [MK-1242-001] [VICTORIA]; NCT02861534).

Topics: Aged; Biomarkers; Female; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Pyrimidines; Stroke Volume

Growth hormone (GH) therapy in heart failure (HF) is controversial. We investigated the cardiovascular effects of GH in patients with chronic HF due to ischemic heart disease.. In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66 years; 95% male) with ischemic HF (ejection fraction [EF] < 40%) to a 9-month treatment with either recombinant human GH (1.4 mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP).. No changes in cardiac structure or systolic function were identified in either treatment group; nor did GH treatment affect QoL or functional class. In the GH group, circulating levels of IGF-1 doubled from baseline (+105%; p < 0.001) and NT-proBNP levels halved (-48%; p < 0.001) during the treatment period, with subsequently a partial return of both towards baseline levels. No changes in IGF-1 or NT-proBNP were observed in the placebo group at any time during the study.. In patients with chronic ischemic HF, nine months of GH treatment was associated with significant increases in levels of IGF-1 and reductions in levels of NT-proBNP, but did not affect cardiac structure, systolic function or functional capacity.

Topics: Aged; Biomarkers; Case-Control Studies; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Human Growth Hormone; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

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

EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials.. EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists.. When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Cardiovascular Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Patients admitted for acute heart failure (HF) are at high risk of readmission and death, especially in the 90 days following discharge. We aimed to assess the safety and efficacy of early optimization of oral HF therapy with beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNi), and mineralocorticoid receptor antagonists (MRA) on 90-day clinical outcomes in patients admitted for acute HF.. In a multicentre, randomized, open-label, parallel-group study, a total of 900 patients will be randomized in a 1:1 ratio to either 'usual care' or 'high-intensity care'. Patients enrolled in the usual care arm will be discharged and managed according to usual clinical practice at the site. In the high-intensity care arm, doses of oral HF medications - including a BB, ACEi or ARB, and MRA - will be up-titrated to 50% of recommended doses before discharge and to 100% of recommended doses within 2 weeks of discharge. Up-titration will be delayed if the patients develop worsening symptoms and signs of congestion, hyperkalaemia, hypotension, bradycardia, worsening of renal function or significant increase in N-terminal pro-B-type natriuretic peptide between visits. The primary endpoint is 90-day all-cause mortality or HF readmission.. STRONG-HF is the first study to assess whether rapid up-titration of evidence-based guideline-recommended therapies with close follow-up in a large cohort of patients discharged from an acute HF admission is safe and can affect adverse outcomes during the first 90 days after discharge.. ClinicalTrials.gov Identifier NCT03412201.

Topics: Acute Disease; Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cause of Death; Female; Growth Differentiation Factor 15; Guideline Adherence; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Neprilysin; Patient Admission; Patient Readmission; Patient Safety; Peptide Fragments; Survival Rate; Treatment Outcome