natriuretic-peptide--brain and Heart-Failure--Systolic

From previous systematic reviews and meta-analyses, there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure (HF); however, the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production (VE/VCO2) slope has not been evaluated. The primary aim of the proposed study is to determine the effect of aerobic exercise training (AEX) on the VE/VCO2 slope and NTproBNP. The following databases (up to February 30, 2013) were searched with no language limitations: CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January 1929). We screened reference lists of articles and also conducted an extensive hand search of the literature. Randomized controlled trials of exercise-based interventions with 2-month follow-up or longer compared to usual medical care or placebo were included. The study population comprised adults aged between 18 and 65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed the risk of bias using PEDro scale. We calculated mean differences (MD) or standardized mean differences between intervention and control groups for outcomes with sufficient data; for other outcomes, we described findings from individual studies. Eight studies involving a total of 408 participants met the inclusion criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO2 slope (4 studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a MD of -817.75 [95 % confidence interval (CI) -929.31 to -706.19]. Mean differences across VE/VCO2 slope were -6.55 (95 % CI -7.24 to -5.87). Those patients' characteristics and exercise were similar (frequency = 3-5 times/week; duration = 20-50 min/day; intensity = 60-80 % of VO2 peak) on the included studies. Moreover, the risk of bias across all studies was homogeneous (PEDro scale = 7-8 points). However, based on the statistical analysis, the heterogeneity among the studies was still high, which is related to the variable characteristics of the studies. Aerobic exercise may be effective at improving NTproBNP and the VE/VCO2 slope in systolic HF patients, but these effects are limited to a specific HF population meeting specific inclusion criter

Topics: Biomarkers; Carbon Dioxide; Exercise; Exercise Therapy; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards.. Data were obtained from 5508 patients from 10 studies in the UK, New Zealand, Europe, and USA. All have had NT-proBNP analysis and echocardiography. The median age was 62 years (range 18-100 years) with a prevalence of reduced left ventricular systolic function (left ventricular ejection fraction < or =40%) of 18%. In a receiver operating characteristic curve analysis, overall area under the curve (AUC) was 0.89. When looking at different age groups, AUC was highest (0.95) for <50 years, intermediate (0.90) for 50-75 years, and lowest (0.82) for >75 years. Using optimized decision limits, sensitivity, specificity, and negative predictive values (NPVs) were: <50 years (50 ng/L): 99.2, 57.2, and 99.7%; 50-75 years (75 ng/L): 95.9, 51.0, and 96.8%; and >75 years (250 ng/L): 87.9, 53.7, and 92.4%, respectively. Using only a single decision value (125 ng/L for all ages) gave sensitivities of 89.1, 91.9, and 94.3%; specificities of 84.0, 69.1, and 29.3% and NPVs of 97.7, 97.6, and 93.4%. A decision value of 400 ng/L for all ages gave much lower sensitivities.. In a large population of patients in primary care, the use of age-stratified NT-proBNP decision limits considerably improves performance over current standards, with an excellent NPV for exclusion of reduced left ventricular systolic function.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values; ROC Curve; Sensitivity and Specificity; Young Adult

We set out to review the validity of tests for B type natriuretic peptide (BNP) and N-terminal pro BNP (NTproBNP) in the diagnosis of clinical heart failure (HF) in primary care and hospital settings and to examine the effect of age. We also examined the accuracy of the test in population screening for left ventricular systolic dysfunction.. Medline and Embase were searched systematically till June 2005. Forty-seven studies were identified for systematic review and 27 were included in meta-analyses. Test performance was summarized as the diagnostic odds ratio (DOR). As a secondary data analysis, this paper does not require ethical approval.. In groups of symptomatic patients with average age less than 80 years, the summary DOR of 27 for BNP equates to a sensitivity of 85% and specificity of 84% in the detection of clinical HF. Summary of head-to-head studies shows BNP is a better indicator than NTproBNP. The performance of both tests decreased with the age of patients, the DOR declining by a factor of 2.0 for BNP and 2.5 for NTproBNP for each decade of increasing age. BNP correlated better to clinical status than to echocardiographic parameters, and test performance was similar in acute inpatient and general practice settings.. Tests for BNP are helpful in the diagnosis of clinical HF or in screening for left ventricular systolic dysfunction and are superior to NTproBNP. In the clinical setting, test performance declined with increasing patient age.

Topics: Aged; Aged, 80 and over; Female; Heart Failure, Systolic; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left

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

The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported.. The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).. Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP.. In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration. The NT-proBNP concentration after treatment with empagliflozin better informs subsequent prognosis than pretreatment concentrations. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).

Topics: Aged; Benzhydryl Compounds; Female; Glucosides; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors

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

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

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

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

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

The characteristics and outcomes of patients hospitalized with acute systolic heart failure (HF) and normal admission B-type natriuretic peptide (BNP) has not been previously explored.. Using the ESCAPE trial data, we compared patients with acute HF and left ventricular ejection fraction (LVEF) ≤30% who have either normal or elevated BNP on the day of hospitalization. The study endpoints were 30-day and 6-month mortality, all-cause rehospitalization and rehospitalization for HF.. Patients hospitalized with acute systolic HF and normal admission BNP had no significant differences in the degree of congestion and post-discharge outcomes compared with those with elevated BNP. A normal BNP in this instance was not valuable for diagnostic or prognostic purposes.

Topics: Acute Disease; Biomarkers; Disease Progression; Female; Follow-Up Studies; Heart Failure, Systolic; Hospital Mortality; Humans; Male; Middle Aged; Morbidity; Natriuretic Peptide, Brain; Patient Admission; Patient Readmission; Prognosis; Retrospective Studies; Stroke Volume; Survival Rate; Time Factors; United States; Ventricular Function, Left

While abnormal left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood.. Patients enrolled in the RELAX trial of sildenafil in HFpEF (LV ejection fraction ≥50%) in whom two-dimensional, speckle-tracking LV GLS was possible (n = 187) were analysed. The distribution of LV GLS and its associations with clinical characteristics, LV structure and function, biomarkers, exercise capacity and quality of life were assessed. Baseline median LV GLS was -14.6% (25th and 75th percentile, -17.0% and -11.9%, respectively) and abnormal (≥ - 16%) in 122/187 (65%) patients. Patients in the tertile with the best LV GLS had lower N-terminal pro-brain natriuretic peptide (NT-proBNP) [median 505 pg/mL (161, 1065) vs. 875 pg/mL (488, 1802), P = 0.008) and lower collagen III N-terminal propeptide (PIIINP) levels [median 6.7 µg/L (5.1, 8.1) vs. 8.1 µg/L (6.5, 10.5), P = 0.001] compared with the tertile with the worst LV GLS. There was also a modest linear relationship with LV GLS and log-transformed NT-proBNP and PIIINP (r = 0.29, P < 0.001 and r = 0.19, P = 0.009, respectively). We observed no linear association of LV GLS with Minnesota Living with Heart Failure scores, 6-min walk distance, peak oxygen consumption, or expiratory minute ventilation/carbon dioxide excretion slope.. Impaired LV GLS is common among HFpEF patients, indicating the presence of covert systolic dysfunction despite normal LV ejection fraction. Impaired LV GLS was associated with biomarkers of wall stress and collagen synthesis and diastolic dysfunction but not with quality of life or exercise capacity, suggesting other processes may be more responsible for these aspects of the HFpEF syndrome.

Topics: Aged; Aged, 80 and over; Biomarkers; Double-Blind Method; Echocardiography; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Procollagen; Quality of Life; Retrospective Studies; Stroke Volume; Time Factors; Ventricular Function, Left

We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy.. We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10 µg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P < 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo.. Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

Topics: Aged; Asymptomatic Diseases; Atrial Natriuretic Factor; Cyclic GMP; Double-Blind Method; Echocardiography; Female; Fluid Therapy; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Infusions, Subcutaneous; Kidney; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Sodium

Increased circulating endostatin levels have been demonstrated in progressive cardiovascular (CV) and renal disorders. We investigated the predictive value of endostatin in patients with chronic heart failure (HF) and the association between endostatin and renal function.. The interaction between serum endostatin, estimated glomerular filtration rate (eGFR) and predefined endpoints, including the primary endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke; n = 397), all-cause mortality (n = 410), CV death (n = 335) or the coronary endpoint (n = 317), was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, who were randomly assigned to 10 mg rosuvastatin or placebo.. In the population as a whole, endostatin added no predictive information after full multivariable adjustment including eGFR and N-terminal pro-brain natriuretic peptide. Serum endostatin was strongly correlated with eGFR (r = 0.59, p < 0.001). After full multivariable adjustment, an association between high serum endostatin and increased risk of all-cause mortality and decreased risk of the primary and coronary endpoints was seen in HF patients with impaired and preserved renal function, respectively.. Endostatin added no predictive information regarding the adverse outcome in patients with chronic systolic HF of ischemic etiology. An increased risk of all-cause mortality was seen in patients with decreased renal function.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Endostatins; Female; Fluorobenzenes; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunoenzyme Techniques; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Pyrimidines; Rosuvastatin Calcium; Sulfonamides

Preclinical studies suggest that neuromodulation with thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function and remodeling in systolic heart failure (HF).. The purpose of this study was to evaluate the safety and efficacy of a SCS system for the treatment of systolic HF.. We performed a prospective, multicenter pilot trial in patients with New York Heart Association (NYHA) class III HF, left ventricular ejection fraction (LVEF) 20%-35%, and implanted defibrillator device who were prescribed stable optimal medical therapy. Dual thoracic SCS leads were used at the T1-T3 level. The device was programmed to provide SCS for 24 hours per day (50 Hz at pulse width 200 μs).. We enrolled 22 patients from 5 centers:17 patients underwent implantation of a SCS device and 4 patients who did not fulfill the study criteria served as nontreated controls. No deaths or device-device interactions were noted during the 6-month period in the 17 SCS-treated patients. Fifteen of 17 completed the efficacy endpoint assessments: composite score improved by 4.2 ± 1.3, and 11 patients (73%) showed improvement in ≥4 of 6 efficacy parameters. There was significant improvement in NYHA class (3.0 vs 2.1, P = .002; 13/17 improved); Minnesota Living with Heart Failure Questionnaire (42 ± 26 vs 27 ± 22, P = .026; 12/17 improved); peak maximum oxygen consumption (14.6 ± 3.3 vs 16.5 ± 3.9 mL/kg/min, P = .013; 10/15 improved); LVEF (25% ± 6% vs 37% ± 8%, P<.001; 14/16 improved); and LV end-systolic volume (174 ± 57 vs 137 ± 37 mL, P = .002; 11/16 improved) but not in N-terminal prohormone brain natriuretic peptide. No such improvements were observed in the 4 nontreated patients.. The results of this first-in-human trial suggest that high thoracic SCS is safe and feasible and potentially can improve symptoms, functional status, and LV function and remodeling in patients with severe, symptomatic systolic HF.

Topics: Aged; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Prospective Studies; Spinal Cord; Spinal Cord Stimulation; Surveys and Questionnaires; Thoracic Vertebrae; Treatment Outcome; Ventricular Function, Left

Heart rate (HR) reduction is associated with improved outcomes in patients with heart failure (HF) and biomarkers can be a valuable diagnostic tool in HF management. The primary aim of our study was to evaluate the short-term (6 months) effect of ivabradine on N-terminal pro B-type natriuretic peptide (NT-proBNP), CA-125, and cystatin-C values in systolic HF outpatients, and secondary aim was to determine the relationship between baseline HR and the NT-proBNP, CA-125, cystatin-C, and clinical status variation with ivabradine therapy.. Ninety-eight patients (mean age: 65.81 ± 10.20 years; 33 men), left ventricular ejection fraction < 35% with Simpson method, New York Heart Association (NYHA) class II-III, sinus rhythm and resting HR > 70/min, optimally treated before the study were included. Among them, two matched groups were formed: the ivabradine group and the control group. Patients received ivabradine with an average (range of 10-15) mg/day during 6 months of follow-up. Blood samples for NT-proBNP, CA-125, and cystatin-C were taken at baseline and at the end of a 6-month follow-up in both groups.. There was a significant decrease in NYHA class in the ivabradine group (2.67 ± ± 0.47 vs. 1.85 ± 0.61, p < 0.001). When ivabradine and control groups were compared, a significant difference was also found in NHYA class 6 months later (p = 0.013). A significant decrease was found in HR in the ivabradine and control groups (84.10 ± 8.76 vs. 68.36 ± ± 8.32 bpm, p = 0.001; 84.51 ± 10 vs. 80.40 ± 8.3 bpm, p = 0.001). When both groups were compared, a significant difference was also found in HR after 6 months (p = 0.001). A significant decrease was found in cystatin-C (2.10 ± 0.73 vs. 1.50 ± 0.44 mg/L, p < 0.001), CA-125 (30.09 ± 21.08 vs. 13.22 ± 8.51 U/mL, p < 0.001), and NT-proBNP (1,353.02 ± 1,453.77 vs. 717.81 ± 834.76 pg/mL, p < 0.001) in the ivabradine group. When ivabradine and control groups were compared after 6 months, a significant decrease was found in all HF parameters (respectively; cystatin-C: p = 0.001, CA-125: p = 0.001, NT-proBNP: p = 0.001). Creatinine level was significantly decreased and glomerular filtration rate (GFR) was significantly increased in the ivabradine group (1.02 ± 0.26 vs. 0.86 ± 0.17, creatinine: p = 0.001; 79.26 ± 18.58 vs. 92.48 ± 19.88, GFR: p = 0.001). There was no significant correlation between NYHA classes (before and after ivabradine therapy) and biochemical markers, or HR.. In the outpatients with systolic HF, persistent resting HF > 70/min with optimal medical therapy, the NT-proBNP, CA-125, and cystatin-C reductions were obtained with ivabradine treatment. Measurement of NT-proBNP, CA-125, and cystatin-C may prove to be useful in biomarker panels evaluating ivabradine therapy response in HF patients.

Topics: Aged; Benzazepines; Biomarkers; CA-125 Antigen; Cardiovascular Agents; Cystatin C; Down-Regulation; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Turkey; Ventricular Function, Left

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

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

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

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

The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of <1,000 pg/ml compared with usual care in high-risk patients with systolic heart failure (HF).. Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF.. GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of <1,000 pg/ml. Patients in either arm of the study are followed up at regular intervals and after treatment adjustments for a minimum of 12 months. The primary endpoint of the study is time to cardiovascular death or first hospitalization for HF. Secondary endpoints include time to cardiovascular death and all-cause mortality, cumulative mortality, health-related quality of life, resource use, cost-effectiveness, and safety.. The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840).

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiac Resynchronization Therapy; Evidence-Based Medicine; Exercise Therapy; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Patient Care Planning; Peptide Fragments

Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers.. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers.. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders.. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function.

Topics: Aged; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency; Troponin I

This study was designed to evaluate a new NT-proBNP monitoring concept in outpatients with systolic heart failure (HF).. This was a multicentre, prospective randomized open-label blinded endpoint study. A total of 407 systolic HF patients were allocated to either clinical management (n = 208) or clinical management + NT-proBNP monitoring (n = 199) and followed for 2.5 years. If NT-proBNP increased >30%, a clinical checklist was completed and treatment initiated. The patients were matched at randomization and were 73 years old, 25% were females, 85% were NYHA class I-II, LVEF was 30%, and NT-proBNP 1955 pg/mL. NT-proBNP monitoring did not improve outcome, the hazard ratio for the primary composite endpoint (death or a cardiovascular admission) being 0.96 [95% confidence interval (CI) 0.71-1.29, P = 0.766]. NT-proBNP monitoring did not induce a significant change in the pharmacological strategy (P > 0.05 for all comparisons). In patients in whom NT-proBNP increased >30% (25% of the patients) during follow-up, a higher frequency of admission (69% vs. 47%, P = 0.002), a higher number of admission days (14 vs. 5 days, P = 0.003) and number of admissions (2 vs. 1, P = 0.009), and a lower quality of life (P = 0.032) and a poorer functional class (37% vs. 18% in NYHA class III-IV, P < 0.001) were observed.. Adding serial measurements of NT-proBNP to optimal clinical management was not associated with a change in pharmacological strategy and did not improve outcome. However, survivors in whom NT-proBNP increased >30% showed a poorer functional class, clinical outcome, and quality of life.. www.centerwatch: 173491 (NorthStar).

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiac Output; Cardiovascular Agents; Double-Blind Method; Female; Follow-Up Studies; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prognosis; Prospective Studies; Registries; Severity of Illness Index

Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.. Patients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death.. PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF.. NCT01035255.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Drug Combinations; Enalapril; Heart Failure, Systolic; Hospitalization; Humans; Morbidity; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Prospective Studies; Single-Blind Method; Survival Rate; Tetrazoles; Valsartan

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

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

Heart failure (HF) is a common condition with which high mortality, morbidity, and poor quality of life are associated. It has previously been shown that use of HF management programmes (HFMPs) in HF clinics can be beneficial. The purpose of this study was to evaluate if the use of HFMPs also has beneficial effects on HF patients in primary healthcare (PHC).. This is a randomized, prospective, open-label study including 160 patients from five PHC centres with systolic HF and a mean age of 75 years (standard deviation 7.8). In the intervention group, an intensive follow-up was performed by HF nurses and physicians providing information and education about HF and the optimization of HF treatment according to recognized guidelines. There was a significant improvement of composite endpoints in the intervention group. Significantly more patients with reduced N-terminal pro brain natriuretic peptide (P = 0.012), improved cardiac function (P = 0.03), fewer healthcare contacts (P = 0.04), and fewer emergency room visits and admittances (P = 0.0002 and P = 0.03, respectively) could be seen in the intervention group when compared with the control group.. The use of a HFMP in a PHC setting was found to have beneficial effects in terms of reducing the number of healthcare contacts and hospital admissions, and improving cardiac function in patients with systolic HF, even if the result should be interpreted with caution. It can therefore be recommended that HFMPs should be used in PHC.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Disease Management; Diuretics; Female; Follow-Up Studies; Furosemide; General Practice; Guideline Adherence; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain; Nurse Clinicians; Patient Care Team; Patient Education as Topic; Patient Readmission; Peptide Fragments; Primary Health Care; Prospective Studies; Stroke Volume; Sweden

The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP.. This study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers.. Fifty-six white patients with systolic HF and normal cholesterol levels (age 72 [13] years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35 [13]%; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups).. Serum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01).. Long-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Atorvastatin; Biomarkers; Chi-Square Distribution; Cholesterol; Collagen; Collagen Type I; Down-Regulation; Female; Heart Failure, Systolic; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Ireland; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Procollagen; Prospective Studies; Pyrroles; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Up-Regulation; Ventricular Function, Left

To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective.. Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction = 0.036). Among patients with below the median plasma concentrations of galectin-3 (≤ 19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95% confidence interval (CI), 0.46-0.92; P= 0.014], lower total mortality (HR 0.70; 95% CI, 0.50-0.98; P= 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95% CI, 0.54-0.98; P= 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (<102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95% CI, 0.16-0.67; P= 0.002).. Patients with systolic HF of ischaemic aetiology who have galectin-3 values <19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.

Topics: Aged; Biomarkers; C-Reactive Protein; Female; Fluorobenzenes; Galectin 3; Heart Failure, Systolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Lipid Metabolism; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Pyrimidines; Rosuvastatin Calcium; Stroke; Sulfonamides; Treatment Outcome

The purpose of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SC B-type natriuretic peptide (BNP) administration in human Stage C heart failure (HF).. B-Type natriuretic peptide is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin inhibiting, and lusitropic properties. We have previously demonstrated that chronic cardiac hormone replacement with subcutaneous (SC) administration of BNP in experimental HF resulted in improved cardiovascular function.. We performed a randomized double-blind placebo-controlled proof of concept study comparing 8 weeks of SC BNP (10 μg/kg bid) (n = 20) with placebo (n = 20) in patients with ejection fraction <35% and New York Heart Association functional class II to III HF. Primary outcomes were left ventricular (LV) volumes and LV mass determined by cardiac magnetic resonance imaging. Secondary outcomes include LV filling pressure by Doppler echo, humoral function, and renal function.. Eight weeks of chronic SC BNP resulted in a greater reduction of LV systolic and diastolic volume index and LV mass index as compared with placebo. There was a significantly greater improvement of Minnesota Living with Heart Failure score, LV filling pressure as demonstrated by the reductions of E/e' ratio, and decrease in left atrial volume index as compared with placebo. Glomerular filtration rate was preserved with SC BNP, as was the ability to activate plasma 3',5'-cyclic guanosine monophosphate (p < 0.05 vs. placebo).. In this pilot proof of concept study, chronic protein therapy with SC BNP improved LV remodeling, LV filling pressure, and Minnesota Living with Heart Failure score in patients with stable systolic HF on optimal therapy. Renin-angiotensin was suppressed, and glomerular filtration rate was preserved. Subcutaneous BNP represents a novel, safe, and efficacious protein therapeutic strategy in human HF. Further studies are warranted to determine whether these physiologic observations can be translated into improved clinical outcomes and ultimately delay the progression of HF. (Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy; NCT00252187).

Topics: Double-Blind Method; Drug Administration Schedule; Female; Heart Failure, Systolic; Humans; Injections, Subcutaneous; Male; Natriuretic Peptide, Brain; Pilot Projects; Ventricular Remodeling

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

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

In heart failure (HF), a defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. PDE5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. In a cohort of systolic HF patients, we tested the effects of PDE5 inhibition (sildenafil) on LV ejection fraction, diastolic function, cardiac geometry, and clinical status.. Forty-five HF patients (New York Heart Association class II-III) were randomly assigned to placebo or sildenafil (50 mg three times per day) for 1 year, with assessment (6 months and 1 year) of LV ejection fraction, diastolic function, geometry, cardiopulmonary exercise performance, and quality of life. In the sildenafil group only, at 6 months and 1 year, LV ejection fraction, early diastolic tissue Doppler velocities (E') at the mitral lateral (from 4.62 to 5.20 and 5.19 m/s) and septal (from 4.71 to 5.23 and 5.24 m/s) annuli significantly increased, whereas the ratio of early transmitral (E) to E' lateral decreased (from 13.1 to 9.8 to 9.4) (P<0.01). Changes were accompanied by a reverse remodeling of left atrial volume index (from 32.0 to 29.0 and 29.1 mL/m(2); P<0.01) and LV mass index (from 148.0 to 130.0 and 128.0 g/m(2); P<0.01). Furthermore, sildenafil improved exercise performance (peak Vo(2)), ventilation efficiency (ventilation to CO(2) production slope), and quality of life (P<0.01). Minor adverse effects were noted: flushing in 4 and headache in 2 treated patients.. Findings confirm that in HF, sildenafil improves functional capacity and clinical status and provide the first human evidence that LV diastolic function and cardiac geometry are additional targets of benefits related to chronic PDE5 inhibition.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Diastole; Double-Blind Method; Exercise Test; Heart Failure, Systolic; Humans; Longitudinal Studies; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Ventricular Dysfunction, Left

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

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

We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and β-blockers).. From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

Topics: Aged; Canrenone; Double-Blind Method; Female; Heart Failure, Systolic; Heart Ventricles; Humans; Male; Metabolic Syndrome; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Placebos; Procollagen

We hypothesized an impaired renal endocrine and natriuretic response to volume expansion (VE) in humans with pre-clinical systolic dysfunction (PSD) and pre-clinical diastolic dysfunction (PDD). We further hypothesized that exogenous B-type natriuretic peptide (BNP) could rescue an impaired natriuretic response in PSD and PDD.. Recent reports suggest that in early systolic heart failure (HF), there is an impaired natriuretic response to acute VE.. PSD was defined as left ventricular ejection fraction <40% without HF symptoms. PDD was defined as ejection fraction >50%, moderate to severe diastolic dysfunction by Doppler criteria, and no HF symptoms. A double-blinded, placebo-controlled, crossover study was employed to determine the renal response to VE (0.25 ml/kg/min of normal saline for 60 min) in the presence and absence of exogenous BNP. Twenty healthy control subjects, 20 PSD subjects, and 18 PDD subjects participated.. In healthy control subjects, urinary cyclic guanosine monophosphate (cGMP) and natriuresis increased after VE. In contrast, among PSD and PDD subjects, there was a paradoxical decrease in urinary cGMP and attenuated natriuresis. Pre-treatment with subcutaneous BNP resulted in similar increases in both urinary cGMP and natriuresis among healthy normal, PSD, and PDD subjects.. In PSD and PDD, there is impaired renal cGMP activation, which contributes to impaired natriuresis in response to VE. Impaired activation of urinary cGMP and reduced natriuresis may contribute to volume overload and the progression of HF among PSD and PDD subjects. Importantly, the impaired renal excretory response to VE is rescued by exogenous BNP in PSD and PDD.

Topics: Adult; Aged; Blood Volume; Case-Control Studies; Cross-Over Studies; Double-Blind Method; Female; Guanosine Monophosphate; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Sodium

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

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

Diastolic dysfunction in long-term heart failure is accompanied by abnormal neurohormonal control and ventricular stiffness. The diastolic phase is determined by a balance between pressure gradients and intrinsic ventricular wall properties: according to a mathematical model, the latter (ie, left ventricular [LV] elastance, K(LV)) may be calculated by the formula: K(LV) = (70/[DT-20])(2) mm Hg/mL, where DT is the transmitral Doppler deceleration time.. In 54 patients with chronic systolic heart failure (39 men, 15 women; age 65 +/- 10 years; New York Heart Association [NYHA], 2.3 +/- 0.9; ejection fraction [EF], 32% +/- 5%), we analyzed the relationship between K(LV) and an index of neurohormonal derangement (levels of brain natriuretic peptide [BNP]), and investigated whether 3 months of physical training could modulate diastolic operating stiffness. Patients were randomized to physical training (n = 27) or to a control group (n = 27). Before and after training, patients underwent Doppler echocardiogram and cardiopulmonary stress test. At baseline, ventricular stiffness was related to BNP levels (P < .01). Training improved NYHA class, exercise performance, and estimated pulmonary pressure. BNP was reduced. Ventricular volumes, mean blood pressure, and EF remained unchanged. A 27% reduction of elastance was observed (K(LV), 0.111 +/- 0.044 from 0.195 +/- 0.089 mm Hg/mL; P < .01), whose magnitude was related to changes in BNP (P < .05) and to K(LV) at baseline (P < .01). No changes in K(LV) were observed in controls after 3 months (0.192 +/- 0.115 from 0.195 +/- 0.121 mm Hg/mL).. In heart failure, left ventricular diastolic stiffness is related to neurohormonal derangement and is modified by physical training. This improvement in LV compliance could result from a combination of hemodynamic improvement and regression of the fibrotic process.

Topics: Aged; Cardiomyopathy, Dilated; Diastole; Exercise; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Chronic (systolic) heart failure (CHF) is a common and disabling condition. Adherence to evidence-based guidelines in primary care has been shown to improve health outcomes. The aim was to explore the impact of a multidisciplinary educational intervention for general practitioners (GPs) (Train the trainer = TTT) on patient and performance outcomes.. This paper presents the key findings from the trial and discusses the lessons learned during the implementation of the TTT trial. Primary care practices were randomly assigned to the TTT intervention or to the control group. 37 GPs (18 TTT, 19 control) were randomised and 168 patients diagnosed with ascertained CHF (91 TTT, 77 control) were enrolled. GPs in the intervention group attended four meetings addressing clinical practice guidelines and pharmacotherapy feedback. The primary outcome was patient self-reported quality of life at seven months, using the SF-36 Physical Functioning scale. Secondary outcomes included other SF-36 scales, the Kansas City Cardiomyopathy Questionnaire (KCCQ), total mortality, heart failure hospital admissions, prescribing, depressive disorders (PHQ-9), behavioural change (European Heart Failure Self-Care Behaviour Scale), patient-perceived quality of care (EUROPEP) and improvement of heart failure using NT-proBNP-levels. Because recruitment targets were not achieved an exploratory analysis was conducted.. There was high baseline achievement in both groups for many outcomes. At seven months, there were no significant mean difference between groups for the primary outcome measure (-3.3, 95%CI -9.7 to 3.1, p = 0.30). The only difference in secondary outcomes related to the prescribing of aldosterone antagonists by GPs in the intervention group, with significant between group differences at follow-up (42 vs. 24%, adjusted OR = 4.0, 95%CI 1.2-13; p = 0.02).. The intervention did not change the primary outcome or most secondary outcomes. Recruitment targets were not achieved and the under-recruitment of practices and patients alongside a selection bias of participating GPs, prohibit definite conclusions, but the CI indicates a non-effectiveness of the intervention in this sample. We describe the lessons learned from conducting the trial for the future planning and conduct of confirmatory trials in primary care.. ISRCTN08601529.

Topics: Adult; Education, Medical, Continuing; Follow-Up Studies; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Physicians, Family; Primary Health Care

Patients with systolic heart failure often have concomitant left ventricular (LV) diastolic dysfunction. Although in animal models diastolic dysfunction is associated with worsening exercise capacity and prognosis, information regarding these relationships in patients with established systolic heart failure (HF) is sparse.. HF-ACTION was a large, multicenter National Institutes of Health-funded trial of exercise training in systolic HF (LV ejection fraction [LVEF] < or = 35%) and included detailed Doppler-echocardiographic (echo) and cardiopulmonary exercise testing at baseline. We tested the hypothesis that echo measures of LV diastolic function predict key cardiopulmonary exercise outcomes, including aerobic exercise capacity (peak exercise oxygen consumption, VO(2)), distance in the 6-minute walk test (6MWD), and ventilatory efficiency (VE/VCO(2) slope) in patients with systolic HF.. Overall, 2,331 patients (28% women, median age 59 years, median LVEF 25%) were enrolled. There were significant bivariate correlations between echo diastolic function variables and peak VO(2) (inverse) and VE/VCO(2) slope (direct) that were strongest for ratio of early diastolic peak transmitral (MV) to myocardial tissue velocity (E/E'), peak MV early-to-late diastolic velocity ratio (E/A), and left atrial dimension (range of absolute r = 0.16-0.28). Both MV E/A and E/E' were more strongly related to all 3 exercise variables than was LVEF. The relationships of E/A and E/E' with 6MWD were weaker than with peak VO(2) or VE/VCO(2) slope. A multivariable model with peak VO(2) as the dependent variable, which included MV E/A and 9 demographic predictors including age, sex, race, body mass index, and New York Heart Association class, explained 40% of the variation in peak VO(2), with MV E/A explaining 6% of the variation. Including LVEF in the model explained less than an additional 1% of the variance in peak VO(2). In a multivariable model for VE/VCO(2) slope, MV E/A was the strongest independent echo predictor, explaining 10% of the variance. The relationship of LV diastolic function variables with 6MWD was weaker than with peak VO(2) or VE/VCO(2) slope.. In patients with systolic HF, LV early diastolic function is a modest independent predictor of aerobic exercise capacity and appears to be a better predictor than LVEF.

Topics: Data Collection; Diastole; Echocardiography, Doppler; Exercise Test; Exercise Tolerance; Female; Heart Failure; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Physical Endurance; Prognosis; Ventricular Dysfunction, Left; Ventricular Function, Left

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

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

Effect of statins on N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure has not been well elucidated. Purpose. To assess changes of NT-proBNP during short term use of simvastatin in patients with coronary heart disease (CHD) and chronic systolic heart failure. Patients and methods. Statin naive patients (n=70) with coronary heart disease (CHD), NYHA class II-IV hart failure and LV ejection fraction (EF) 35% or less after correction of treatment and 1 month of stabilization on standard therapy were randomized to open simvastatin 40 mg/day (n=36) or no statin (n=34). In 65.1% of pts (65.6 and 64.5% in statin and control groups, respectively) beta-blockers were either initiated or their dose was corrected during <> phase of the study. Blood plasma lipids, NT-proBNP were measured and echocardiography carried out at randomization and in 4 months. Seven patients were not restudied and analysis included data from 32 (statin) and 31 (control) patients. Results. Baseline characteristics of groups were similar. Addition of statin to standard therapy was associated with lowering of low density lipoprotein cholesterol (-42%) and triglycerides (-14%). Changes of other parameters were similar in both groups including equal increases of NT-proBNP (from 540.9 to 1082.2 fmol/ml, p<0.0001, and from 639.6 to 1119.72 fmol/ml, p<0.0001, in control and simvastatin group, respectively). Baseline NT-proBNP correlated negatively with ejection fraction and positively with left ventricular dimensions, heart failure class and blood serum creatinine. The patients were followed for 1 year. Baseline NT-proBNP level was related to hospitalizations because of heart failure exacerbation during this year. Conclusion. In a group of patients with systolic heart failure due to CHD and trivial relationships between baseline NT-proBNP level and characteristics of heart failure severity short term simvastatin use caused expected LDLCH lowering but was associated with NT-proBNP increase equal to that observed in control group. Rise of NT-proBNP in both groups was probably related to activation of beta-blocker therapy.

Topics: Coronary Artery Disease; Heart Failure, Systolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Natriuretic Peptide, Brain; Simvastatin

Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF.. The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events.. CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events.. In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.

Topics: Biomarkers; Chromogranin A; Heart Failure; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prognosis; Stroke Volume; Ventricular Function, Left

The aim of this study was to evaluate the roles of fibroblast growth factor 21 (FGF21) in heart failure patients with reduced ejection fraction and its association with Heart Failure with reduced Ejection Fraction (HFrEF).. The level of FGF21 was measured by enzyme-linked immunosorbent assay (ELISA) in 199 subjects enrolled in this study, including 128 subjects with HFrEF and 71 control subjects. The mean follow-up time was 13.36 months. The left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) percentage were evaluated by the 2D echocardiography. Serum brain natriuretic peptide (BNP) was measured in the routine clinical laboratory.. The serum FGF21 level was evidently higher in patients with HFrEF than in the control group (228.72 ± 24.04 vs. 171.60 ± 12.98,. FGF21 was independently associated with an increased risk of mortality and readmission HFrEF patients. Therefore, FGF21 has the potential to be a biomarker for the progression of HFrEF in patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Computational Biology; Disease Progression; Female; Fibroblast Growth Factors; Heart Disease Risk Factors; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Dysfunction, Left

The study aimed to assess the accuracy of two-dimensional speckle tracking echocardiography (2DSTE) to evaluate the left atrial (LA) function in patients with heart failure. And can it differentiate accurately between heart failure preserved ejection fraction (HFpEF, HF with mid-range ejection fraction (HFmrEF=EF 41-49%) and heart failure with reduced ejection fraction (HFrEF= EF<40%)? It included 186 patients of heart failure who were classified into 74 patients with HFpEF (LVEF>50%), 56 patients with HFmrEF (LVEF 41-49%), 56 patients with HFrEF (LVEF<40%), and 50 normal matched subjects. B-type natriuretic peptide (BNP) was more than 35 pg/mL for all patients. The conventional echocardiography evaluated left ventricle systolic and diastolic functions. The 2DSTE evaluated the LV global strain (LVGS), and strain and strain rate (SR) in each phase of LA function. LVGS was -19.3±2.3%, -18.0±1.7%, -16.1±2.0%, and -14.3±2.2 in controls, HFpEF, and HFmrEF, and HFrEF, respectively (p<0.0001); GPALS was 34.1±6.7%, 27.5±4.7%, 21.7±4.8% and 16.9±4.9% in controls, HFpEF, HFmrEF, HFrEF, respectively (p<0.0001); The GPACS was 14.8±4.3%, 12.3±2.2%, 9.7±2.3%, and 7.5±2.6%  in controls, HFpEF, HFmrEF, and HFrEF, respectively (p<0.0001); The PALS-PACS was 19.4±3%, 15.1±4.4%, 12.0±3.4%, and  9.3±3.3% in controls, HFpEF, HFmrEF, and HFrEF (p<0.0001). Therefore, early LA dysfunction in heart failure can be detected accurately and easily by speckle tracking technique that could be a promising independent tool to better understand of heart failure and its classification.

Topics: Echocardiography; Heart Failure; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Function, Left

Topics: Denmark; Follow-Up Studies; Heart Failure; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments

Brain‑derived neurotrophic factor (BDNF) is decreased in heart failure (HF), but whether serum BDNF concentration is related to the severity of HF with reduced left ventricular (LV) ejection fraction (LVEF) below 50% is uncertain.. We aimed to compare cardiac structure and function in ambulatory and clinically stable patients with HF and LVEF below 50% for lower and higher BDNF serum concentrations.. A total of 361 ambulatory patients with a compensated HF and LVEF below 50% underwent cardiac evaluation and measurement of serum BDNF and N‑terminal pro-B‑type natriuretic peptide (NT‑proBNP). Patients from the lower (below median) and higher (equal to or above median) BDNF serum concentration groups were compared by analysis of covariance (ANCOVA) adjusted for age, sex, body mass index, resting heart rate, and systolic blood pressure.. The patients were at a median age of 63.8 (interquartile range [IQR], 57.7-71.5) years and had a median LVEF of 31.0% (IQR, 23.0-37.4). Individuals with lower BDNF (<23.5 ng/ml) had significantly (P ≤0.05) more dilated right and left atria both before and after emptying, larger right ventricular end-diastolic diameter, LV end-systolic diameter, lower tricuspid annulus plane systolic excursion, shorter pulmonary acceleration time, higher mitral E to A waves ratio and mitral E wave to tissue Doppler e' wave ratio, and higher concentration of NT‑proBNP.. HF patients with LVEF below 50% and lower serum BDNF concentration present more advanced cardiac remodeling and dysfunction than individuals with higher BDNF. Potential mechanisms and clinical consequences of these findings require further investigation.

Topics: Aged; Brain-Derived Neurotrophic Factor; Heart Failure; Heart Failure, Systolic; Humans; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

The clinically investigated rationale for neprilysin (NEP)-inhibition by angiotensinreceptor-NEPinhibitor (ARNi) therapy is to induce elevations in endogenous natriuretic peptides. NEP, however, cleaves a broad spectrum of substrates, which partially hold significant implications in heart failure with reduced ejection fraction (HFrEF). The effect of NEP inhibition on these peptides has not been investigated thoroughly. This study explored the response of adrenomedullin (ADM) regulation to the initiation of ARNi.. Seventy-four patients with stable HFrEF and initiation of ARNi were prospectively enrolled, 67 patients on continuous angiotensin-converting-enzyme inhibitor(ACEi)/angiotensin-receptor blocker (ARB) therapy served as control. Plasma bioactive-ADM (bio-ADM), mid-regional-pro-ADM (MR-proADM), B-typenatriuretic peptide (BNP) and N-terminal-pro-BNP (NT-proBNP) were determined at baseline, short-term, 1-year and 2-year follow up.. Following ARNi initiation both bio-ADM and MR-proADM concentrations were significantly increased at early and long-term follow up (bio-ADM [pg/mL]: 26.0 [interquartile range {IQR}: 17.7-37.5] vs. 50.8 [IQR: 36.5-78.1] vs. 54.6 [IQR: 42.0-97.1] vs. 57.4 [IQR: 48.5-161.6]; MR-proADM [nmol/L]: 0.87 [IQR: 0.64-1.12] vs. 1.25 [IQR: 0.93-1.79] vs. 1.42 [IQR: 0.95-1.90] vs. 1.60 [IQR: 1.12-2.46], P < .0001 for all). The ratios bio-ADM/MR-proADM and BNP/NT-proBNP increased during ARNi-therapy proving improved availability of bioactive peptides. The proportional increase of bio-ADM markedly exceeded BNP increase. Patients converted to ARNi showed similar biomarker patterns irrespective of baseline renin-angiotensin system blocker therapy, i.e. ACEi or ARB (P > .05 for all), indicating that activation of the ADM-axis arises particularly from NEPinhibition.. The significant increase of MR-proADM and bio-ADM together with an elevated bioADM/MR-proADM ratio suggest both enhanced formation and reduced breakdown of bioactive ADM following the initiation of ARNi. Activation of the ADM-axis represents a so far unrecognized effect of ARNi.

Topics: Adrenomedullin; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Biomarkers; Heart Failure; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Receptors, Angiotensin; Stroke Volume

Fluid overload is a common complication in patients with cirrhosis. B-type natriuretic peptide (BNP) is a marker of increased blood volume, commonly used in heart failure, that has been shown to be elevated in patients with liver disease. This study examined if BNP levels can be used to determine prognosis and predict worsening of ascites in patients with cirrhosis without concomitant heart disease. A retrospective study was performed at a large urban hospital in Chicago, Illinois and included 430 patients with cirrhosis who had BNP levels ordered during their hospital stay. Patients with clinical heart failure, arrhythmias or pulmonary hypertension were excluded. The primary outcome was 90-day mortality and the secondary outcome was a requirement for therapeutic paracentesis in the 90 days following BNP results. 53 patients (12%) had BNP levels ≥ 300 pg/mL. They had significantly increased serum levels of creatinine, bilirubin, and International Normalized Ratio (INR) when compared to those with BNP < 300 pg/mL. Patients with higher BNP had significantly higher mortality rates (HR 3.49; p = 0.037) and were more likely to require therapeutic paracentesis (HR 2.26; p = 0.02) in the next 90 days. A BNP ≥ 300 pg/mL had specificity of 88.2% in predicting 90-day mortality. BNP may serve as a practical and reliable marker of underlying disease severity in patients with cirrhosis, with potential to be included in prognostication tools for assessment of end-stage liver disease.

Topics: Adult; Aged; Area Under Curve; Bilirubin; Biomarkers; Creatinine; Heart Failure, Systolic; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Liver Cirrhosis; Middle Aged; Natriuretic Peptide, Brain; Paracentesis; Proportional Hazards Models; Retrospective Studies; ROC Curve; Severity of Illness Index

B-type natriuretic peptides (BNPs) and their biologically inactive N-terminal parts, namely, NT-proBNPs, are used for diagnostic and prognostic purposes in patients with chronic heart failure (CHF). Associations of BNPs and NT-proBNPs with emotional factors may exist. As depressive and anxious comorbidities and decreases in quality of life (QoL) are common in CHF patients, we explored the associations between NT-proBNP and depression, anxiety, and QoL in patients with CHF using cross-sectional and longitudinal analyses.. We used baseline and one-year follow-up NT-proBNP measurements and sociodemographic and clinical data from 180 patients with systolic CHF from a case management study. Depression was assessed with the Patient Health Questionnaire 9 (PHQ-9), anxiety was assessed with the Generalized Anxiety Disorder Scale 7 (GAD-7), and QoL was determined using the Short Form 36 (SF-36) health survey.. Univariate correlation analyses showed significant negative associations between NT-proBNP and the scores of four out of eight QoL domains (range: r = -0.159 to -0.285, p = .042 to 0.001) of the SF-36 but not between NT-proBNP and depression and anxiety scores. In cross-sectional and longitudinal multivariate regression analyses, no significant associations between NT-proBNP and psychometric variables were found.. In patients with stable, chronic systolic heart failure, only weak relations between NT-proBNP and QoL exist, but no relations between NT-proBNP and depression and anxiety were found. These findings are placed in the current research context of this topic. Implications for future experimental studies are discussed.

Topics: Aged; Anxiety; Comorbidity; Cross-Sectional Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Quality of Life

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

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

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Disease Progression; Female; Heart Failure, Systolic; Humans; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Neopterin; Patient Admission; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Up-Regulation; Ventricular Function, Left

Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-β cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m. A total of 358 patients with stable systolic HF were followed for a median of 1121 (interquartile range, 379-2600) days. Comprehensive evaluation including B-type natriuretic peptide (BNP) and GDF-15 testing was performed at study entry; the analysis was stratified according to kidney function.. Patients with CKD (33.8%) were older, had more often diabetes, and were less often treated with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). GDF-15 was associated with estimated glomerular filtration rate, whereas BNP was associated with left ventricular-end diastolic diameter and ejection fraction (P < 0.01). During follow-up, 244 patients (68.2%) experienced an adverse outcome (death, urgent transplantation, implantation of mechanical circulatory support). In patients with HF and CKD, the Cox proportional hazard model identified BNP, GDF-15, sex, systolic blood pressure, sodium, total cholesterol, and ACEi/ARB treatment as significant variables associated with an adverse outcome (P < 0.05). In multivariable analysis, BNP was replaced by GDF-15. Net reclassification improvement confirmed prognostic superiority of the model encompassing GDF-15 (GDF-15, sodium, total cholesterol, ACEi/ARB treatment) compared with the model without GDF-15 (BNP, sex, sodium, ACEi/ARB treatment), net reclassification improvement 0.62, P = 0.005. In contrast, in patients with HF and normal kidney function, BNP remained superior to GDF-15 in a multivariable model.. In patients with systolic HF and CKD, GDF-15 is more strongly associated with adverse outcomes than the conventionally used BNP.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Pressure; Cholesterol; Female; Follow-Up Studies; Glomerular Filtration Rate; Growth Differentiation Factor 15; Heart Failure, Systolic; Heart Transplantation; Heart-Assist Devices; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Renal Insufficiency, Chronic; Sex Factors; Sodium; Systole

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

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

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

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

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

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

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

Topics: Aged; Aged, 80 and over; Blood Proteins; Female; Galectin 3; Galectins; Gene Expression Regulation; Heart Failure, Systolic; Humans; Hypertrophy, Left Ventricular; Male; MicroRNAs; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

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

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

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

Excessive activated proinflammatory cytokines may promote extracellular matrix alterations which induce adverse left ventricular remodeling in systolic heart failure (SHF). We sought to identify whether high-sensitivity C-reactive protein (hsCRP) levels were independently associated with SHF.. In our retrospective case-control study, 2236 subjects were included, and 260 patients had SHF. Blood sample collection, clinical laboratory tests, electrocardiogram and echocardiography examinations were performed. The questionnaires were completed by professional interviews.. In 2236 subjects, the prevalence rate of SHF were 1.7, 1.8, 8.4 and 32.6% between hsCRP concentrations (<1 mg/L, ≥1 to <3 mg/L, ≥3 to <10 mg/L and ≥10 mg/L, respectively) (p=0.000). hsCRP concentrations (<1 mg/L, ≥1 to <3 mg/L, ≥3 to <10 mg/L and ≥10 mg/L) were associated in a linear trend with N-terminal pro-brain natriuretic peptide (NT-proBNP, p=0.000) and left ventricular ejection fraction (LVEF, p=0.000). hsCRP was also significantly related to NT-proBNP, LVEF and SHF (r=0.232, p=0.000; r=-0.358, p=0.000 and r=0.413, p=0.000, respectively). In logistic regression model, after adjusting for heart failure risk factors, compared with the low concentration of hsCRP (<1 mg/L), the high concentration of hsCRP (≥10 mg/L) was significantly independently associated with SHF (odds ratio = 10.78 [1.303 to 89.10], p=0.027).. Low to high concentration of hsCRP showed a linear trend association with SHF. A high concentration of hsCRP was independently associated with SHF.

Topics: Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Case-Control Studies; Cholesterol; Echocardiography; Electrocardiography; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Retrospective Studies; Risk Factors; Stroke Volume; Ventricular Function, Left

Urocortin 1 (UCN1) has vasodilator, diuretic, and natriuretic effects, and its expression increases in heart failure (HF). Adrenomedullin (ADM) increases cardiac output and lowers blood pressure in healthy men and in patients with heart failure. The aim of the study was to determine UCN1 and ADM levels in patients with HF, to evaluate the relationship of UCN1 and ADM with various clinical parameters, and to assess UCN1 and ADM as diagnostic markers in HF, in comparison with pro-brain natriuretic peptide (pro-BNP).. We investigated serum levels of UCN1, ADM, and pro BNP in 86 consecutive patients with systolic HF [ejection fraction (EF) ≤45%] and 85 healthy controls. Serum UCN1, ADM, and pro-BNP levels were measured with the ELISA method. Transthoracic echocardiography was performed to determine left ventricular EF and pulmonary artery systolic pressure.. UCN1 and ADM levels were higher in HF patients (446.2±145.7 pg/mL, p<0.001; 87.9±4.2 pg/mL, p<0.001 respectively). UCN1 was positively correlated with pro-BNP (r=0.963, p<0.001), ADM (r=0.915, p<0.001), and NYHA (r=0.879, p<0.001); ADM was positively correlated with pro-BNP (r=0.956, p<0.001) and NYHA (r=0.944, p<0.001). Receiver operating characteristic curves yielded an area under the curve of 1.00 (p<0.001) for UCN1, 1.00 (p<0.001) for ADM, and 0.99 (p<0.001) for pro-BNP in the diagnosis of HF.. UCN1 and ADM increase with worsening HF and left ventricular dysfunction. They may be used as diagnostic biomarkers in systolic HF, but the incremental value of measuring UCN1 and ADM in patients tested for pro-BNP is questionable.

Topics: Adrenomedullin; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Echocardiography; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Urocortins

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) appears to be involved in atherosclerotic plaque vulnerability and rupture. In this study, we aimed to evaluate the utility of serum LOX-1 levels in the diagnosis and assessment of left ventricular systolic HF and LOX-1’s relationship with serum pro-brain natriuretic peptide (NT-proBNP).. This was a cross-sectional study of all eligible patients admitted to the department of cardiology of the University Hospital between July 2011 and April 2012.. Fifty-five patients with a diagnosis of systolic heart failure and 25 patients without systolic HF were enrolled in this study. Serum C-reactive protein, NT-proBNP, and LOX-1 were studied.. Serum LOX-1 and NT-proBNP levels were significantly higher in the heart failure group and showed a positive correlation with NT-proBNP and negative correlations with left ventricular ejection fraction (EF). In addition, LOX-1 levels in patients with ischaemic cardiomyopathy were significantly higher, while they were similar in patients with dilated cardiomyopathy compared to control subjects.. Our study demonstrates the utility of the serum LOX-1 levels in the diagnosis of left ventricular systolic heart failure. LOX-1 may have a place in the diagnosis of heart failure, in particular in patients with ischaemic cardiomyopathy.

Topics: Aged; Cross-Sectional Studies; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results; Scavenger Receptors, Class E; Statistics as Topic; Stroke Volume; Turkey; Ventricular Dysfunction, Left

Topics: Biomarkers; Cause of Death; Global Health; Heart Failure, Systolic; Humans; Hydrocortisone; Natriuretic Peptide, Brain; Peptide Fragments; Saliva; Survival Rate

Melanoma cell adhesion molecule (MCAM) is a marker of endothelial damage. MCAM diagnostic and prognostic value was assessed in chronic heart failure (CHF).. 130 CHF patients and 32 controls were included in the study. Telephone follow-up lasted one year. End points were: death from all causes, and hospitalization with CHF exacerbation.. MCAM was higher in patients than in controls (p = 0.01). Receiver operator curve analysis revealed that MCAM may serve as a predictor of death (area under the curve: 0.8404; p < 0.002). Patients with MCAM above 500 ng/ml had worse prognosis (p = 0.03). NT-proBNP and age were independent predictors of death in multivariate analysis.. The increased MCAM indicates endothelial damage in CHF and may serve as a marker of worse prognosis in these patients.

Topics: Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Case-Control Studies; CD146 Antigen; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; ROC Curve; Sensitivity and Specificity

This study shows the impact of secondary mitral regurgitation (sMR) and transcatheter mitral valve repair (TMVR) with the MitraClip system on sympathetic nerve activity (SNA).. An increase in SNA is associated with worse outcomes and limited survival in patients with chronic heart failure (CHF).. Twenty CHF-patients without relevant sMR and 30 CHF patients with symptomatic sMR were enrolled prospectively. All patients underwent standardized laboratory testing and microneurography. Sixteen patients from the sMR group underwent the MitraClip procedure; 10 patients after TMVR and 9 untreated sMR patients completed 6 months of follow-up.. Comparing groups according to presence of sMR, we found no differences in left ventricular dimensions, and serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and noradrenaline; sMR was associated with increased MSNA (106 ± 60 burst/min vs. 74 ± 48 burst/min, d = 0.58), an impaired sympathetic baroreflex gain (10 ± 7 burst/mm Hg vs. 5 ± 5 burst/mm Hg, d = 0.61), and a higher heart rate (90 ± 27/beats/min vs. 78 ± 12/beats/min, d = 0.58). TMVR led to improved New York Heart Association functional class (d > 0.05), reduced levels of NT-proBNP (5,251 ± 3,760 pg/ml vs. 3,710 ± 2,464 pg/ml; d = 0.58) improvement in 6-minute walk test (204 ± 33 m vs. 288 ± 45 m, d = 0.64), but unchanged levels of noradrenaline. TMVR decreased MSNA burst-frequency (130 ± 78 bursts/min vs. 74 ± 21 bursts/min; d = 0.58) and baroreflex gain (7 ± 4 burst/mm Hg vs. 4 ± 1 burst/mm Hg; d = 0.61).. In patients with CHF, concomitant sMR is associated with increased sympathetic nerve activity, which was independent from measured levels of NT-proBNP, noradrenaline, and left ventricular dimensions. Reduction of sMR with the MitraClip procedure reduced SNA and improved baroreflex gain, in line with improvements of functional capacity.

Topics: Aged; Aged, 80 and over; Baroreflex; Biomarkers; Cardiac Catheterization; Case-Control Studies; Exercise Tolerance; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Neurologic Examination; Norepinephrine; Peptide Fragments; Prospective Studies; Recovery of Function; Sympathetic Nervous System; Time Factors; Treatment Outcome; Ventricular Function, Left; Walk Test

B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up.. In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%). Propensity score, matching several confounding baseline variables, was used to match pairs based on treatment strategy. The median follow-up was 37.4months. After propensity matching, a lower incidence of death (HR 0.45, 95%CI: 0.30-0.67, p<0.0001), and death or worsening renal function (HR 0.49, 95%CI 0.36-0.67, p<0.0001) was apparent in echo-BNP-guided group compared to clinically-guided group. Worsening of renal function (≥0.3mg/dl increase in serum creatinine) was observed in 9.8% of echo-BNP-guided group and in 21.4% of clinical assessed group (p<0.0001). The daily dose of loop diuretics did not change in echo-BNP-guided group, while it increased in 65% of patients in clinically-guided group (p<0.0001).. Echo and BNP guided management may improve the outcome and reduce worsening of renal function in outpatients with chronic HFrEF.

Topics: Aged; Cardiovascular Agents; Diuretics; Drug Monitoring; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Italy; Kidney Function Tests; Male; Medication Therapy Management; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Treatment Outcome

Heart failure is becoming more and more important because of an increasing prevalence in elderly people. Even in healthy elderly individuals there are physiological changes in the cardiovascular system which can be modified by cardiac risk factors and comorbidities and trigger the onset of heart failure. The symptoms in the elderly are often atypical and can be difficult to diagnose in the presence of comorbidities. Echocardiography is important for the diagnosis of heart failure and can be easily and non-invasively performed. This can be complemented by further imaging methods and serological tests, such as determination of the concentrations of brain natriuretic peptide (BNP) and n-terminal pro-brain natriuretic peptide (NTproBNP). In elderly patients the problem of polypharmacy often arises. Therapeutic goals are in particular improvement in the quality of life and of symptoms.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiotonic Agents; Echocardiography; Female; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain; Polypharmacy; Ventricular Dysfunction, Left

Both inferior vena cava (IVC) diameter and the degree of inspiratory collapse are used in the estimation of right atrial pressure.. The purpose of this study is to evaluate the utility of IVC diameter, using echocardiography as a marker of volume overload and the relationship between these parameters and N-terminal pro-B natriuretic peptide (NT-proBNP) in patients with systolic heart failure (HF).. We included 136 consecutive patients with systolic HF (left ventricular ejection fraction, <50%), including 80 patients with acutely decompensated HF and 56 patients with compensated HF as well as 50 subjects without a diagnosis of HF. All patients underwent transthoracic echocardiography to assess both their IVC diameters and the degree of inspiratory collapse (≥50%, <50%, and no change [absence] groups); NT-proBNP levels were measured, and these data were compared between the 2 groups.. Inferior vena cava diameter and NT-proBNP were significantly higher among the patients with HF than among the control subjects (21.7 ± 2.6 vs 14.5 ± 1.6 mm, P < .001 and 4789 [330-35000] vs 171 [21-476], P < .001). The mean IVC diameter was higher among the patients with decompensated HF than among the patients with compensated HF (23.2 ± 2.1 vs 19.7 ± 1.9 mm, P < .001). The values of NT-proBNP were associated with different collapsibility of IVC subgroups among HF patients. The NT-proBNP levels were 2760 (330-27336), 5400 (665-27210), and 16806 (1786-35000), regarding the collapsibility of the IVC subgroups: greater than or equal to 50%, less than 50%, and absence groups, P < .001, respectively, among HF patients. There was a significant positive correlation between IVC diameter and NT-proBNP (r = 0.884, P < .001). A cut off value of an IVC diameter greater than or equal to 20.5 mm predicted a diagnosis of compensated HF with a sensitivity of 90% and a specificity of 73%.. Inferior vena cava diameter correlated significantly with NT-proBNP in patients with HF. Inferior vena cava diameter may be a useful variable in determining a patient's volume status in the setting of HF and may also enable clinicians to distinguish patients with decompensated HF from those with compensated HF.

Topics: Biomarkers; Echocardiography; Female; Heart Failure, Systolic; Humans; Inhalation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Vena Cava, Inferior

Limited data exists regarding biomarker use to predict left ventricular (LV) reverse remodeling (R2). Our aim was to examine the value of soluble ST2 (ST2), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and galectin-3 relative to LV-R2 in systolic heart failure (HF), and to develop a clinical score for LV-R2 prediction.. R2 was defined as a) LV ejection fraction (LVEF) increase ≥15%, or b) LVEF increase ≥10% plus reduction of LV end-systolic diameter index ≥20% or LV end-systolic volume ≥40%, for 12 months.. We studied 304 patients (79.6% men, mean age 66.1 ± 12.3 years) with baseline LVEF <40%. R2 was observed in 104 patients (34.2%). In univariable logistic regression, factors associated with R2 were age (p=0.02), non-ischemic etiology of HF (p<0.001), NYHA functional class (p=0.02), baseline LVEF (p=0.005), absence of left bundle branch block (LBBB; p=0.002), ST2 (p=0.004), NT-proBNP (p=0.005), and hs-cTnT (p<0.001); HF duration achieved borderline significance (p=0.08). In multivariable analysis, ST2 remained the only biomarker associated with LV-R2. We developed the ST2-R2 score for use in clinical practice for predicting R2; variables included were ST2 <48 ng/mL, non-ischemic etiology, absence of LBBB, HF duration <12 months, baseline LVEF <24%, and β-blocker treatment. The score had an area under the curve of 0.79 in the derivation cohort and 0.73 in a separate validation cohort.. The ST2-R2 score, which includes the novel biomarker ST2 and five clinical variables, reasonably predicts LV-R2 in systolic HF patients. ST2 was the only studied biomarker that was independently associated with R2.

Topics: Aged; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Galectin 3; Heart Failure, Systolic; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Receptors, Cell Surface; Severity of Illness Index; Stroke Volume; Ventricular Remodeling

Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked.. To identify the prevalence of ID in a HF clinic and evaluate whether ID is associated with increased plasma concentrations of different cardiovascular biomarkers that carry a poor prognosis.. We prospectively included 149 patients with systolic HF referred to an outpatients HF clinic. ID was defined as ferritin<100 μg/L or ferritin 100-300 μg/L and Tranferin-saturation<0.20. Five different cardiovascular biomarkers were analyzed on frozen plasma.. The patients had a median age of 70 (Interquartile range: 64-75) years, 25% were females, 29% were in functional class III-IV and LVEF was 32 (27-39) %. The prevalence of ID was 45% (95%-confidence interval (CI): 37-53%). In multivariate analyses, ID was not associated with plasma concentrations of troponin I, NT-proBNP, MR-proANP, chromogranin A or copeptin (P>0.05 for all) but with plasma concentrations of hs-CRP (odds ratio: 2.03, 95%-CI: 1.02-4.02, P=0.043).. ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF patients.

Topics: Aged; Biomarkers; C-Reactive Protein; Chromogranin A; Comorbidity; Denmark; Female; Ferritins; Glycopeptides; Heart Failure, Systolic; Humans; Iron; Iron Deficiencies; Iron Metabolism Disorders; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prevalence; Prognosis; Statistics as Topic; Transferrin; Troponin I

Adipose tissue has endocrine properties, secreting a wide range of mediators into the circulation, including factors involved in cardiovascular disease. However, little is known about the potential role of adipose tissue in heart failure (HF), and the aim of this study was to investigate epicardial (EAT) and subcutaneous (SAT) adipose tissue in HF patients.. Thirty patients with systolic HF and 30 patients with normal systolic function undergoing thoracic surgery were included in the study. Plasma was sampled and examined with the use of enzyme-linked immunosorbent assays, whereas SAT and EAT biopsies were collected and examined by means of reverse-transcription polymerase chain reaction and gas chromatography. Significantly higher expressions of mRNA encoding interleukin-6, adrenomedullin, peroxisome proliferator-activated receptor α, and fatty acid (FA)-binding protein 3, as well as higher levels of monounsaturated FA and palmitoleic acid, were seen in the EAT of HF patients, whereas the levels of docosahexaenoic acid were lower. Palmitoleic acid levels in EAT were correlated with 2 parameters of cardiac remodeling: increasing left ventricular end-diastolic diameter and N-terminal pro-B-type natriuretic peptide.. Our results demonstrate adipose tissue depot-specific alterations of synthesis of FA and inflammatory and metabolic mediators in systolic HF patients. EAT may be a source of increased circulatory and myocardial levels of these mediators through endocrine actions.

Topics: Adipose Tissue; Adult; Aged; Biomarkers; C-Reactive Protein; Cardiac Surgical Procedures; Case-Control Studies; Chi-Square Distribution; Elective Surgical Procedures; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Female; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pericardium; Real-Time Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric; Subcutaneous Fat; Ultrasonography

Osteoprotegerin (OPG) may predict progression of chronic congestive heart failure (CHF) with increased mortality and play an important role in the development of pulmonary arterial hypertension (PAH). Mounting evidence suggests that PAH developed during CHF is not solely caused by a "passive" increase from the left ventricular enddiastolic pressure, but rather a "reactive" response from contributing lung endothelial dysfunction and vascular remodelling, a pathological process that can be significantly influenced by endothelial progenitor cells (EPCs).This study aims to examine whether circulating EPCs from patients with CHF are affected and if OPG could be implicated during disease progression.. In this study EPCs were isolated, cultured, and quantified from patients of CHF with (n = 20) or without PAH (n=40) as measured by right heart catheterization. Serum levels of OPG and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were analysed and correlated with EPCs.. A significant decrease in circulating EPCs (39.3 ?9.1 vs 67.1 ?10.5 EPCs/x200 field; P <0.05) was found in CHF patients who developed PAH compared to those without PAH. Both OPG (551.90 +/- 49.83 vs. 312.29 +/- 31.12 pg/ml; P<0.05) and NT-pro BNP (2,946.50 +/- 1,434.50 vs. 1,328.20 +/- 811.90; P < 0.05) were also significantly elevated in CHF patients with PA H. Circulating level of OPG correlated inversely with EPCs (r = -0.45, P = 0.037) but positively with mPAP (r =0.53, P=0.011).. Our study demonstrates that OPG elevation and EPC depletion are associated with CHF patients who have developed PAH. The inverse relationship of circulating OPG with EPCs suggests a possible mechanism for OPG in the development of pulmonary vascular dysfunction, thus worsening prognosis for CHF patients.

Topics: Adult; Cells, Cultured; Disease Progression; Echocardiography, Doppler, Color; Endothelial Progenitor Cells; Endothelium, Vascular; Female; Heart Failure, Systolic; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Prognosis

It is unclear whether adaptive servo-ventilation (ASV) is safe and effective in patients with severe systolic heart failure (HF). Our aim in this study was to estimate the safety and efficacy of ASV therapy for patients with severe systolic HF.. Seventy-six HF patients (age: 69±12 years; 53 men), categorized as New York Heart Association (NYHA) Class II-IV, with left ventricular ejection fraction (LVEF) of <50%, received ASV therapy after optimal medical therapy to determine the safety and efficacy of ASV. Patients were divided into 2 groups based on their LVEF: group L (LVEF<30%; n=42) and group H (LVEF≥30%; n=34). After 6 months of ASV therapy, we compared the changes in LVEF, brain natriuretic peptide (BNP), and incidence of fatal cardiovascular events between the groups.. The groups differed significantly with respect to beta-blocker treatment before ASV therapy (p<0.0001). After 6 months of ASV therapy, LVEF and BNP levels had improved in both groups. In group L, LVEF had improved from 24.1±5.6% to 35.2±10.6% (p<0.0001) and BNP from 591 (273-993)pg/ml to 142 (39-325)pg/ml (p=0.002). Moreover, 1-year follow-up data showed a tendency toward improvement of NYHA classification in group L (group L: 50%; group H: 29%; p=0.07), and showed no significant difference with regard to fatal cardiovascular events between the 2 groups (group L: 11.9%; group H: 5.9%; p=0.36).. Our study demonstrated that ASV therapy is safe and effective for use in very severe systolic HF patients as well as in relatively mild systolic HF patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Female; Heart Failure; Heart Failure, Systolic; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Respiration, Artificial; Safety; Severity of Illness Index; Stroke Volume; Time Factors; Treatment Outcome

Urocortin 1 (UCN1) has cardiostimulatory, vasodilatory, diuretic and natriuretic effects, and its expression increases in heart failure (HF).. To determine UCN1 levels in patients with HF, to evaluate UCN1's relationship with various clinical parameters, and to assess UCN1 as a diagnostic marker in HF, compared to pro-B-type natriuretic peptide (pro-BNP).. We investigated serum levels of UCN1 and pro-BNP in 90 consecutive patients with systolic HF (left ventricular ejection fraction [LVEF] ≤ 45%) and 90 healthy controls. Serum UCN1 and pro-BNP levels were measured using the ELISA method. Transthoracic echocardiography was performed to determine LVEF and pulmonary artery systolic pressure (PASP). Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula.. UCN1 level was higher in HF patients (391.5 [357.0-482.0] pg/mL, p < 0.001). UCN1 was positively related with NYHA class (r = 0.89, p < 0.001), and PASP (r = 0.39, p < 0.001); and negatively related with LVEF (r = -0.46, p < 0.001), and GFR (r = -0.21, p = 0.046). A significant positive correlation was found between pro-BNP and UCN1 levels (p < 0.001, r = 0.96). Receiver operating characteristic (ROC) curves yielded an area under the curve (AUC) of 0.99 (95% CI 0.98-1.00,p < 0.001) for UCN1 and 1.00 (p < 0.001) for pro-BNP in the diagnosis of HF.. UCN1 increases with worsening HF and left ventricular dysfunction. It may be used as a diagnostic biomarker in systolic HF, but the incremental value of measuring UCN1 in patients tested for pro-BNP is questionable.

Topics: Adult; Case-Control Studies; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Systole; Urocortins; Ventricular Function, Left

In patients with acute decompensated systolic heart failure (ADSHF) high resting heart rate (HR) could be either a compensatory mechanism or contribute to worsening heart failure. The aim of this study was to evaluate, in patients with ADSHF and resting HR >70 bpm, the early (within 24 h) and late (at discharge) effects of oral administration of ivabradine on HR reduction.. Ten consecutive patients with ADSHF, left ventricular ejection fraction <40 % and HR >70 bpm, without other acute conditions or inotropic therapy, began open-label treatment with oral ivabradine according to a pre-established Heart Failure Unit protocol. We obtained clinical and laboratory data at four periods: admission (T0), immediately before initiation of ivabradine (T2), 24 h after initiation of ivabradine (T3), and at discharge (T4).. Ivabradine was administered in 60 % of the patients before the second day. HR decreased 10.7 ± 7.2 bpm at T3 (p < 0.001) and 16.3 ± 8.2 bpm at T4 (p = 0.002). The systolic blood pressure decreased at T3 (p = 0.012), returning to baseline values at T4. There was no change in diastolic and mean blood pressure. New York Heart Association (NYHA) class improvement by two levels was associated with lower HR at T4 (p = 0.033). HR and N-terminal pro-brain natriuretic peptide (Nt-ProBNP) at baseline correlated significantly [Spearman correlation coefficient (rs) = 0.789, p = 0.013]. Total Nt-ProBNP reduction correlated with the HR before (r = 0.762, p = 0.028) and after (T3: r = 0.647, p = 0.083; T4: r = 0.738, p = 0.037) ivabradine addition.. In the present cohort of patients with ADSHF and HR >70 bpm, the selective reduction of HR with oral ivabradine was safe and efficient.

Topics: Acute Disease; Aged; Aged, 80 and over; Benzazepines; Blood Pressure; Female; Heart Failure, Systolic; Heart Rate; Humans; Intensive Care Units; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors

To evaluate the long-term predictive value of serial Nt-ProBNP during dry-state in patients with systolic heart failure (SHF).. Nt-ProBNP was measured quarterly during a 6-month dry-state period in 40 SHF outpatients. EVENTS: all-cause mortality or hospitalization.. 5 years.. The Nt-ProBNP >1000 pg/ml (baseline and 6 months) and the variation rate (VR) >30% were independently associated with the survival and composite endpoint curve. VR >30% added significant prognostic information to the single Nt-ProBNP 1000 pg/ml cut-off. Patients with at least one Nt-ProBNP determination >1000 pg/ml were at greater risk of death.. Serial Nt-ProBNP measurements in patients with SHF during the dry-state are strong predictors of the long-term prognosis.

Topics: Aged; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

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

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

Topics: Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Lung; Male; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Pulmonary Edema

Topics: Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Lung; Male; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Pulmonary Edema

Topics: Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Lung; Male; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Pulmonary Edema

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

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

Galectin-3 (Gal-3) shows the ability of survival prediction in heart failure (HF) patients. However, Gal-3 is strongly associated with serum markers of cardiac extracellular matrix (ECM) turnover. The aim of this study is to compare the impact of Gal-3 and serum markers of cardiac ECM turnover on prognostic prediction of chronic systolic HF patients.. Serum Gal-3, brain natriuretic peptide (BNP), extracellular matrix including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2, 9 (MMP-2, 9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. Cox regression analysis was used for survival analysis.. A total of 105 (81 male) patients were enrolled. During 980±346 days follow-up, 17 patients died and 36 episodes of HF admission happened. Mortality of these patients was significantly associated with the log PIIINP (β= 15.380; P=0.042), log TIMP-1(β= 44.530; P=0.003), log MMP-2 (β= 554.336; P<0.001), log BNP (β= 28.273; P=0.034). Log Gal-3 (β= 7.484; P=0.066) is borderline associated with mortality. Mortality or first HF admission of these patients was significantly associated with the log TIMP-1(β= 16.496; P=0.006), log MMP-2 (β= 221.864; P<0.001), log BNP (β= 5.999; P=0.034). Log Gal-3 (β= 4.486; P=0.095) only showed borderline significance. In several models adjusting clinical parameters, log MMP-2 was significantly associated with clinical outcome. In contrast, log Gal-3 was not.. The prognostic strength of MMP-2 to clinical outcome prediction in HF patients is stronger than Gal-3.

Topics: Aged; Female; Galectin 3; Heart Failure, Systolic; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Procollagen; Tissue Inhibitor of Metalloproteinase-1

Inflammation and dystrophic calcification have been associated with cardiovascular disease (CVD) and chronic heart failure (CHF). The aim of the present study was to investigate the potential usefulness of fetuin-A as a biomarker in CHF.. Serum fetuin-A was measured in 66 CHF patients with left ventricular function < 50% and in 31 healthy controls at baseline. Fetuin-A was evaluated as a diagnostic marker for systolic heart failure and compared with C-reactive protein (CRP) and pro-brain natriuretic peptide (pro-BNP).. The levels of serum fetuin-A were significantly decreased in the CHF patients compared to the control group (P < 0.01). Although there were significant correlations between fetuin-A and certain parameters in patients and controls, none of these were present consistently in either group. It was found that serum fetuin-A levels could identify patients with systolic heart failure with a high degree of sensitivity and specificity.. Serum fetuin-A is decreased in CHF patients, indicating that anti-inflammatory activity is downregulated in CHF and that calcification may be associated with CHF.

Topics: Aged; alpha-2-HS-Glycoprotein; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left

Cardiac transplantation represents the best procedure to improve long-term clinical outcome in advanced chronic heart failure (CHF), if pre-selection criteria are sufficient to outweigh the risk of the failing heart over the risk of transplantation. Although the cornerstone of success, risk assessment in heart transplant candidates is still under-investigated. Amino terminal pro B-type natriuretic peptide (NT-proBNP) is regarded as the best predictor of outcome in CHF, and the Seattle Heart Failure Score (SHFS), including clinical markers, is widely used if NT-proBNP is unavailable.. The present study assessed the predictive value for all-cause death of the SHFS in CHF patients and compared it with NT-proBNP in a multivariate model including established baseline parameters known to predict survival.. A total of 429 patients receiving stable HF-specific pharmacotherapy were included and monitored for 53.4 ± 20.6 months. Of these, 133 patients (31%) died during follow-up. Several established predictors of death on univariate analysis proved significant for the total study cohort. Systolic pulmonary arterial pressure (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05); p < 0.001, Wald 15.1), logNT-proBNP (HR, 1.51; 95% CI, 1.22-1.86; p < 0.001, Wald 14.9), and the SHFS (HR, 0.99; 95% CI, 0.99-1.00; p < 0.001, Wald 12.6) remained within the stepwise multivariate Cox regression model as independent predictors of all-cause death. Receiver operating characteristic curve analysis revealed an area under the curve of 0.802 for logNT-proBNP and 0.762 for the SHFS.. NT-proBNP is a more potent marker to identify patients at the highest risk. If the NT-proBNP measurement is unavailable, the SHFS may serve as an adequate clinical surrogate to predict all-cause death.

Topics: Adult; Aged; Biomarkers; Female; Heart Failure; Heart Failure, Systolic; Heart Transplantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Severity of Illness Index; Washington

The prevalence of malnutrition in ambulatory patients with heart failure is difficult to determine, depending on the timing and methodology.. To determine the nutritional status of outpatients with systolic heart failure with the Mini Nutritional Assessment (MNA) full and short-form versions, and evaluate its relationship with the short-term prognosis, biomarkers and quality of life.. Fifty consecutive (70% male), geriatric (74.3+ 6.2years old) stable outpatient with heart failure (NYHA class II 68%, III 32%) and left ventricular ejection fraction of 26.7 +11.5% were included and followed during 12 months. At a routine visit to the heart failure clinic, the MNA, the Minnesota Living with Heart Failure questionnaire (MLHFQ) were applied. According to the MNA screening score the nutritional status was classified using the MNA full (MNA-F) and the short-form (MNA-F) versions of the questionnaire. The recorded events were death and hospitalization.. The survival and hospitalizations curves were evaluated with the Log-Rank test and Cox Regression analysis. The association between parameters was analyzed with the Pearson and Spearmann correlation coefficient.. (1) The mortality and hospitalization rates were 12% and 42%, respectively. (2) With the MNA-SF 7.6% of the patients had malnutrition and 20% were at risk of malnutrition. There was a good agreement (90%) between the MNA-SF and the MNA-F classifications. (3) There was a significant relationship between the MNA screening score and the MLHFQ (rs= -0.592 p<0.001), Nt-ProBNP (rs= -0.49 p<0.001) and total plasma protein (r= 0.672 p=0.006); (3) The MNA-SF nutritional classification was associated with the 12 months survival (Log-Rank p=0.044) and hospitalization (Log-Rank p=0.005) curves. (4) Those patients with malnutrition by the MNA-SF were at greater risk of death (HR= 8.0 p=0.059) and hospitalization (HR 8.1 p=0.008).. The MNA is useful for the evaluation of the nutritional status of elderly outpatients with systolic heart failure. It is a good predictor of the short-term outcome and is also associated with the quality of life and Nt-ProBNP.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Geriatric Assessment; Geriatrics; Heart Failure, Systolic; Hospitalization; Humans; Male; Malnutrition; Natriuretic Peptide, Brain; Nutrition Assessment; Nutritional Status; Outpatients; Peptide Fragments; Prevalence; Prognosis; Proportional Hazards Models; Quality of Life; Surveys and Questionnaires

Augmented peripheral chemoreflex response is an important mechanism in the pathophysiology of chronic heart failure (CHF). This study characterizes prevalence and clinical predictors of this phenomenon in optimally managed male CHF patients, and seeks to describe the hemodynamic consequences of chemoreceptor hypersensitivity.. Thirty-four optimally managed CHF patients and 16 control subjects were prospectively studied. Hypoxic ventilatory response (HVR)-a measure of peripheral chemosensitivity-was calculated with the use of short nitrogen gas administrations. Systolic blood pressure (SBP) and heart rate (HR) following transient hypoxic challenges were recorded with a Nexfin monitor. Hemodynamic responses to hypoxia were expressed by the linear slopes between oxygen saturation (%) and SBP (mm Hg) or HR (beats/min). Elevated HVR was present in 15 (44%) of the CHF patients. Patients with elevated HVR exhibited higher levels of N-terminal pro-B-type natriuretic peptide, lower left ventricular ejection fraction, and higher prevalence of atrial fibrillation. CHF patients with elevated HVR had significantly greater SBP and HR responses to hypoxia than CHF patients with normal HVR.. Despite comprehensive pharmacotherapy, elevated HVR is prevalent in CHF patients, related to severity of the disease and associated with augmented hemodynamic responses to hypoxia. CHF patients with elevated HVR may be prone to unfavorable hemodynamic changes.

Topics: Atrial Fibrillation; Blood Pressure; Case-Control Studies; Chemoreceptor Cells; Heart Atria; Heart Failure, Systolic; Heart Rate; Heart Ventricles; Humans; Hypoxia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Ultrasonography

Non-ischaemic heart failure is one of the today's most prevalent cardiovascular disorders. Since modern pharmacotherapy has proved to be very effective in delaying disease progression and preventing death, imaging modalities and molecular biomarkers play an important role in early identification and clinical management as well as risk assessment of patients. The present study evaluated for the first time whole peripheral blood miRNAs as novel biomarker candidates for non-ischaemic heart failure with reduced ejection fraction (HF-REF).. We assessed genome-wide miRNA expression profiles in 53 HF-REF patients and 39 controls. We could identify and validate several miRNAs that show altered expression levels in non-ischaemic HF-REF, discriminating cases from controls both as single markers or when combined in a multivariate signature. In addition, we demonstrate that the miRNAs of this signature significantly correlate with disease severity as indicated by left ventricular ejection fraction.. Our data further denote that miRNAs are potential biomarkers for systolic heart failure. Since their detection levels in whole blood are also related to the degree of left ventricular dysfunction, they may serve as objective molecular tools to assess disease severity and prognosis.

Topics: Biomarkers; Case-Control Studies; Female; Genome-Wide Association Study; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Male; MicroRNAs; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Dysfunction, Left

This study sought to examine the relationships between right ventricular (RV) function, body composition, and prognosis in patients with advanced heart failure (HF).. Previous studies investigating HF-related cachexia have not examined the impact of RV function on body composition. We hypothesized that RV dysfunction is linked to weight loss, abnormal body composition, and worsened prognosis in advanced HF.. Subjects with advanced HF (n = 408) underwent prospective assessment of body composition (skinfold thickness, dual-energy X-ray absorptiometry), comprehensive echocardiography, and blood testing. Subjects were followed up for adverse events (defined as death, transplantation, or circulatory assist device).. Subjects with RV dysfunction (51%) had lower body mass index, lower fat mass index, and were more likely to display cachexia (19%). The extent of RV dysfunction correlated with greater antecedent weight loss and a lower fat/lean body mass ratio. Over a median follow-up of 541 days, there were 150 events (37%). Risk of event was greater in subjects with RV dysfunction (hazard ratio: 3.09 [95% confidence interval (CI): 2.18 to 4.45]) and cachexia (hazard ratio: 2.90 [95% CI: 2.00 to 4.12]) in univariate and multivariate analyses. Increased body mass index was associated with a lower event rate (HR per kg/m(2): 0.92 [95% CI: 0.88 to 0.96]), and this protection was mediated by a higher fat mass (0.91 [95% CI: 0.87 to 0.96]) but not a fat-free mass index (0.97 [95% CI: 0.92 to 1.03]).. RV dysfunction and cardiac cachexia often coexist, have additive adverse impact, and might be mechanistically interrelated. Wasting of fat but not of lean mass was predictive of adverse outcome, suggesting that fat loss is either a surrogate of enhanced catabolism or adipose tissue is cardioprotective in the context of HF.

Topics: Adiponectin; Age Factors; Body Composition; Body Fat Distribution; Body Mass Index; Cachexia; Echocardiography; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Rate; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Severity of Illness Index; Ventricular Dysfunction, Right

Heart rate (HR) reduction in patients with systolic heart failure (HF) is a cornerstone of current therapy. The aim of this study was to evaluate the short-term effect of the HR reduction with ivabradine on N-terminal pro-brain natriuretic peptide (NT-proBNP) in outpatients with systolic HF.. Ivabradine improves survival and promotes left ventricle remodelling by reducing resting heart rate. Nt-ProBNP absolute and trends predict prognosis. We hypothesized a possible association between heart rate decrease and Nt-ProBNP values.. We included 25 outpatients with systolic HF on optimized medical therapy (80% on angiotensin-converting enzyme inhibitors, 56% on spironolactone, and 88% on β-blocker therapy), left ventricle ejection fraction <40%, and sinus rhythm and HR >70/bpm. After a 1 month running-out period, to establish the clinical and NT-proBNP stability, patients were started on ivabradine for 3 months.. Ivabradine decreased NT-proBNP (P = 0.002) from a median of 2850 pg/mL to 1802 pg/mL, corresponding to a median absolute and percent decrease of 964 pg/mL and 44.5%, respectively. The baseline HR correlated significantly with the baseline NT-proBNP (rs = 0.411, P = 0.041). The absolute and percent HR decrease correlated with the absolute NT-proBNP decrease (rs = 0.442, P = 0.027; rs = 0.395, P = 0.05). The greater the NT-proBNP absolute decrease tertile, the greater the baseline HR (P = 0.023) and the absolute (P = 0.028) and percent (P = 0.064) HR variation.. In outpatients with systolic HF, the NT-proBNP reduction obtained by short-term ivabradine treatment correlates closely with the degree of HR reduction.

Topics: Aged; Ambulatory Care; Anti-Arrhythmia Agents; Benzazepines; Biomarkers; Drug Therapy, Combination; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Up-Regulation; Ventricular Function, Left

The aim of this study was to define the performance of lung ultrasound (LUS) compared with clinical assessment, natriuretic peptides, and echocardiography, to evaluate decompensation in patients with systolic heart failure (HF) in an outpatient clinic.. Evaluation of pulmonary congestion in chronic HF is challenging. LUS has been recently proposed as a reliable tool for the semiquantification of extravascular lung water through assessment of B-lines.. This was a cohort study of patients with moderate to severe systolic HF. Receiver-operating characteristic (ROC) analyses were performed to compare LUS with a previously validated clinical congestion score (CCS), amino-terminal portion of B-type natriuretic peptide (NT-proBNP), E/e' ratio, chest x-ray, and 6-min walk test.. Ninety-seven patients were enrolled. Decompensation was present in 57.7% of patients when estimated by CCS, 68% by LUS, 53.6% by NT-proBNP, and 65.3% by E/e' ≥15. The number of B-lines was correlated to NT-proBNP (r = 0.72; p < 0.0001), E/e' (r = 0.68; p < 0.0001), and CCS (r = 0.43; p < 0.0001). In ROC analyses, considering as reference for decompensation a combined method (E/e' ≥ 15 and/or NT-proBNP >1,000 pg/ml), LUS yielded a C-statistic of 0.89 (95% confidence interval: 0.82 to 0.96), providing the best accuracy with a cutoff ≥ 15 B-lines (sensitivity 85%, specificity 83%). A systematic approach using CCS, E/e', NT-proBNP, chest x-ray, and 6-min walk test in different combinations as reference for decompensation also corroborated this cutoff and found a similar accuracy for LUS.. In an HF outpatient clinic, B-lines were significantly correlated with more established parameters of decompensation. A B-line ≥15 cutoff could be considered for a quick and reliable assessment of decompensation in outpatients with HF.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Cohort Studies; Echocardiography, Doppler; Exercise Test; Female; Heart Failure, Systolic; Humans; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Edema; ROC Curve

The study objectives were to determine the circulating levels of proBNP1-108, the precursor of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP), in patients with systolic heart failure (HF) and to assess their prognosis value for cardiovascular (CV) death over a long-term follow-up. Seventy-three patients with systolic HF and 68 healthy volunteers were included. ProBNP1-108, BNP and NT-proBNP levels were measured with automated immunoassays and their predictive value for long-term survival was assessed through an 8 years follow-up. ProBNP1-108 levels were markedly increased in patients with systolic HF in comparison to healthy volunteers. In univariate proportional hazard model, survival was related to proBNP1-108, BNP, NT-proBNP, age, EF and glomerular filtration rate (eGFR). Kaplan-Meier survival curves according to proBNP tertiles diverged significantly, and the highest proBNP levels were related to patients with the highest risk of CV death. In a multivariate analysis including age, EF, proBNP1-108, BNP, NT-proBNP, and eGFR levels, NT-proBNP was the strongest predictor of long term CV death. Our study therefore demonstrated that high levels of proBNP1-108, measured with an assay with enhanced analytical specificity, are related to the long-term risk of cardiovascular death in systolic heart failure.

Topics: Age Factors; Aged; Case-Control Studies; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk; Stroke Volume; Survival Analysis

To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF).. It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF.. Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed.. Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m(2) (18-157). A total of 252 patients died. All five biomarkers--log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P<0.001)--were associated with mortality risk, but not affected by RD (P>0.05 for all interactions).. Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Neostigmine; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Factors; Troponin T

Increased arterial stiffness is an indicator of mortality. This study consists of an 18-month follow-up of the mortality in advanced heart failure patients with increased arterial stiffness.. The study followed up 98 patients with a diagnosis of heart failure in NYHA class III and IV (76 males, 22 females and mean age of 60 ± 12 years) with a left ventricular ejection fraction ≤ 35% as determined by the Simpson method. Augmentation index (Aix) and pulse wave propagation velocity (PWV) parameters were used as indicators of arterial stiffness. Aix and PWV values were measured by arteriography.. 36 patients died. Both Aix and PWV were powerful determinants of mortality, independent of other prognostic variables (p = 0.013, OR: 0.805; p = 0.025, OR: 0.853). A cutoff value for Aix of -14.33 gave 91.2%, 80.3% sensitivity and specificity. A cutoff value for PWV of 11.06 gave 82.4%, 65.4% sensitivity and specificity mortality was predicted. Left ventricular ejection fraction (p = 0.008, OR: 0.859) and B-type natriuretic peptide (p = 0.01, OR: 0.833) was the other independent determinant of mortality. A significant difference was found in both Aix and PWV between the compensated measurements and decompensated heart failure measurements made in 70 patients (p = 0.035, p = 0.048).. Measurement of arterial stiffness is a convenient, inexpensive and reliable method for predicting mortality in patients with advanced heart failure.

Topics: Aged; Biomarkers; Chi-Square Distribution; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Prognosis; Pulse Wave Analysis; Reproducibility of Results; Risk Factors; Stroke Volume; Time Factors; Vascular Stiffness; Ventricular Function, Left

The aim of this study was to evaluate, according to functional response, the neuroendocrine and inflammatory status in patients with chronic heart failure before and after therapy with carvedilol.. Serum tumor necrosis factor-α (TNF-α) soluble receptors (sTNF-R1 and sTNF-R2), interleukin (IL)-10 and IL-18, chromogranin A (CgA) and brain natriuretic peptide (pro-BNP) were measured in 37 New York Heart Association class II to IV heart failure patients, at baseline and after 6 months of therapy with carvedilol. Patients were divided in two groups according to whether, following carvedilol, left-ventricular ejection fraction (LVEF) had increased by at least 5% (17 patients) or not (20 patients). Baseline LVEF was higher in nonresponders (38 ± 5 vs. 31 ± 7%, P = 0.002). In responders, LVEF increased from 31 ± 7 to 51 ± 7% (P < 0.0001), whereas in nonresponders it decreased from 38 ± 5 to 33 ± 7%, (P = 0.02). sTNF-R1 (P = 0.019) and sTNF-R2 (P = 0.025) increased in nonresponders, whereas they did not change in responders. After carvedilol, IL-10 was significantly higher in responders (P = 0.03). Conversely, no significant IL-18 and CgA changes were observed in either group. CgA was not significantly different between groups at baseline and after carvedilol in either group, whereas pro-BNP significantly increased in nonresponders (from 438 ± 582 to 1324 ± 1664 pg/ml, P = 0.04) and decreased in responders (from 848 ± 1221 to 420 ± 530 pg/ml, P = 0.08).. Increased inflammatory activation observed only in heart failure patients not improving left-ventricular function after carvedilol may indicate that inflammation, either as a direct cause or as a consequence, is associated with progressive ventricular dysfunction.

Topics: Adrenergic beta-Antagonists; Aged; Carbazoles; Carvedilol; Cohort Studies; Cytokines; Echocardiography; Female; Heart Failure, Systolic; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Quality of Life; Severity of Illness Index; Stroke Volume; Treatment Outcome

Left ventricular hypertrophy (LVH) and systolic dysfunction would predict the mortality of patients undergoing maintenance hemodialysis. The cause of LVH is usually related to the increase of total peripheral vascular resistance and overloading volume. The presence of residual diuresis enables greater control of the volume. This study evaluated the effects of residual renal function (RRF) on the left ventricle and analyzed the related factors involved in hemodialysis patients.. A total of 59 hemodialysis patients were classified into two groups. The patients in the RRF (RRF+) group had a urine volume greater than 200 mL/24 h, and the patients in the non-RRF (RRF-) group had a urine volume less than 200 mL/24 h. B-type natriuretic peptide (BNP), blood total homocysteine (tHcy), and blood biochemical indexes were determined for the patients in both groups. Echocardiography and Doppler tests were performed to determine the cardiac indexes.. LVH and systolic dysfunction in the RRF+ group were less severe than those in the RRF- group. The concentration of tHcy and BNP in patients with RRF was decreased in comparison with those without RRF. The concentration of tHcy and BNP was positively correlated with the residual diuresis.. There were distinct ventricular geometric patterns and different functional performances between RRF+ and RRF- groups. The presence of residual diuresis had a beneficial effect on the left ventricular function in hemodialysis patients.

Topics: Adult; Aged; Blood Chemical Analysis; Blood Pressure Determination; Cohort Studies; Echocardiography, Doppler; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Homocysteine; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Dialysis; Retrospective Studies; Survival Analysis; Treatment Outcome; Urination; Urine

Tricuspid regurgitation (TR) is common in patients with chronic heart failure (CHF) but its prognostic impact is unclear.. A total of 576 consecutive patients with CHF were prospectively included. The impact of moderate and severe (significant) TR on the combined endpoint death/heart transplantation/left ventricular-assist device implantation was assessed. Patients were followed for 5.8 ± 4.2 (maximum 14.4) years. Kaplan-Meier analysis showed a worse outcome of patients with significant TR (P < 0.0001). By multivariable analysis, amino terminal pro B-type natriuretic peptide (NT-proBNP) (P = 0.0028), systolic left ventricular function (LVF) (P = 0.0014), serum sodium, NYHA functional class, systolic blood pressure, right atrial size (all P = 0.0001), but not TR were significantly related with the outcome. However, as soon as the strong interaction between TR and LVF was included in the model, significant TR determined outcome as well (P = 0.0059). Therefore, in a second analysis patients were stratified for LVF. In patients with mildly or moderately impaired LVF, TR was significantly related with the outcome (HR: 1.368, CI: 1.070-1.748, P = 0.0125), whereas in patients with severely depressed LVF it was not (P = 0.1401). As a proof of concept, we additionally stratified patients according to serum NT-proBNP concentrations. In patients with NT-proBNP concentrations below the median (≤ 280 fmol/mL), TR was related with the outcome (HR: 2.512, CI: 1.127-5.597, P = 0.0242) but it was not in patients with NT-proBNP concentrations above the median (P = 0.3935).. The prognostic impact of TR depends on the severity of CHF. While TR was significantly related with excess mortality in mild to moderate CHF, it provided no additive value in advanced disease when compared with established risk factors.

Topics: Chronic Disease; Electrocardiography; Female; Heart Failure, Systolic; Heart Transplantation; Heart-Assist Devices; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Tricuspid Valve Insufficiency

In patients with chronic heart failure, physical evaluation and clinical judgment may be inadequate for prognostic stratification.. Information obtained with simple bedside tests would be helpful in patient management.. We report on 142 outpatients with systolic heart failure seen at our heart failure unit from 2007 to 2010 (ages 69.4 ± 8.9 years; ejection fraction [EF] 30.6 ± 6.1%; 43% with implanted defibrillators and/or resynchronization devices). At their first visit, we assessed levels of brain natriuretic peptide (BNP) (pg/mL), evaluated transthoracic conductance (TFC) (1/kΩ) by transthoracic bioimpedance, and performed echocardiography.. Four-year mortality was 21.2%. At multivariate analysis, surviving and deceased subjects did not differ regarding New York Heart Association, age, gender, heart failure etiology, or EF at index visit. Patients who died had higher BNP and TFC (BNP = 884 ± 119 pg/mL vs 334 ± 110 pg/mL; TFC = 50 ± 8/kΩ vs 37 ± 7/kΩ, both P < 0.001]. Patients with BNP < 450 pg/mL and TFC < 40/kΩ had a 2.1% 4-year mortality, compared to 46.5% mortality of patients having BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ. BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ showed high sensitivity (91%) and specificity (88%)in identifying patients who died at follow-up.. The combined use of BNP and impedance cardiography during the first assessment of a patient in a heart failure unit identified those carrying a worse medium-term prognosis. This approach could help the subsequent management of patients, allowing better clinical and therapeutic strategies.

Topics: Aged; Ambulatory Care; Biomarkers; Cardiography, Impedance; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Factors; Stroke Volume; Time Factors; Ventricular Function, Left

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment.. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment.. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Death, Sudden, Cardiac; Deoxyguanosine; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Propanolamines; Prospective Studies; Risk Factors; Treatment Outcome

Despite major advances in our understanding of 'systolic' heart failure, at present the epidemiology, pathophysiology, and therapy of heart failure with preserved left ventricular ejection fraction (HFpEF) is poorly understood, in large part because of the lack of robust and widely accepted diagnostic criteria. Although there is a good evidence base for the treatment of systolic heart failure, similar data are lacking for the treatment of HFpEF. Methods In our study, we will screen a consecutive series of 5000 subjects aged ≥60 from the community. Following symptom questionnaire and echocardiography, metabolic exercise testing will be used to confirm whether or not patients thought clinically to have HFpEF are in fact exercise limited and that this limitation is cardiac in origin. Blood samples for plasma brain natriuretic peptide (BNP) will be taken at rest and following exercise in symptomatic patients and matching controls.. At the end of our study we will establish community prevalence and population characteristics of HFpEF, and also evaluate the diagnostic accuracy of current echocardiography parameters and BNP for the diagnosis of the condition.

Topics: Aged; Aged, 80 and over; Echocardiography, Doppler; Exercise Test; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Prevalence; Stroke Volume; United Kingdom; Ventricular Dysfunction, Left; Ventricular Function, Left

Diagnosis and risk stratification of patients with heart failure remain a challenge. The small non-coding RNAs known as microRNAs regulate gene expression and seem to play an important role in the pathogenesis of heart failure. In the current study, we aim to characterize the levels of microRNAs in the sera of chronic systolic heart failure patients vs. controls and assess the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in heart failure patients.. The levels of 186 microRNAs were measured in the sera of 30 stable chronic systolic heart failure patients and 30 controls using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The differences in microRNA levels between the two groups were characterized, and a score, based on the levels of four specific microRNAs with the most significant increase in the heart failure group (miR-423-5p, miR-320a, miR-22, and miR-92b), was defined. The score was used to discriminate heart failure patients from controls with a sensitivity and specificity of 90%. Moreover, in the heart failure group, there was a significant association between the score and important clinical prognostic parameters such as elevated serum natriuretic peptide levels, a wide QRS, and dilatation of the left ventricle and left atrium (r = 0.63, P = 3e-4; P = 0.009; P = 0.03; and P = 0.01, respectively).. Elevated serum levels of specific microRNAs: miR-423-5p, miR-320a, miR-22, and miR-92b, identify systolic heart failure patients and correlate with important clinical prognostic parameters.

Topics: Aged; Chronic Disease; Female; Heart Failure, Systolic; Humans; Male; MicroRNAs; Middle Aged; Natriuretic Peptide, Brain; Prognosis

We aimed to identify whether N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) at peak exercise can provide incremental clinical information over resting levels. A total of 90 patients with systolic heart failure were prospectively studied. Levels of plasma NT-proBNP were assessed at rest and at peak exercise during a cardiopulmonary exercise test. Patients were followed-up for 30 ± 10 months. Levels of NT-proBNP at baseline and peak exercise were significantly correlated with left ventricular ejection fraction ([LVEF] r = -.629, P < .001 and r = -.630, P < .001, respectively) and peak oxygen uptake ([Vo (2)] r = -.752, P < .001 and r = -.740, P < .001, respectively). Levels of plasma NT-proBNP at peak exercise demonstrated similar predictive ability for the detection of patients with low peak Vo (2) and LVEF <28%. Levels of plasma NT-proBNP can detect low-functional class patients and patients who may be the candidates for heart transplantation with high sensitivity and specificity. At baseline and peak exercise, NT-proBNP demonstrates similar prognostic and predictive ability.

Topics: Adult; Aged; Biomarkers; Echocardiography; Exercise Test; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Peptide Fragments; Predictive Value of Tests; Prognosis; Rest; Stroke Volume; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) is a promising marker for heart failure diagnosis and prognosis. Although psychological factors also influence heart failure (HF) prognosis, this might be attributed to confounding by BNP. Our aim was to examine the association between multiple psychological markers using a prospective study design with repeated N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements.. The sample comprised 94 outpatients with systolic HF (80% men; mean age =62.2 ± 9.3). The psychological markers (i.e., anxiety, depression, and Type D personality), assessed with the Hospital Anxiety and Depression Scale (HADS), the Beck Depression Inventory (BDI), and the Type D Scale (DS14) were assessed only at baseline. Plasma NT-proBNP levels were measured at baseline and at 9 months.. The prevalence of anxiety, depression, and Type D personality at baseline was 23.4% (HADS-A), 17.0% (HADS-D), 46.6% (BDI), and 21.3% (DS14), respectively. At baseline, none of the psychological risk markers were associated with NT-proBNP levels (all p >.05). In the subset of patients with scores on psychological risk markers both at baseline and at 9 months, there were no association between anxiety (p =0.44), depression (HADS-D: p =0.90; BDI: p =0.85), and Type D (p =0.63) with NT-proBNP levels using ANOVA for repeated measures.. Our findings indicate that measures frequently used in HF to assess psychological risk markers are unconfounded by NT-proBNP. Futher studies are warranted to replicate these findings and examine whether psychological risk markers are independent predictors of prognosis in HF or an artifact that may be attributed to other biological or behavioral mechanisms.

Topics: Aged; Analysis of Variance; Anxiety; Biomarkers; Confounding Factors, Epidemiologic; Denmark; Depression; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Personality; Personality Assessment; Prevalence; Prospective Studies; Psychiatric Status Rating Scales

Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95% confidence interval 0.9 to 2.4, p = 0.16) for quartile 2, 1.7 (0.9 to 2.5, p = 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4 and 1.7 (1.2 to 2.5, p = 0.003) for abnormal versus normal level of hs-cTnT. In patients without CAD, quartile 4 of hs-cTnT was associated with an adjusted hazard ratio of 6.8. In conclusion, hs-cTnT is increased in most outpatients with chronic systolic HF and carries prognostic information beyond clinical parameters and amino-terminal pro-B-type natriuretic peptide. Increased hs-cTnT indicated a particularly deleterious prognosis in patients without CAD.

Topics: Aged; Aged, 80 and over; Chronic Disease; Cohort Studies; Coronary Artery Disease; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke Volume; Survival Rate; Troponin T; Ventricular Dysfunction, Left

We investigated the acute effects of implantable cardioverter-defibrillator shock on myocardium, cardiac function, and hemodynamics in relation to left ventricular systolic function.. We studied 50 patients who underwent implantable cardioverter-defibrillator implantation and defibrillation threshold (DFT) testing: 25 patients with left ventricular ejection fraction (LVEF) ≥ 45% and 25 patients with LVEF <45%. We measured cardiac biomarkers (creatine kinase, creatine kinase-MB, myoglobin, cardiac troponin T and I, and N-terminal probrain natriuretic peptide). Left ventricular relaxation was assessed by global longitudinal strain rate during the isovolumetric relaxation period using speckle-tracking echocardiography. Blood sampling and echocardiography were performed before, immediately after, and 5 minutes and 4 hours after DFT testing. Mean arterial pressure was measured directly during DFT testing. Cardiac biomarkers showed no significant changes in either group. LVEF was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in the group with reduced LVEF (P<0.001), whereas LVEF reduction was not observed in the group with preserved LVEF (P=0.637). Global isovolumetric relaxation period was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in both groups (preserved LVEF: 0.39 ± 0.14 versus 0.23 ± 0.13* versus 0.23 ± 0.13* versus 0.40 ± 0.13 s(-1), *P<0.001 versus baseline; reduced LVEF: 0.15 ± 0.05 versus 0.08 ± 0.04† versus 0.09 ± 0.04† versus 0.15 ± 0.05 s(-1), †P<0.001 versus baseline, repeated-measures ANOVA). Time to recovery of mean arterial pressure to the baseline was prolonged in the group with reduced LVEF (P<0.001).. Implantable cardioverter-defibrillator shock transiently impairs cardiac function and hemodynamics especially in patients with systolic dysfunction, although significant tissue injury is not observed.

Topics: Analysis of Variance; Biomarkers; Creatine Kinase; Creatine Kinase, MB Form; Defibrillators, Implantable; Echocardiography; Female; Heart Failure, Systolic; Hemodynamics; Humans; Male; Middle Aged; Myoglobin; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Troponin I; Troponin T; Ventricular Dysfunction, Left

Red blood cell distribution width (RDW), a measure of anisocytosis, is a prognostic biomarker for heart failure (HF). However it is still unclear how RDW is associated with heart function and established cardiac biomarkers.. In a prospective hospital cohort of 296 patients referred for echocardiography because of suspected HF, blood sampling and clinical examination were performed within 24h after echocardiography. The patients were divided into four HF groups, including one group where the HF diagnosis was uncertain (gray zone). In the patients the mean age was 70 ± 11 years, 44% with systolic HF (SHF), 18% with heart failure with normal ejection fraction (HFNEF), 17% with gray zone and 21% without HF (non-HF). RDW was higher among patients with SHF and HFNEF, compared with gray zone and non-HF patients. The distribution of different variables over the RDW quartiles showed an inverse correlation between RDW levels and LVEF and a positive correlation between RDW and NT-proBNP levels. Further analysis with stepwise multiple linear regression demonstrated that NT-proBNP levels, but not LVEF, were independently correlated with RDW.. In patients referred for echocardiography because of suspected HF, RDW levels were higher in patients with SHF and HFNEF. Moreover, NT-proBNP levels were independently linked with elevated RDW.

Topics: Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Echocardiography; Erythrocyte Indices; Female; Heart Failure; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Stroke Volume

Despite advances in medicine, chronic systolic heart failure (CHF) due to hypertension still constitutes a serious clinical challenge.. The aim of the study was to determine risk mortality factors in a 3-year follow-up of patients with CHF due to hypertension.. The study involved 140 consecutive stable inpatients with CHF (left ventricular end diastolic diameter >57 mm; left ventricular ejection fraction [LVEF] <40%), without epicardial artery stenosis (>30% vessel lumen), significant heart defect, diabetes, neoplastic, disease, or chronic kidney disease, with a minimum 5-year history of hypertension, and administration of angiotensin-converting enzyme inhibitors (or angiotensin II receptor antagonists), β-adrenolytics, spironolactone and furosemide for 3 or more months. The follow-up began on admission to the hospital after laboratory tests, resting electrocardiogram and echocardiogram, six-minute walk test, coronarography, and endomyocardial biopsy. Late follow-up data was obtained from the follow-up visits or by telephone.. The analysis involved 130 of 140 patients aged 47.8 ±7.9 years. The 3-year mortality rate was 18.5%. Independent risk factors for death were LVEF (hazard ratio [HR], 0.881; 95% confidence interval [CI], 0.797-0.975, P <0.05), serum glucose (HR, 1.266; 95% CI, 1.085-1.627; P <0.05), N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.369; 95% CI, 1.166-1.671; P <0.001), and bilirubin levels (HR, 1.057; 95% CI, 1.021-1.094; P <0.01).. Beside LVEF and serum NT-proBNP, other independent risk factors for death in patients with CHF due to hypertension are glucose and bilirubin levels.

Topics: Adult; Aged; Biomarkers; Causality; Chronic Disease; Comorbidity; Confidence Intervals; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Ventricles; Hospitalization; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prognosis; Severity of Illness Index; Survival Analysis; Troponin T

Ivabradin is indicated in patients with compensated chronic heart failure and sinus rhythm with resting heart rate 75 beats per minute despite maximal tolerated beta-blocker dose. Three case reports show favourable effect of ivabradin therapy on heart rate, reverse cardiac remodeling and B-type natriuretic peptide concentration in patients with systolic heart failure.

Topics: Adult; Aged; Benzazepines; Chronic Disease; Cyclic Nucleotide-Gated Cation Channels; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left; Ventricular Remodeling

Topics: Female; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain

Topics: Benzazepines; Cyclic Nucleotide-Gated Cation Channels; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left

Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and WRF.. A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT-pro-BNP with WRF was analysed during a follow up of 18 months.. Twenty-eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063-4765) had significantly higher baseline NT-pro-BNP values than patients without WRF (547 pg/mL, IQR 173-1454). The risk for WRF increased by 4.0 (95% CI 2.1-7.5) for each standard deviation of log NT-pro-BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT-pro-BNP and diabetes were independent predictors of WRF. At a cut-off level of 696 pg/mL, NT-pro-BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF.. NT-pro-BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno-protective strategies in patients with elevated NT-pro-BNP.

Topics: Aged; Biomarkers; Chronic Disease; Disease Progression; Female; Heart Failure, Systolic; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Protein Precursors

The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.

Topics: Amides; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Enalapril; Fumarates; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renin; Renin-Angiotensin System; Research Design; Stroke Volume; Ventricular Function, Left

The ratio of peak transmitral pulsed Doppler early velocity to early diastolic tissue Doppler velocity (TDI) of the lateral or septal mitral annulus (E/Ea) is considered a reliable estimation of LV filling pressure. We aim to examine the impact of left ventricular (LV) dimensions on the relationship between lateral and septal E/Ea in the determination of diastolic dysfunction patterns in the setting of chronic systolic heart failure (HF).. In 207 patients with chronic systolic HF (LV ejection fraction ≤40%, New York Heart Association Classes I-IV), comprehensive transthoracic echocardiography was performed and long-term outcomes followed up to a median of 40 months. The median lateral and septal Ea (interquartile range) were 7.0 (4.7 to 9.5) cm/s and 4.5 (3.5 to 5.6) cm/s, respectively. The median E/lateral Ea, E/septal Ea, and E/average Ea (interquartile range) were 10.8 (7.1 to 15.1), 16.1 (11.1 to 23.0), and 12.7 (8.8 to 17.7), respectively. In the first 2 tertiles of indexed left ventricular end-diastolic volume (LVEDVi) (<92 mL/m(2) and 92 to 130 mL/m(2)), all 3 E/Ea indices rise with increasing diastolic stage (all P < .001). However, in the highest tertile of indexed LVEDVi (≥130 mL/m(2)), E/average Ea and E/septal Ea (but not E/lateral Ea) increased with increasing diastolic stage, and only E/septal Ea correlated with natriuretic peptide levels (r = 0.38, P = .018) and adverse cardiac events (Hazard ratio 1.91, 95% confidence interval 1.25 to 2.96, P = .003).. In the setting of chronic systolic heart failure with extensive cardiac remodeling, septal TDI measurements may be more reliable and clinically relevant than lateral TDI measurements in the assessment of diastolic dysfunction.

Topics: Echocardiography; Female; Heart Failure, Systolic; Heart Septum; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Statistics, Nonparametric; Ultrasonography, Doppler; Ventricular Dysfunction, Left; Ventricular Remodeling

In order to study special characteristics of chronotropic reaction to physical exercise on veloergometer in the presence of obstructive sleep apnea (OSA) we examined 84 patients with manifestations of chronic systolic heart failure (HF). Chronotropic insufficiency was found in 88% of patients predominantly in combination with insufficient lowering of heart rate after exercise. At the same time it was more rarely registered in patients with OSA (56.4%). Insufficient lowering of heart rate by the end of first minute of rest was similarly associated with HF and OSA.. it is necessary to consider simultaneously chronotropic reserve and character of HR recovery after exercise.

Topics: Aged; Chronic Disease; Echocardiography; Exercise Test; Exercise Tolerance; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Physical Fitness; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive

Survival of patients with systolic heart failure (HF) may be influenced by the presence of chronic atrial fibrillation (AF) and circulating concentrations of B-type natriuretic peptides. In this study, we sought to assess the prognostic value of chronic AF in comparison to those of amino-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels and of echocardiographic parameters among HF patients of the entire study population and in those with AF.. Plasma NT-proBNP levels and echocardiography were prospectively assessed in 489 patients with chronic systolic HF (LV ejection fraction

Topics: Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Assessment; ROC Curve; Survival Analysis

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) levels showed frequent discrepancies in individual patients.. The aims were 1) to compare the abilities of BNP and NTproBNP for the detection of left ventricular systolic dysfunction (LVSD) or diastolic dysfunction (LVDD) in the symptomatic patients, and 2) to assess the direct correlation and its independent determinants between them.. 1032 patients with dyspnea underwent BNP and NTproBNP measurements simultaneously. 967/1032 (93.7%) patients underwent echocardiography. Using the receiver operation characteristic curve analyses for the detection of LVSD (EF<45%) or advanced LVDD, the area under the curves (AUC) of both biomarkers was compared according to age, gender, body mass index (BMI), hemoglobin (Hb), and glomerular filtration rate (eGFR). Using multiple regression analysis, the direct correlation and its independent determinants were identified between them.. In the entire population, the AUCs of BNP and NTproBNP had no significant differences (LVSD: 0.909 vs. 0.893, p=0.20; advanced LVDD: 0.897 vs. 0.879, p=0.13). In patients with BMI<25, the AUCs of BNP were significantly higher than those of NTproBNP (LVSD: 0.897 vs. 0.869, p=0.03; advanced LVDD: 0.916 vs. 0.885, p=0.02). They had strong correlation (r=0.895, p<0.001) and LVEF, eGFR<60 ml/min, Hb<12 g/dl and use of diuretics were the independent determinants between them.. BNP and NTproBNP displayed strong correlation and near-identical performances for the screening of cardiac dysfunction. However, LVEF, renal function, Hb and use of diuretics should be considered for clinical interpretation.

Topics: Aged; Biomarkers; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ventricular Dysfunction, Left

High adiponectin concentrations have emerged as an independent risk factor of outcome inpatients with CHF (chronic heart failure); however, modification of adiponectin in CHF patients has not been assessed to date. The aim of the present study was to investigate the effect of exercise training on adiponectin levels in CHF patients. A total of 80 patients with CHF due to systolic dysfunction were included. The effect of 4 months exercise training was studied in 46 patients,whereas the remaining 34 untrained CHF patients served as a sedentary control group. Circulating adiponectin concentrations, exercise capacity, anthropometric data and NT-proBNP (N-terminal pro-brain natriuretic peptide) levels were assessed. Adiponectin levels were significantly higher in CHF patients compared with healthy subjects [9.3 (7.1-16.1) and 4.9 (3.9-8.6) mg/l respectively;P=0.015]. Stratification of CHF patients according to tertiles of NT-proBNP revealed an increase in adiponectin with disease severity (P<0.0001). Exercise training reduced circulating adiponectin levels in CHF patients [10.7 (7.2-17.6) mg/l before training to 9.4 (5.9-14.8) mg/l after training;P=0.013], whereas no changes were observed in the sedentary CHF group [9.0 (7.0-13.5) mg/l before training and 10.1 (6.0-15.7) mg/l after a similar time interval]. A significant time x group interaction (P=0.008) was observed for the mean change in adiponectin between the trained and untrained CHF patients. Adiponectin concentrations were positively associated with NT-proBNP and HDL (high-density lipoprotein)-cholesterol and negatively correlated with BMI (body mass index), triacylglycerols and exercise capacity. In conclusion, circulating adiponectin concentrations are higher in CHF patients compared with healthy subjects and increase with disease severity.Exercise training for 4 months lowers circulating adiponectin levels.

Topics: Adiponectin; Case-Control Studies; Chronic Disease; Exercise; Exercise Tolerance; Female; Heart Failure, Systolic; Humans; Lipoproteins, HDL; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Regression Analysis

Metalloproteinases have been proposed as biochemical markers of left ventricular (LV) remodeling in systolic heart failure (HF). However, their role in the prognostic stratification of these patients remains controversial. In the present study, we aimed at investigating the value of plasma metalloproteinases-3 and -9 in comparison with N-terminal protype-B natriuretic peptide in patients with systolic HF. One hundred and 27 consecutive patients hospitalized for systolic HF (LV ejection fraction < 45%) were enrolled. Coronary artery disease (CAD) was the aetiology in 67% of the study patients. Plasma metalloproteinases-3 and -9 and N-terminal protype-B natriuretic peptide levels were assessed. A complete echocardiographic and Doppler examination was also performed. Follow-up period was 24-15 months. On univariate analysis, a number of measurements predicted cardiac events in the following order of power: NYHA class >2, LV ejection fraction < 25%, metalloproteinases-9 > 238 ng/ml, mitral E wave deceleration time < 150 ms, N-terminal protype-B natriuretic peptide > 1586 pg/ml and metalloproteinases-3 > 15 ng/ml. However, on multivariate analysis the only independent variables of cardiac events were NYHA class (OR=2.26, p=0.059) and plasma metalloproteinases-9 (OR=2.00, p=0.029). On Kaplan-Meier survival analysis, patients with elevated levels of metalloproteinases-9 exhibited a significantly worse event free-survival at 45 months than those without (21% vs. 54%, log-rank: 13.93, p=0.0002). A worse survival was also observed in patients with elevated N-terminal protype-B natriuretic peptide levels with respect to those without (18% vs. 46%, log-rank: 9.11, p=0.025). Our results demonstrated the value of plasma metalloproteinases-9 levels for prognostication of patients with systolic HF and a high prevalence of CAD.

Topics: Aged; Aged, 80 and over; Biomarkers; Coronary Artery Disease; Disease-Free Survival; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Male; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

This study was designed to ascertain whether the combination of Doppler assessment of the ratio of mitral blood flow to myocardial early diastolic velocities (E/E(m) ratio) and plasma N-terminal pro-type B natriuretic peptide (NT-proBNP) testing is useful to better stratify patients with stable systolic heart failure (HF).. A total of 362 outpatients with chronic systolic HF (left ventricular ejection fraction or=12), 77% in those with the E/E(m) ratio in the intermediate third, and 86% in those with the E/E(m) ratio in the lower third (

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Flow Velocity; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are useful biomarkers in patients with chronic heart failure (CHF). However, the clinical use has limitations due to the low sensitivity of a conventional commercial assay system. Recently, a high sensitive-cTnI (hs-cTnI) commercial assay has become available.. To compare the prognostic value of cTnT and hs-cTnI, we measured hemodynamic parameters and serum levels of cTnT, hs-cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP)in 258 consecutive CHF patients and then followed these patients for a mean period of 2.6 years. In both assays of cTnT and hs-cTnI, the lowest concentration at which the coeffi cient of variation was < or =10% were 0.03 ng/mL, respectively. Therefore, in the present study, an elevated cTnT or cTnI test was defined as a level of > or =0.03 ng/mL.. During long-term follow up, there were 20 cardiac deaths. In 258 CHF patients, serum cTnT were elevated (> or =0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI was elevated (> or =0.03 ng/mL) in 112 patients (43%). On stepwise multivariate analyses, high plasma NT-proBNP (> or =627 pg/mL, P = .0063) and hs-cTnI (> or =0.03 ng/mL) (P = .016) were independent significant prognostic predictors but cTnT (> or =0.03 ng/mL) was not. The hazard ratio for mortality of patients with high plasma NT-proBNP (> or =627 pg/mL) and hs-cTnI (> or =0.03 ng/mL) was 5.74 (95% CI, 2.33-14.28, P < .0001) compared to that of those with low NT-proBNP (<627 pg/mL) or hs-cTnI (<0.03 ng/mL).. These findings indicate that a high plasma concentration of hs-cTnI is an independent and useful prognostic predictor in patients with CHF.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Cohort Studies; Female; Heart Failure, Systolic; Heart Function Tests; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Stroke Volume; Survival Analysis; Troponin I

B-type natriuretic peptide (BNP) is produced as a biologically inactive prohormone (proBNP(1-108)), processed, and released as an inactive amino acid N-terminal fragment (proBNP(1-76)) and a biologically active carboxyl-terminal fragment (proBNP(77-108) or BNP32). We hypothesized that simultaneous assessment of proBNP(1-108) and active BNP32, as an index of natriuretic peptide processing efficiency, would improve risk stratification in patients with chronic systolic heart failure.. We quantified plasma proBNP(1-108) and BNP32 in 756 participants in the Penn Heart Failure Study, a prospective cohort of outpatients with predominantly systolic heart failure. Cox models were used to determine the association between biomarker level at the time of study entry and incident risk of adverse cardiovascular outcomes. A significant amount of unprocessed proBNP(1-108) circulates in patients with systolic heart failure (median, 271 pg/mL; interquartile range, 65 to 825). Higher levels of proBNP(1-108) were associated with an increased risk of all-cause death or cardiac transplantation (adjusted hazard ratio, 4.9; 95% CI, 2.5 to 9.7; P<0.001, comparing third versus first proBNP(1-108) tertile). ProBNP(1-108) provided additive information to BNP32 risk assessment, particularly in patients with BNP32 less than the median of 125 pg/mL (adjusted hazard ratio, 1.4; 95% CI, 1.2 to 1.8; P<0.001 per doubling of proBNP(1-108)).. Circulating proBNP(1-108) is independently associated with an increased risk of adverse cardiovascular outcomes in ambulatory patients with chronic systolic heart failure. The combined assessment of BNP32 and proBNP(1-108) provides additional information in determining risk of adverse clinical outcomes, particularly in patients with low BNP32 values that might otherwise be reassuring to the clinician.

Topics: Analysis of Variance; Biomarkers; Chi-Square Distribution; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Risk Assessment

Cheyne-Stokes breathing (CSB) has been associated with heart failure (HF) patients for many years; however, its true prevalence and its prognostic implications are still obscure.. The goal of this study was to investigate the prevalence and the possible prognostic implications of nocturnal CSB in advanced heart failure patients.. We performed single night full polysomonography ambulatory sleep studies in 71 HF patients. We analyzed the patients' sleep studies, clinical and laboratory data, and 6 month mortality.. A total of 71 chronic systolic HF patients were analyzed, 60 males, 11 females, age 65 +/- 13 years. Mean left ventricular ejection fraction was 27% +/- 11%. Short episodes of CSB (at least 3 min duration) were present in all patients, and mean CSB duration was 1 hour. CSB duration was associated significantly with both high serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) as well as with 6 month mortality. Log CSB time had a significant correlation with log NT-proBNP (r = 0.5, P<.0001). Based on median CSB duration, the Kaplan-Meier survival curve analysis showed significant association with 6 month mortality (P = .03).. CSB prevalence in advanced HF patients is higher than previously reported and is associated with increased serum levels of NT-proBNP and higher 6 month mortality.

Topics: Aged; Cheyne-Stokes Respiration; Disease Progression; Electrocardiography, Ambulatory; Female; Health Status Indicators; Heart Failure, Systolic; Humans; Israel; Kaplan-Meier Estimate; Male; Middle Aged; Monitoring, Ambulatory; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Prospective Studies; Risk Factors; Severity of Illness Index; Sleep Apnea Syndromes; Statistics as Topic; Stroke Volume; Ventricular Function, Left

To explore the negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity of natriuretic peptides, cut-off levels, and the impact of gender and age in elderly patients with systolic heart failure (HF).. Cross-sectional exploratory study.. One primary healthcare centre.. A total of 109 patients with symptoms of HF were referred for echocardiographic examination with a cardiovascular consultation. Systolic HF was diagnosed (ESC guidelines) in 48 patients (46% men, 54% women, mean age 79 years) while 61 patients (21% men, 79% women, mean age 76 years) had no HF.. NPV, PPV, sensitivity, specificity, and cut-off levels.. Including all 109 patients, NPV was 88% for NT-proBNP (200 ng/L) and 87% for BNP (20 pg/ml). PPV was 81% for NT-proBNP (500 ng/L) and 68% for BNP (50 pg/ml). Sensitivity was 96% for NT-proBNP (100 ng/L) and 96% for BNP (10-20 pg/ml). Specificity was 87% for NT-proBNP (500 ng/L) and 71% for BNP (50 pg/ml). Nt-proBNP (beta = 0.035; p < 0.001) and BNP (beta = 0.030; p < 0.001) were associated with age, but not with gender. In a multivariate analysis age (beta = 0.036; p < 0.001) and male gender (beta = 0.270; p = 0.014) were associated with NT-proBNP, but only age for BNP (beta = 0.030; p < 0.001).. Natriuretic peptides in an elderly population showed high NPVs, but not as high as in younger patients with HF in other studies. Age and male gender were associated with higher levels of NT-proBNP while only age was related to elevated BNP levels.

Topics: Age Factors; Aged; Biomarkers; Community Health Centers; Cross-Sectional Studies; Family Practice; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Sex Factors; Ultrasonography

To determine the relationship between galectin-3 concentrations and cardiac structure in patients with acute dyspnoea, and to evaluate the impact of galectin-3 independent of echocardiographic measurements on long-term mortality.. One hundred and fifteen patients presenting to the emergency department with acute dyspnoea who had galectin-3 levels and detailed echocardiographic studies on admission were studied. Galectin-3 levels were associated with older age (r = 0.26, P = 0.006), lower creatinine clearance (r = -0.42, P < 0.001), and higher levels of N-terminal-proBNP (r = 0.39, P < 0.001). Higher galectin-3 levels were associated with tissue Doppler E/E(a) ratio (r = 0.35, P = 0.01), a lower right ventricular (RV) fractional area change (r = -0.19, P = 0.05), higher RV systolic pressure (r = 0.37, P < 0.001), and more severe mitral (r = 0.30, P = 0.001) or tricuspid regurgitation (r = 0.26, P = 0.005). In patients diagnosed with heart failure (HF), the association between galectin-3 and valvular regurgitation and RV systolic pressure persisted. In a multivariate Cox regression model, galectin-3 remained a significant predictor of 4-year mortality independent of echocardiographic markers of risk. Dyspnoeic patients with HF and galectin-3 levels above the median value had a 63% mortality; patients less than the median value had a 37% mortality (P = 0.003).. Among dyspnoeic patients with and without ADHF, galectin-3 concentrations are associated with echocardiographic markers of ventricular function. In patients with ADHF, a single admission galectin-3 level predicts mortality to 4 years, independent of echocardiographic markers of disease severity.

Topics: Acute Disease; Age Factors; Aged; Biomarkers; Creatinine; Dyspnea; Echocardiography, Doppler; Female; Galectin 3; Heart Failure, Systolic; Heart Ventricles; Humans; Male; Mitral Valve Insufficiency; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Factors; Statistics, Nonparametric; Systole; Time Factors; United States

Diastolic dysfunction in patients with heart failure has prognostic relevance, possibly because of its relationship with worsening haemodynamic status. In the quest for simpler indexes of haemodynamic status in patients, brain natriuretic peptide (BNP) levels have been proposed as a surrogate of diastolic function. To date, the value of combining BNP levels with non-invasive haemodynamic monitoring by transthoracic electric bioimpedance (TEB) for the prediction of diastolic function has not been evaluated.. We compared left ventricular diastolic function measured by tissue Doppler imaging (TDI) with TEB results and BNP levels in 120 patients with chronic advanced systolic heart failure on optimal treatment (70 +/- 9 years, NYHA 2.4 +/- 0.8, ejection fraction 31 +/- 5%). Of the TEB variables measured, we only considered thoracic fluid content (TFC). To describe diastolic function, we used the TDI of the velocity of displacement of the mitral annulus (E') and the ratio E/E'. In all patients, E/E' was significantly related to TFC and to BNP levels (P < 0.001). Moreover, the combination of BNP > or = 350 pg/mL and TFC > or = 35/kOmega identified patients with diastolic dysfunction (defined as E/E' > or = 15) with high sensitivity and specificity (95 and 94%, respectively).. The combination of transthoracic bioimpedance monitoring and BNP measurement accurately indicated the presence of diastolic dysfunction in most patients. These user-friendly and operator-independent tools may be useful as a screening assessment for diastolic dysfunction, and consequently abnormal central haemodynamic status, either in ambulatory patients or when an adequate echocardiographic evaluation is not readily available.

Topics: Aged; Biomarkers; Cardiography, Impedance; Diastole; Disease Progression; Echocardiography, Doppler, Color; Electric Impedance; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Reproducibility of Results; Severity of Illness Index; Ventricular Dysfunction, Left

Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF.. In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 microg/L, or 100-300 microg/L with transferrin saturation <20%. The prevalence of ID was 37 +/- 4% [+/-95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P < 0.01).. In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.

Topics: Aged; C-Reactive Protein; Chronic Disease; Disease-Free Survival; Female; Ferritins; Heart Failure, Systolic; Humans; Iron Deficiencies; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Transferrin

In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status.. Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 +/- 6.0 and 40.2 +/- 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF.. Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.

Topics: Aged; Cardiac Output; Diuretics; Dose-Response Relationship, Drug; Echocardiography; Exercise Test; Follow-Up Studies; Furosemide; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Plasma Volume; Prognosis; Protein Precursors; Retrospective Studies; Sodium; Sodium Chloride, Dietary

Corin is a serine protease that cleaves pro-atrial and pro-B-type natriuretic peptides into biologically active hormones. The relationship between soluble plasma corin levels, plasma natriuretic peptide levels, myocardial structure and performance, and long-term clinical outcomes in the setting of chronic systolic heart failure has not been described.. In 126 patients with chronic systolic heart failure (left ventricular ejection fraction

Topics: Adult; Aged; Biomarkers; Cardiomegaly; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Prognosis; Prospective Studies; Serine Endopeptidases

Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha.. To test the hypothesis of the possible beneficial impact of IL-10 on mortality in systolic heart failure patients in relation to their circulating TNFalpha levels.. We measured circulating levels of IL-10 and TNFalpha in 67 ambulatory systolic heart failure patients (age 65 +/- 13 years).. Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFalpha (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR 3.67, 95% confidence interval 1.14-11.78).. Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFalpha had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.

Topics: Aged; Body Mass Index; C-Reactive Protein; Cause of Death; Cholesterol; Chronic Disease; Creatinine; Echocardiography; Electrocardiography; Exercise Test; Female; Follow-Up Studies; Heart Failure, Systolic; Hemoglobins; Humans; Interleukin-10; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume; Troponin T; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Autonomic dysfunction is an important marker of prognosis in congestive heart failure (CHF) and may determine the symptoms and progression of CHF. The aim of our study was to investigate whether preserved autonomic function assessed by heart rate variability (HRV) analyses is related to absence of CHF symptoms despite prominently reduced systolic function.. The study had a cross-sectional observational design. Fifty patients with left ventricular ejection fraction (EF) below 40% were enrolled. The patients were divided into two groups according to their CHF symptomatic status as Group 1 (NYHA functional class I, asymptomatic group) and Group 2 (NYHA functional class ≥ II, symptomatic group). Plasma C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) levels, echocardiographic parameters and HRV indices were measured while the patients were clinically stable in each group. Possible factors associated with the development of CHF symptoms were assessed by using multiple regression analysis.. Baseline clinical characteristics and left ventricular EF were similar in the two groups. Serum CRP (15 ± 21 vs 7 ± 18 mg/L, p=0.011) and NT-proBNP levels (1935 ± 1088 vs 1249 ± 1083 pg/mL, p=0.020) were significantly higher in symptomatic group. The HRV parameters (SDNN: 78 ± 57 vs 122 ± 42 ms, p=0.001; SDANN: 65 ± 55 vs 84 ± 38 ms, p=0.024; SDNNi: 36 ± 41 vs 70 ± 46 ms, p<0.001; triangular index [Ti]: 17 ± 12 vs 32 ± 14, p<0.001) were also significantly depressed in symptomatic group. When multiple regression analysis was performed, only HRV indices of autonomic function were significantly associated with the asymptomatic status (SDNN, OR: 1.016, 95%CI: 1.002-1.031, p=0.028; SDNNi, OR: 1.030, 95%CI: 1.008-1.052, p=0.006; TI, OR: 1.088, 95%CI: 1.019-1.161, p=0.011).. Preserved autonomic functions were shown to be associated with absence of CHF symptoms independently of angiotensin converting enzyme inhibitor/angiotensin receptor blocker's treatment and BNP levels and may be protective against the development of CHF symptoms despite advanced left ventricular systolic dysfunction.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Asymptomatic Diseases; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Disease Progression; Echocardiography; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Stroke Volume; Systole; Ventricular Dysfunction, Left

In systolic heart failure (HF), preventing the development of severe symptoms, before patients are in advanced NYHA functional classes, is a worthwhile target of therapy. Early recognition of left ventricular (LV) diastolic dysfunction and neuroendocrine activation may have an important impact on patient's outcome.. To investigate whether N-terminal proBNP (NT-proBNP) and mitral flow and tissue Doppler (TD) diastolic parameters are incremental for risk stratification of systolic HF patients in NYHA class I and II.. The study consisted of 232 consecutive outpatients with systolic HF (ejection fraction [EF] 544 pg/ml (hazards ratio [HR]: 2.66; p=0.012), EF <37% (HR: 2.45; p=0.006), E

Topics: Aged; Aged, 80 and over; Diastole; Early Diagnosis; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure, Systolic; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Systole

Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses.. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60).. We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Chronic Disease; Epinephrine; Female; Heart Failure, Systolic; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Prognosis; Survival Rate

Decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) during treatment of chronic heart failure (CHF) is associated with improved prognosis. However, there is lack of data from community-based HF programmes. We hypothesized that plasma levels of NT-proBNP, measured after optimization of pharmacotherapy in patients with CHF, may provide independent prognostic information when compared with baseline values and conventional prognostic markers.. N-terminal pro-B-type natriuretic peptide was measured in 354 patients with CHF and left ventricular ejection fraction <45%, who had recently been enrolled in a community-based HF programme. Patients underwent a 6 min walk test and clinical, echocardiographic and laboratory examinations. Pharmacotherapy was optimized; 318 patients survived until the second examination and measurement of NT-proBNP, which was performed between the 4th and 6th month of follow-up. During a median follow-up of 38.8 months, 125 patients died. Follow-up log NT-proBNP was a better predictor of death than either baseline log NT-proBNP or change in NT-proBNP (chi(2): 46.5 vs. 30.4 and 12.5, all P < 0.001). N-terminal pro-B-type natriuretic peptide was consistently the strongest independent prognostic marker at predicting death or unplanned cardiovascular hospitalizations after baseline or follow-up assessment.. The measurement of NT-proBNP after optimization of pharmacotherapy provides stronger prognostic information than either the baseline value, the change in NT-proBNP, or other conventional methods of assessment.

Topics: Aged; Aged, 80 and over; Echocardiography; Exercise Test; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; Stroke Volume; Survival Rate; Systole; Time Factors; United Kingdom; Ventricular Dysfunction, Left

Both low free triiodothyronine (fT3) and high brain natriuretic peptide (BNP) have been separately described as prognostic predictors for mortality in heart failure (HF). We investigated whether their prognostic value is independent.. From January of 2001 to December of 2006, we prospectively evaluated 442 consecutive patients with systolic HF and no thyroid disease or treatment with drugs affecting thyroid function (age 65+/-12 years, mean +/- standard deviation, 75% were male, left ventricular ejection fraction 33% +/- 10%, New York Heart Association (NYHA) class I and II: 63%, NYHA class III and IV: 37%). All patients underwent full clinical and echocardiographic evaluation and assessment of BNP and thyroid function. Both cardiac and all-cause mortality (cumulative) were considered as end points. During a median 36-month follow-up (range 1-86 months), 110 patients (24.8%) died, 64 (14.4%) of cardiac causes. Univariate Cox model predictors of all-cause mortality and cardiac death were age, body mass index, creatinine, hemoglobin, ejection fraction, NYHA class, BNP, fT3, and thyroxine level. Multivariate analysis selected age, NYHA class, hemoglobin, BNP, and fT3 as independent predictors for all-cause mortality and NYHA class, BNP, and fT3 as independent predictors for cardiac mortality. Patients with low fT3 and higher BNP showed the highest risk of all-cause and cardiac death (odds ratio 11.6, confidence interval, 5.8-22.9; odds ratio 13.8, confidence interval, 5.4-35.2, respectively, compared with patients with normal fT3 and low BNP).. fT3 and BNP hold an independent and additive prognostic value in HF.

Topics: Aged; Biomarkers; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Reference Values; Risk Assessment; ROC Curve; Stroke Volume; Survival Analysis; Thyroxine; Triiodothyronine; Ventricular Function, Left

Brain natriuretic peptide (BNP) and N-Terminal pro natriuretic peptide (NT-proBNP) are widely accepted to diagnose congestive heart failure (CHF) in the emergency room. The aim of this study was to evaluate the value of BNP and NT-proBNP to diagnose CHF in primary care.. Clinical and Doppler-echocardiographic assessment of patients referred by their general practitioner (GP) with the diagnosis of CHF. Receiver operating curves were used to evaluate the accuracy of BNP and NT-proBNP for echocardiographically confirmed systolic and/or diastolic heart failure.. Three hundred and eighty four patients (mean age of 65) were included. One hundred and ninety three (50%) patients had systolic heart failure and 31 (8%) had isolated diastolic heart failure. Using currently recommended cut-off values of BNP (less than 100 pg/ml) and NT-proBNP (less than 125 pg/ml) for exclusion of CHF, BNP was false negative in 25% and NT-proBNP in 10% of the patients. The area under the curve was better for NT-proBNP than for BNP (0.742 vs. 0.691).. In this population with a high prevalence of CHF, BNP and NT-proBNP failed to adequately rule out CHF. GP's should be cautious when using BNP and NT-proBNP in primary care. An echocardiography remains compulsory in unexplained dyspnea.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Dyspnea; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Prospective Studies; Referral and Consultation; ROC Curve; Switzerland; Treatment Outcome

Midregional pro-atrial natriuretic peptide (MR-proANP) was assessed for the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power compared with B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (HF).. MR-proANP is a biologically stable natriuretic peptide measured by a recently developed assay, with potential advantages over conventional natriuretic peptides such as BNP and NT-proBNP.. We measured MR-proANP, BNP, and NT-proBNP in 797 patients with chronic HF.. All 3 natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [95% confidence interval (CI): 0.753 to 0.844]), BNP (0.803 [95% CI: 0.757 to 0.849]), and NT-proBNP (0.730 [95% CI: 0.681 to 0.778]). During a median observation time of 68 months, 492 (62%) patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables. Proportion of explained variation showed that NT-proANP (4.36%) was a significantly stronger predictor of death than both NT-proBNP (2.47%, p < 0.0001) and BNP (2.42%, p < 0.0001).. Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.

Topics: Atrial Natriuretic Factor; Confidence Intervals; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Risk Factors; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

The aim of the present study was to investigate the prognostic significance of chemosensitivity to hypercapnia in chronic heart failure (HF).. Increased chemosensitivity to hypoxia and hypercapnia has been observed in HF. The potential value of enhanced chemosensitivity to hypercapnia to risk prediction in systolic HF has not been specifically evaluated.. One hundred ten consecutive systolic HF patients (age 62 +/- 15 years, left ventricular ejection fraction [LVEF] 31 +/- 7%) underwent assessment of chemosensitivity to hypoxia and hypercapnia (rebreathing technique) and were followed up for a median period of 29 months (range 1 to 54 months). The end point was a composite of cardiac death and aborted cardiac death (ventricular tachyarrhythmia treated by cardioverter-defibrillator).. At baseline, 31 patients (28%) had enhanced chemosensitivity to both hypoxia and hypercapnia. Although they had the same LVEF as the 43 patients (39%) with normal chemosensitivity, they were more symptomatic (New York Heart Association functional class), had higher plasma brain natriuretic peptide and norepinephrine, steeper regression slope relating minute ventilation to carbon dioxide output (V(E)/V(CO2) slope), more Cheyne-Stokes respiration, and more ventricular arrhythmias (all p < 0.05). Four-year survival was only 49%, in marked contrast to 100% for patients with normal chemosensitivity (p < 0.001). On multivariate analysis, combined elevation in chemosensitivity was the strongest independent prognostic marker, even when adjusted for univariate predictors (V(E)/V(CO2) slope, Cheyne-Stokes respiration, LVEF, and brain natriuretic peptide, p < 0.05).. Increased chemosensitivity to both hypoxia and hypercapnia, eliciting neurohormonal derangement, ventilation instability, and ventricular arrhythmias, is a very serious adverse prognostic marker in HF.

Topics: Chemoreceptor Cells; Exercise Test; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Hypercapnia; Hypoxia; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Prognosis; Prospective Studies; Stroke Volume; Time Factors

Although B-type natriuretic peptide (BNP) has been used for the diagnosis of congestive heart failure in many clinical settings, its diagnostic role in critically ill patients remains uncertain. The body of literature suggests that BNP and N-terminal pro-BNP levels are not useful for the diagnosis of systolic or diastolic heart failure in the critically ill, including in patients with brain hemorrhage, due to poor specificity. However, these cardiac peptides may have a more promising prognostic role in this patient population.

Topics: Critical Illness; Diagnostic Errors; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results

To assess the concentration of B-type natriuretic peptide (BNP) as a predictor of heart failure in patients with acute ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) with successful and complete revascularization.. Out of a total of 220 patients with acute STEMI admitted to the Sisters of Mercy University Hospital in the period January 1 to December 31, 2007, only patients with acute STEMI undergoing primary PCI who had single vessel disease and were successfully revascularized were included in the study. Selected patients had no history of myocardial infarction or heart failure and a normal or near-normal left ventricular ejection fraction (> or =50%) assessed by left ventriculography at admission. Only 58 patients met the inclusion criteria for the study. Out of those, 6 patients refused to participate in the study, and another 5 could not be followed up, so a total of 47 patients were evaluated. Blood samples were taken for measurement of BNP levels at admission, 24 hours later, and 7 days later. Patients were followed up for 1 year. The primary outcome was reduction in left ventricular ejection fraction (LVEF) to <50% after 1 year.. Patients who developed echocardiographic signs of reduced systolic function defined as LVEF<50% had significantly higher values of BNP (> or =80 pg/mL) at 24 hours (P=0.001) and 7 days (P=0.020) after STEMI and successful reperfusion. Patients who had BNP levels > or =80 pg/mL after 7 days were 21 times more likely to develop LVEF<50 (odds ratio, 20.8; 95% confidence interval, 2.2-195.2; P=0.008).. BNP can be used as a predictor of reduced systolic function in patients with STEMI who underwent successful reperfusion and had normal ejection fraction at admission.

Topics: Angioplasty, Balloon, Coronary; Biomarkers; Croatia; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; ROC Curve; Ventricular Dysfunction, Left

Tumour necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a multifunctional cytokine that has recently been implicated in cardiovascular disease. The aim of this study was to define the plasma levels of sTWEAK in patients with stable chronic heart failure and evaluate the possibility of a prognostic impact of sTWEAK.. sTWEAK levels in plasma samples from 364 patients with systolic heart failure were compared with 36 control patients. The median levels of sTWEAK in heart failure patients were significantly lower than those of the control group (217 pg/mL, interquartile range 136-311 vs. 325 pg/mL, interquartile range 250-394 pg/mL). Moreover, sTWEAK levels were lower in patients with ischaemic cardiomyopathy vs. dilated cardiomyopathy and correlated significantly with functional NYHA class. Patients with plasma levels below a ROC-derived cut-off value of 227 pg/mL had a significantly higher mortality rate after 4 years. Upon univariate and multivariate analyses, sTWEAK levels below 227 pg/mL emerged as an independent predictor of subsequent death.. In contrast to other cytokines shown to be increased in heart failure patients, plasma levels of sTWEAK are significantly reduced in chronic stable heart failure. In addition, lower plasma levels of sTWEAK predict an adverse prognosis independent of established risk markers such as NT-proBNP.

Topics: Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Chronic Disease; Cytokine TWEAK; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Tumor Necrosis Factors

Corin, a transmembrane serine protease expressed in cardiomyocytes, cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide (BNP) into biologically active peptide hormones. The minor corin I555(P568) allele, defined by the T555I and Q568P mutations, is common in persons of African ancestry and associated with increased risk for hypertension and cardiac concentric hypertrophy. The corin gene product containing the T555I and Q568P mutations has significantly reduced natriuretic peptide processing capacity. We hypothesized that the corin I555(P568) allele would be associated with adverse outcomes and impaired BNP processing in blacks with systolic heart failure.. This is a retrospective study of 354 subjects in the African American Heart Failure Trial Genetic Risk Assessment in Heart Failure substudy. In the corin variant group (n=50) compared with corin nonvariant group (n=300), BNP-32 (amino acids 77 to 108) was lower (190 pg/mL versus 340 pg/mL, P=0.007), but the ratio of unprocessed BNP(1 to 108)/processed BNP-32 was significantly higher (P=0.05). Stratified analyses were conducted because of evidence of significant interaction between the corin I555(P568) allele and treatment assignment. In the placebo arm, multivariable analysis demonstrated that the corin I555(P568) allele was associated with increased risk for death or heart failure hospitalization (relative risk 3.49; 95% CI, 1.45 to 8.39; P=0.005); however, in the treatment arm (fixed-dose combination isosorbide-dinitrate/hydralazine), the corin I555(P568) allele was not associated with adverse outcomes.. We have identified a pharmacogenomic interaction in blacks with systolic heart failure. The corin I555(P568) allele is associated with an increased risk for death or heart failure hospitalization in patients receiving standard neurohormonal blockade, but the addition of fixed-dose combination isosorbide-dinitrate/hydralazine ameliorates this risk. A plausible mechanism for this pharmacogenomic interaction is the impaired processing of BNP in carriers of the corin I555(P568) allele as compared with noncarriers.

Topics: Black or African American; Cardiovascular Agents; Double-Blind Method; Drug Combinations; Female; Gene Frequency; Genetic Predisposition to Disease; Heart Failure, Systolic; Hospitalization; Humans; Hydralazine; Immunoassay; Isosorbide Dinitrate; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Mutation; Natriuretic Peptide, Brain; Phenotype; Proportional Hazards Models; Protein Processing, Post-Translational; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Serine Endopeptidases; Treatment Outcome; United States

Healthcare providers should be concerned with improving the quality of life (QOL) of patients with heart failure (HF) because disease-specific QOL is linked to disease progression. The present study investigated the significance of elevated b-type natriuretic peptide (BNP), NYHA classification and depression to HF-related QOL to develop better management strategies. Outpatient subjects with left ventricular systolic dysfunction (n=108; mean age=64.9+/-12) completed the self-administered Minnesota Living with Heart Failure questionnaire and the Center for Epidemiologic Studies Depression Scale. Functional status was measured using the New York Heart Association Classification (NYHA) and BNP concentrations were measured in plasma samples. Multiregression analysis determined that plasma BNP levels did not contribute significantly to the total QOL score while depression (r=0.63, t ratio=7.43, P<.0001) and NHYA class (r=0.47, t ratio=3.31, P<.001) were significant contributors. NYHA III subjects exhibited worse depression scores (II 15+/-7 and III: 22+/-10, P<.001) and elevated plasma BNP (II: 2.0+/-0.5 and III: 2.4+/-0.6, P<.001). Low-cost psychological assessments are recommended to evaluate depression and suggest that those HF patients with NYHA III be closely monitored for depression and reduced QOL.

Topics: Adaptation, Psychological; Adult; Aged; Aged, 80 and over; Depression; Disease Progression; Female; Health Status Indicators; Heart Failure, Systolic; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Psychometrics; Quality of Life; Regression Analysis; Stroke Volume; Surveys and Questionnaires; Ventricular Function, Left

Thoracic fluid content (TFC) is one of the basic parameters measured by impedance cardiography (ICG). The B-type natriuretic peptide (BNP) is a neuroendocrine mediator produced in the ventricular myocardium and released in response to the increase of wall tension.. To determine the relationship between TFC measured by ICG and BNP serum level in patients with systolic heart failure (HF).. The study population included 50 patients: a group of 30 patients with systolic HF in functional NYHA class II and III [27 males and 3 females, aged 53 +/- 6 years, with mean left ventricular ejection fraction (LVEF) 23 +/- 6%], and 20 controls without HF symptoms and preserved LVEF. The TFC and BNP serum level were measured on the same day.. Mean BNP serum concentration was 521 +/- 882 pg/ml in HF patients and 44 +/- 36 pg/ml in healthy controls (p = 0.02). The TFC values did not differ significantly between the two groups (27.3 +/- 4.5 1/kW in the study group versus 26.3 +/- 2.8 1/kW in control subjects, NS). A significant correlation between TFC and BNP was found in patients with overt HF (r = 0.57, p = 0.001); however, after excluding one patient with exacerbation of HF symptoms, the correlation was non-significant (r = 0.24, p = 0.22). No correlation between these parameters was observed in healthy controls (r = 0.17, p = 0.51).. There was no significant correlation between TFC measured by ICG and BNP serum level in haemodynamically stable patients with HF symptoms. The usefulness of ICG measurements in patients with exacerbated chronic HF needs further investigations.

Topics: Biomarkers; Body Fluids; Cardiography, Impedance; Chronic Disease; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Stroke Volume; Thoracic Cavity

The purpose of the present study was to determine whether change in plasma brain natriuretic peptide (BNP) level at an early phase of carvedilol therapy is a predictor of improvement in cardiac function and long-term prognosis in patients with systolic chronic heart failure (CHF).. Neurohumoral factors and haemodynamics were examined in 64 patients with systolic CHF (left ventricular ejection fraction (LVEF) below 45%) before and one month (early phase) and 3 to 6 months (late phase) after the start of carvedilol therapy. These patients were followed up for a mean period of 57 months. Plasma BNP levels were already decreased in the early phase before improvement of LVEF in response to carvedilol therapy. Univariate and multivariate linear regression analyses showed that Delta log brain natriuretic peptide (BNP)E (= log BNP at baseline--log BNP at early phase) (P < 0.0001) was a significant independent predictor of improvement in LVEF in the late phase. Cardiac events occurred in I I patients during the follow-up period. In addition, multivariate Cox proportional hazards regression analysis showed that Delta log BNPE (P = 0.0045) and systolic blood pressure at baseline (P = -0.048) were significant independent predictors of the development of cardiac events.. Decrease in plasma BNP level in the early phase of carvedilol therapy is a novel predictor of not only improvement of LVEF in the late phase but also prognosis in patients with systolic CHF.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Carvedilol; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Immunoradiometric Assay; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Retrospective Studies; Stroke Volume; Survival Rate; Time Factors; Treatment Outcome

Matrix metalloproteinase 9 (MMP-9) may serve as a biomarker of ventricular remodeling in selected populations, but few studies have assessed its performance in clinical practice. We tested MMP-9 as a biomarker of remodeling and predictor of outcomes in a systolic heart failure cohort derived from clinical practice and compared its performance to brain natriuretic peptide (BNP).. Plasma MMP-9 and BNP levels were measured in 395 outpatients with systolic heart failure who participated in the Penn Heart Failure Study. We tested for (1) cross-sectional associations between biomarker levels, left ventricular end-diastolic dimension index (LVEDDI), and ejection fraction (EF), and (2) associations between baseline biomarker levels and risk of subsequent cardiac hospitalization or death over 3 years of follow-up.. Matrix metalloproteinase 9 had no significant correlation with LVEDDI (rho = 0.04, P = not significant) or EF (rho = -0.06, P = not significant), whereas BNP showed highly significant correlations (LVEDDI: rho = -0.27, P < .0001; EF: rho = -0.35, P < .0001). In multivariate linear regression models, MMP-9 again showed no significant associations with LVEDDI (P = .6) or EF (P = .14), whereas BNP showed strong independent associations (LVEDDI: P < .001; EF: P = .002). Kaplan-Meier analyses showed no difference in hospital-free survival by baseline MMP-9 tertile (P = .7), whereas higher BNP tertile predicted worse survival (P < .0001). In multivariate Cox models, baseline MMP-9 level did not predict risk of adverse outcome (hazard ratio for log increase 0.98, P = .9), whereas BNP was a significant independent predictor (hazard ratio for log increase 1.15, P = .02).. Compared to BNP, MMP-9 is a poor clinical biomarker of remodeling and outcome in patients with systolic heart failure derived from clinical practice.

Topics: Adult; Aged; Biomarkers; Cross-Sectional Studies; Echocardiography; Female; Heart Failure, Systolic; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Ventricular Remodeling

Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) <40%, we assessed the impact of BNP assay, Doppler echocardiography and CPx on survival. Median BNP plasma levels were 207 [90-520] pg/mL. Mean LVEF was 33 +/- 7%. Left bundle branch block (LBBB) was present in 52 patients (33%) and a restrictive filling pattern in 35 (22%). The slope of the relation between minute ventilation and carbon dioxide production (VE/VCO(2) slope) averaged 35 +/- 8; an enhanced ventilatory response (EVR) to exercise (VE/VCO(2) slope >35) was found in 67 patients (43%). During 759 +/- 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO(2) slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.

Topics: Aged; Bundle-Branch Block; Exercise; Exercise Test; Female; Heart Failure, Systolic; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Pulmonary Ventilation; Risk Assessment; Stroke Volume; Ultrasonography

To analyze differences in brain natriuretic peptide (BNP) levels depending on mitral flow pattern (MFP) and to assess the effects of carvedilol on changes in MFP, left ventricular function and exercise capacity.. The study population consisted of 73 patients with symptomatic heart failure in NYHA classes II and III and LVEF < 40% without prior beta-blockade. In all patients at baseline, before carvedilol, and then at 3 and 12 months after initiation of treatment, the following parameters were assessed: HR(s), serum BNP, echocardiographic parameters, and exercise capacity with gas monitoring during cardiopulmonary stress test. Before carvedilol there was a positive correlation between BNP and E/A (r = 0.17; p = 0.05). BNP was significantly higher in patients with restrictive MFP (rMFP) as compared with nonrestrictive MFP (nrMFP) (541.5 +/- 206.7 vs. 412.6 +/- 207.2; p = 0.009), and lower VO(2peak) in rMFP as compared with nrMFP (12.5 +/- 3.7 vs. 16.5 +/- 4.7; p = 0.001). After initiation of carvedilol, the patients with rMFP had reduced E/A (2.9 vs. 1.4; p = 0.003), and rMFP was changed to nrMFP in 60.8% of patients. Respective BNP concentrations were 342.16 +/- 284.31 vs. 326.40 +/- 264.6; NS. In patients with rMFP VO(2peak) , %N increased significantly from 42.4 +/- 10.2 to 52.4 +/- 14.4; p = 0.012.. In patients with systolic congestive heart failure, the presence of rMFP is related to higher BNP levels and reduced VO(2peak). Chronic treatment with carvedilol replaces rMFP with nrMFP and improves exercise capacity in some patients.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analysis of Variance; Blood Flow Velocity; Carbazoles; Carvedilol; Case-Control Studies; Echocardiography, Doppler; Exercise Tolerance; Female; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Probability; Propanolamines; Reference Values; Risk Assessment; Severity of Illness Index; Stroke Volume; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left

The aim of this prospective study was to assess the diagnostic value of NT-proBNP and the concordance with Tissue Doppler Echocardiography (including strain and longitudinal displacement) in diastolic and systolic heart failure.. 137 consecutive clinically stable patients were included (42 healthy controls, 43 with diastolic heart failure, 52 with systolic heart failure). In diastolic heart failure, basal septal strain was reduced (-24.8 +/- 8.1% vs. controls. -18.5 +/- 5.3%, p < 0.0001). In all patients with preserved systolic function, septal basal longitudinal displacement was impaired in patients with increased left-ventricular filling pressures (E/E' < 8: 13.5 mm +/- 3.3 mm vs. E/E' > 15: 8.5 mm +/- 2.3 mm, p = 0.001) parallel to NT-proBNP elevation (E/E' < 8: 45.8 pg/ml, IQR: 172.5 pg/ml vs. E/E' > 15: 402.0 pg/ml, IQR: 1337.2 pg/ml; p = 0.0007). In ROC analysis, NT-proBNP could detect patients with reduced left ventricular systolic function (LVEF >or= 55%) with a good diagnostic accuracy. However, the diagnostic accuracy of NT-proBNP to detect diastolic dysfunction was lower.. Subtle changes of longitudinal myocardial function begin in diastolic heart failure and are further increased in systolic heart failure. In patients with preserved LV function, a complex approach with the integration of multiple parameters including Tissue Doppler echocardiography and NT-proBNP is necessary to classify patients.

Topics: Adult; Aged; Diagnosis, Differential; Echocardiography, Doppler; Female; Heart; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; ROC Curve; Severity of Illness Index; Young Adult

Based on the importance of left ventricular (LV) diastolic function in stratification of the cardiac prognosis in patients with systolic heart failure (SHF), we attempted to identify the prognostic impact of Doppler echocardiographic examinations and plasma B-type natriuretic peptide (BNP) concentration.. Of 73 patients admitted with decompensated SHF (ejection fraction <45%), 58 were included. Among these, 21 patients had ischemic heart disease and 27 non-ischemic dilated cardiomyopathy. In all patients, Doppler echocardiographic examinations and measurements of the plasma B-type natriuretic peptide concentration were simultaneously performed before discharge. Patients were followed up for 36 months after discharge. Primary end point for the follow-up was readmission for acute decompensated heart failure or cardiac death.. During the mean follow-up period of 28±12 months, 16 patients (27.6%) were readmitted with decompensated heart failure. Based on the stepwise multivariate Cox regression analysis, mitral E/A ratio (chi-square=6.5, relative risk=1.7, p=0.01) and BNP (chi-square=3.9, relative risk=1.7, p=0.04) were identified as independent predictors of primary endpoints. Based on ROC analysis, the optimal cutoff point of E/A was 1.05 (AUC=0.836, p=0.002) and that of plasma BNP concentration was ≥254.5 pg/ml (AUC=0.768, p=0.002). In high-risk patients with E/A ≥1, event-free survival rates were significantly lower in patients with BNP <254.5 pg/ml (p<0.001).. The complementary assessment of Doppler transmitral flow and plasma BNP concentration may be reliable in identifying the prognosis of patients with SHF.

Topics: Disease-Free Survival; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis

Despite the fact that B-type natriuretic peptide (BNP) is a useful diagnostic complement to clinical and radiographic data in the emergency diagnosis of acute congestive heart failure, levels of BNP in the mid-range (100-500 pg/ml) are acknowledged to be inconclusive for the diagnosis. We assessed the diagnostic value of the pulsed Doppler-derived isovolumic relaxation time (IVRT) by bedside Doppler echocardiography in the emergency diagnosis of new-onset congestive heart failure with preserved systolic function in 43 patients presenting with acute severe dyspnea and inconclusive BNP levels. A short IVRT <50 ms was a good predictor of acute congestive heart failure in this clinical setting, with a positive predictive value of 94%.

Topics: Echocardiography, Doppler; Heart Failure, Systolic; Humans; Myocardial Contraction; Natriuretic Peptide, Brain; Prognosis; Severity of Illness Index; Stroke Volume; Systole; Ventricular Function, Left

C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF.. HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population (n=7701) and associated with the HF admissions and mortality of the patients.. Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters (p<0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) (r=0.31 p=0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF (p=0.047).. HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated.

Topics: Aged; C-Reactive Protein; Case-Control Studies; Cohort Studies; Creatinine; Diabetes Mellitus; Female; Follow-Up Studies; Heart Failure, Diastolic; Heart Failure, Systolic; Hospitalization; Humans; Israel; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index

Epidemiological studies suggest that "diastolic heart failure" (DHF) is common and has a prognosis similar to that of systolic heart failure (SHF). We wanted to assess whether patients with breathlessness who were being treated for DHF had objective evidence of cardiac impairment and exercise limitation.. Consecutive patients with a clinical diagnosis of chronic heart failure completed a standardised 6-minute walk test (6-MWT) and underwent an echocardiographic examination to determine the presence of major structural heart disease (MSHD). N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured to determine degree of cardiac pathology.. 568 patients were identified with SHF (75.7% males) and 104 with DHF (54.7% males). They were compared with 400 healthy controls (matched with DHF group for age, sex and body mass index (BMI)). Controls (median (interquartile range); 43 (20-62) pmol/l)) and DHF patients (27 (13-67) pmol/l) had significantly lower NT-proBNP levels compared to SHF patients (178 (82-422) pmol/l). There was no difference in NT-proBNP levels between controls and DHF patients (p = 0.348). There was no correlation between BMI and NT-proBNP in either DHF (r(2) = 0.03; p = 0.287) or SHF (r(2) = 0.02; p = 0.346) patients. Both SHF and DHF patients reported similar degrees of breathlessness. 6-MWT distance (p = 0.973) was similar between SHF and DHF patients. DHF patients had a higher BMI (p<0.0001).. Patients being treated for a clinical diagnosis of DHF have the same self-reported symptoms and 6-MWT performance as patients with SHF, yet have normal NT-proBNP levels. Their perception of their symptoms is out of proportion to their evidence of cardiac pathology.

Topics: Aged; Aged, 80 and over; Attitude to Health; Biomarkers; Body Mass Index; Dyspnea; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Perception; Ultrasonography; Ventricular Dysfunction, Left

Half of the patients presenting to primary-care with signs and symptoms of heart failure (HF) are found not to have serious heart disease after echocardiographic assessment. This places an unnecessary burden on hospital services. We sought to assess the cost-benefit of screening for left ventricular systolic dysfunction (LVSD) and major structural heart disease (SHD) using N-terminal pro-B-type natriuretic peptide (NT-proBNP) and QRS-width from an electrocardiogram in patients presenting with suspected HF to primary-care physicians (PCP).. Patients were recruited from a community-based service pilot. Blood samples for NT-proBNP measurement were obtained in primary-care. All patients were referred irrespective of the NT-proBNP result, with echocardiograms reviewed by a cardiologist blinded to the NT-proBNP result.. NT-proBNP<180 pg/ml (21 pmol/l) 'ruled-out' major-LVSD avoiding 38% of echoes and 23% of cost compared with direct referral for echocardiography. NT-proBNP<93 pg/ml (11 pmol/l) 'ruled-out' major-SHD, avoiding 20% of echoes and 8% of cost. A QRS<84 ms 'ruled-out' major-LVSD, avoiding 28% of echoes and 17% of cost. A QRS<82 ms 'ruled-out' major-SHD avoiding 20% of echoes and 9% of cost. Intermediate values of NT-proBNP were often associated with equivocal echocardiography and in some scenarios NT-proBNP testing might avoid 61% of echocardiograms and 46% of cost.. Use of NT-proBNP by PCPs to detect major-LVSD and major-SHD in patients with suspected HF could reduce referrals for specialist HF-assessment, provide cost-avoidance compared to direct referral and improve the efficiency of care. QRS-width is less effective as a diagnostic test and adds little cost-benefit when combined with NT-proBNP.

Topics: Aged; Aged, 80 and over; Biomarkers; Cost-Benefit Analysis; Electrocardiography; Female; Health Care Costs; Heart Failure, Systolic; Humans; Male; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Primary Health Care; Referral and Consultation; ROC Curve; Ventricular Dysfunction, Left

Plasma B-type natriuretic peptide (BNP) is an emerging biomarker in heart failure. In this setting, the extent of left ventricular (LV) dyssynchrony contributes to exercise symptoms. Whether exercise-induced changes in LV dyssynchrony might be a trigger of BNP release has never been investigated.. Fifty-seven patients with systolic LV dysfunction underwent quantitative analysis of BNP, mitral regurgitation (MR), and dyssynchrony at rest and during exercise. None had inducible ischaemia on perfusion imaging. By multiple regression analysis, end-systolic volume index (P < 0.0001), effective regurgitant orifice (ERO) (P < 0.001), and E/Ea (P = 0.002) emerged as independent determinants of BNP at baseline (R(2) = 0.67). Exercise induced a significant rise in BNP levels (P < 0.0001). In multivariate analysis, a smaller change in systolic blood pressure (P = 0.04), a larger increase in ERO (P = 0.017), and in systolic dyssynchrony index (P = 0.006) during exercise emerged as independent determinants of exercise-induced increases in BNP (R(2) = 0.45).. MR severity, volume overload, and LV filling pressure are surrogates of BNP at rest. During exercise, changes in BNP reflect the presence of dynamic changes in both LV dyssynchrony and MR severity in the absence of inducible ischaemia.

Topics: Aged; Aged, 80 and over; Biomarkers; Electrocardiography; Exercise; Exercise Tolerance; Heart Failure, Systolic; Humans; Middle Aged; Mitral Valve Insufficiency; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Regression Analysis; Rest; Severity of Illness Index; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Drug Therapy, Combination; Enalapril; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Risk Assessment; Time Factors; Treatment Outcome

Invasive hemodynamic monitoring with Swan-Ganz catheterization to guide treatment decisions in heart failure may be hazardous and may lack prognostic value. We assessed the clinical utility of B-type natriuretic peptide (BNP) in estimating left ventricular filling pressures in patients with inconclusive tissue Doppler indexes. In this study, 50 patients with systolic heart failure and an early transmitral velocity to early diastolic mitral annular velocity ratio (E/Ea) between 8 and 15 were studied. Among them, 25 had been admitted for acutely decompensated heart failure (group A) and the remainder were clinically stable outpatients (group B). All patients underwent simultaneous invasive pulmonary capillary wedge pressure (PCWP) determination, BNP measurement, and echocardiography. In group A, BNP correlated with PCWP (r = 0.803, P < 0.001), deceleration time (DT, r = -0.602, p = 0.001), and end-systolic wall stress (SWS, r = 0.565, P = 0.003). In multivariate analysis, BNP was the only parameter independently associated with PCWP (P = 0.023). In group B, no correlation was found between BNP and PCWP or SWS, while DT correlated significantly with both PCWP (r = -0.817, P < 0.001) and BNP (r = -0.8, P < 0.001). We conclude that BNP may be a useful noninvasive tool for the assessment of left ventricular filling pressures in patients with acutely decompensated heart failure and inconclusive tissue Doppler indexes.

Topics: Aged; Biomarkers; Echocardiography, Doppler; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Wedge Pressure; Ventricular Function, Left; Ventricular Pressure

We have combined the measurement of N-terminal pro-B type natriuretic peptide (NTproBNP) with plasma peptide profiling to evaluate the effect on sensitivity and specificity of systolic heart failure (SHF) diagnosis. Plasma NTproBNP levels were measured from 100 SHF patients and 100 age/gender matched controls and plasma protein profiles obtained using MALDI-MS. Sixty-seven m/z peaks were significantly different between SHF and normals, and following logistic regression analysis with NTproBNP values, 6 peaks retained independent predictive value. Receiver operating characteristic (ROC) curves for SHF diagnosis had areas of 0.91 for NTproBNP, improving to 0.99 with the model. In a separate validation test set (32 SHF, 20 normals), the model remained highly accurate (ROC area 0.995). An artificial neural network with these 6 peak intensities and NTproBNP produced ROC areas of 0.99 in both training and test sets. The sensitivity and specificity of SHF diagnosis using NTproBNP in training (85, 85%) and test (93, 75%) sets was improved in the model for both training (96, 96%) and test (100, 95%) sets. The accuracy of SHF diagnosis using NTproBNP is improved by the use of a plasma profile of 6 peptide peaks, reducing the uncertainty in the diagnostic gray zone of using NTproBNP alone.

Topics: Aged; Biomarkers; Blood Proteins; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; ROC Curve; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels.. In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 +/-0.4 vs 1.8+/-0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01).. A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Flow Velocity; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Mitral Valve; Natriuretic Peptide, Brain; Ventricular Function, Left

N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis that anemia (World Health Organization criteria, hemoglobin levels <7.5 mmol/L for women and <8.0 mmol/L for men) and NT-pro-BNP are associated and evaluated how a possible association affects the prognostic value of each risk marker. Clinical data from 345 patients with systolic heart failure were obtained prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction <0.45, no exclusion criteria). Follow-up was 30 months (median), and 70 events (mortality) occurred. Prevalence of anemia was 27%. In a multivariate logistic regression model, anemia (p = 0.041) was closely associated with NT-pro-BNP levels above the median (1,381 pg/ml) after adjustment for traditional confounders (left ventricular ejection fraction, age, body mass index, atrial fibrillation, chronic kidney disease). In an adjusted Cox proportional hazard model, the 2 parameters were associated with mortality after adjustment for traditional confounders (hazard ratio for anemia 1.73, 95% confidence interval 1.06 to 2.83, p = 0.029; hazard ratio for NT-pro-BNP >1,381 pg/ml 2.68, 95% confidence interval 1.58 to 4.66, p <0.001). Patients with anemia and high NT-pro-BNP levels had a fivefold increased risk for mortality (hazard ratio 4.77, 95% confidence interval 2.47 to 9.18, p <0.001). In conclusion, anemia is closely associated with NT-pro-BNP in patients with systolic heart failure, and anemia and NT-pro-BNP carry independent prognostic information. Patients with anemia and high levels of NT-pro-BNP have a markedly increased mortality risk.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Outpatient Clinics, Hospital; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies

Based on the fact that NYHA class, plasma BNP level, and echocardiographic indices of left ventricular filling pressures are prognostic factors in chronic systolic heart failure, we evaluated their predictive value for acute decompensation following initiation and titration of bisoprolol in this illness.. Bisoprolol was initiated and/or increased according to the ESC/ACC/AHA recommendations in 50 patients with stable chronic systolic heart failure (age: 60+/-2 years, males: 88%) in NYHA class? 2 with a left ventricular ejection fraction (LVEF)<40% and a plasma creatinine<250 micromol/l. The clinical parameters, plasma BNP levels and echocardiographic indices were measured blind on the same day, on admission and then once a week for three weeks. On admission, the NYHA was 2.9+/-0.1, mean plasma creatinine 99+/-3 micromol/l, plasma BNP 503+/-57 pg/ml, LVEF 29+/-1%, E/A ratio 1.9+/-0.2, E/Ea ratio 8.8+/-0.3, E wave deceleration time 155+/-9 ms, systolic pulmonary artery pressure 40+/-2 mmHg and the diameter of the inferior vena cava was 16+/-1 mm. Over the course of follow up, an episode of acute decompensation occurred in 16% of the patients (8/50). Using univariate analysis, age and initial (admission) values for NYHA class, blood pressure, plasma BNP level, E/A ratio, E wave deceleration time, E/Ea ratio and the systolic pulmonary arterial pressure allowed prediction of the occurrence of acute decompensation following initiation and titration of bisoprolol. The use of the initial value of NYHA class alone allowed prediction of the occurrence of acute decompensation in just 56% of the patients, and the absence of an occurrence of acute decompensation in 93% of them. Normal results for the echocardiographic indices (systolic pulmonary arterial pressure<40 mmHg or E/A ratio<1.4 or E wave deceleration time>145 ms) as recorded on admission were associated with the absence of an occurrence of acute decompensation is 100% of cases. The combined use of NYHA class>3 and either a BNP>398 pg/ml or echocardiographic indices in favour of an elevation in left ventricular filling pressures (systolic pulmonary arterial pressure>40 mmHg, E/A ratio>1.4 or E wave deceleration time<145 ms) allowed prediction of the occurrence of acute heart failure in 100% of cases. The combined use of NYHA class, BNP level and echocardiographic indices for measuring left ventricular filling pressures is more pertinent than the isolated use of clinical parameters for predicting tolerance to bisoprolol in chronic heart failure with a LVEF<40%.

Topics: Adrenergic beta-Antagonists; Bisoprolol; Creatinine; Female; Heart Failure, Systolic; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography