ABSTRACT
BACKGROUND: Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure. METHODS AND RESULTS: Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP. CONCLUSIONS: In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.
Subject(s)
Cardiac Output, Low/blood , Cardiac Output, Low/mortality , Endothelin-1/blood , Aged , Cardiac Output, Low/physiopathology , Chronic Disease , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Natriuretic Peptide, Brain/blood , Osmolar Concentration , Prognosis , Proportional Hazards Models , Randomized Controlled Trials as Topic , Severity of Illness IndexABSTRACT
BACKGROUND: A deleterious effect of complete left bundle-branch block (LBBB) on left ventricular function has been established. Nevertheless, the independent effect of a widened QRS on mortality rate in congestive heart failure (CHF) is still controversial. Therefore, we carried out this analysis to determine whether LBBB is an independent predictor of mortality in CHF. METHODS AND RESULTS: We analyzed the large Italian Network on CHF Registry of unselected outpatients with CHF of different causes. The registry was established by the Italian Association of Hospital Cardiologists in 1995. Complete 1-year follow-up data were available for 5517 patients. The main underlying cardiac diagnosis was ischemic heart disease in 2512 patients (45.6%), dilated cardiomyopathy in 1988 patients (36.0%), and hypertensive heart disease in 714 patients (12.9%). Other causes were recorded in the remaining 303 cases (5.5%). LBBB was present in 1391 patients (25.2%) and was associated with an increased 1-year mortality rate from any cause (hazard ratio, 1.70; 95% confidence interval, 1.41 to 2.05) and sudden death (hazard ratio, 1.58; 95% confidence interval, 1.21 to 2.06). Multivariate analysis showed that such an increased risk was still significant after adjusting for age, underlying cardiac disease, indicators of CHF severity, and prescription of angiotensin-converting enzyme inhibitors and beta-blockers. CONCLUSION: LBBB is an unfavorable prognostic marker in patients with CHF. The negative effect is independent of age, CHF severity, and drug prescriptions. These data may support the rationale of randomized trials to verify the effects on mortality rate of ventricular resynchronization with multisite cardiac pacing in patients with CHF and LBBB.
