Direct comparison between endothelin-1, N-terminal proatrial natriuretic factor, and brain natriuretic peptide as prognostic markers of survival in congestive heart failure.

Endothelin-1 (ET-1) and cardiac natriuretic peptide plasma concentrations have prognostic significance in congestive heart failure (CHF). However, their respective prognostic values in this setting have never been directly compared. We studied the prognostic performances of ET-1, N-terminal proatrial natriuretic factor (N-proANF), and brain natriuretic peptide (BNP) to predict the long-term cardiac mortality in fully treated patients with CHF. Peripheral plasma concentrations of the 3 peptides were measured in 109 patients (left ventricular ejection fraction [LVEF] < 35%) in New York Heart Association (NYHA) functional classes II (n = 65) or III to IV (n = 44). The outcome of the patients was evaluated 3 years after the beginning of the study, and a Cox regression model was used to identify predictors of death. Plasma concentrations of the 3 peptides increased with the severity of heart failure. By univariate analysis, 6 parameters were significantly associated with death during follow-up: ET-1 level, NYHA classes III to IV, N-proANF level, BNP level, LVEF, and age (all P < .01). By multivariate analysis, only ET-1 level and, to a lesser extent, N-proANF level contributed significantly and independently to risk stratification (chi2 = 53.4 and 12.8; P < .0001 and P < .001, respectively). In a group of patients in whom the vast majority were administered angiotensin-converting enzyme inhibitor therapy, plasma ET-1 and N-proANF concentrations identify better than several clinical markers a very high-risk group, fairly amenable to heart transplantation or new therapies.