Prognostic power of neurohumoral parameters in chronic heart failure depends on clinical stage and observation period

Background: Endothelin (ET) and natriuretic peptides have prognostic significance in chronic heart failure (CHF). Because stimuli for forming these neurohormones differ, this study investigates whether their prognostic power depends on clinical stage and on length of the observation period. Methods: Plasma big ET, B-type natriuretic peptide (BNP), N-terminal BNP (N-BNP), and N-terminal atrial natriuretic peptide (N-ANP), in addition to 11 clinical and hemodynamic variables, were obtained from 452 patients with left ventricular ejection fraction (LVEF) less than or equal to35%. According to their New York Heart Association class and LVEF, patients were stratified into Group A, mild CHF (n = 114); Group B, moderate CHF (n = 210); and Group C, severe CHF (n = 128). To predict the combined end-point of death or urgent heart transplantation, a multivariate analysis was performed after an observation period of up to 1, 2, and 3 years in all patients and in each subgroup. Results: Best independent predictors were as follows: All patients: up to 1 year, big ET (p < 0.0001, chi-square = 59); and 2 and 3 years, log N-ANP (p < 0.0001, chi-square = 68; p < 0.0001, chi-square = 89). Group A: up to 2 and 3 years, log N-ANP (P < 0.001, chi-square = 12; p < 0.0001, chi-square = 25). Group B: up to 1 and 3 years, log N-ANP (p < 0.0001, chi-square = 16; p < 0.0001, chi-square = 22); and 2 years, log N-BNP (p < 0.0001, chi-square = 19). Group C: up to 1, 2, and 3 years, big ET (P < 0.0001, chi-square = 23; p < 0.0001, chi-square = 22; p < 0.0001, chi-square = 20). Conclusion: Big ET was the best independent marker for 1-year prognosis in severe CHF, whereas natriuretic peptides (especially N-ANP) were better markers for 2- and 3-year prognoses in mild and moderate CHF.