Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction

Objectives The study assessed the relative predictive potency of neurohumor al factors in patients with advanced left ventricular (LV) dysfunction duri ng neurahumoral blocking therapy. Background The course of heart failure is characterised by progressive LV d eterioration assoc-fated with an increase in cardiac (natriuretic peptides) and predominantly extracardiac (norepinephrine, big endothelin [big ET]) h ormone plasma levels. Methods Plasma hormones were measured at baseline and months 3, 6, 12 and 2 4 in 91 patients with heart failure (left ventricular ejection fraction [LV EF] <25%) receiving 40 mg enalapril/day and double-blind atenolol (50 to 10 0 mg/day) or placebo. After the double-blind study phase, patients were fol lowed up to four years. Stepwise multivariate regression analyses were perf ormed with 10 variables (age, etiology, LVEF, symptom glass, atenolol/place bo, norepinephrine, big ET, log aminoterminal atrial natriuretic peptide, l og aminoterminal B-type natriuretic peptide [N-BNP] and log B-type natriure tic peptide [BNP]). During the study, the last values prior to patient deat h were used, and in survivors the last hormone level, New York Heart Associ ation class and LVEF at month 24 were used. Results Thirty-one patients died From a cardiovascular cause during follow- up. At baseline, log BNP plasma level (x(2) = 13.9, p = 0.0002), treatment allocation (x(2) = 9.5, p = 0.002) and LVEF (x(2) = 5.6, p = 0.017) were in dependently related to mortality. During the study, log BNP plasma level (x (2) = 21.3, p = 0.0001) remained the strongest predictive marker, with LVEF (x(2) = 11.2, = 0.0008) log N-BNP plasma level (x(2) = 8.9, p = 0.0027) an d treatment allocation (x(2) = 6.4 p = 0.0109) providing additional indepen dent information. Conclusions In patients with advanced LV dysfunction receiving high-dose an giotensin-converting enzyme inhibitors and beta-blocker therapy BNP and N-B NP plasma Levels are bath independently related to mortally. This observati on highlights the importance of these hormones and implies drat they will l ikely emerge as a very useful blood test for detection of the progression o f heart failure, even in the face of neurohumoral blocking thcrapy. (J Am C ell Cardiol 2001;38:436-42) (C) 2001 by the American College of Cardiology.