EFFECT OF LOW-DOSE BETA-BLOCKERS ON ATRIAL AND VENTRICULAR (B-TYPE) NATRIURETIC FACTOR IN HEART-FAILURE - A DOUBLE-BLIND, RANDOMIZED COMPARISON OF METOPROLOL AND A 3RD-GENERATION VASODILATING BETA-BLOCKER

Objectives-This study examines the acute effects of two differing beta adrenergic blocking agents (metoprolol and a third generation vasodil ating beta blocker) on plasma concentrations of atrial natriuretic fac tor (ANF), brain (ventricular) natriuretic factor (BNF), and haemodyna mic variables in patients with heart failure. Setting-University teach ing hospital. Methods-20 patients with impaired left ventricular systo lic function [ejection fraction 32 (SEM 2.3)%] were randomised in a do uble blind manner to receive either oral metoprolol 6.25 mg twice dail y or celiprolol 25 mg daily. Haemodynamic variables were evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF concent rations were measured at baseline, 5 h, and 24 h by radioimmunoassay. Results-At baseline ANF and BNF concentrations were considerably raise d compared to the normal range. Treatment with metoprolol caused ANF t o rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was associated with a small but non-signific ant rise in pulmonary capillary wedge pressure. Cardiac output and sys temic vascular resistance were unchanged at 24 h. In contrast, after c eliprolol ANF fell to 90% of basal levels at 5 h and to 74% of basal l evel at 24 h (P = 0.019), associated with a small but non-significant fall in pulmonary capillary wedge pressure [-3.3 (2.7) mm Hg] and syst emic vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) 1/min (P = 0.04). BNF concentrations rose to 112% of baseli ne at 5 h (P 0.09) after metoprolol but fell slightly, to 91% of basel ine values, after celiprolol (NS). Conclusions-Metoprolol, even in ver y low doses (6.25 mg), produced a rise in ANF and BNF, although minima l haemodynamic changes were detected. In contrast, a vasodilating beta blocker was associated with a significant fall in ANF and BNF and a s mall rise in cardiac output. This study confirms both the advantages o f vasodilating beta blockers over metoprolol for initial treatment of heart failure and the usefulness of ANF and BNF measurements for the a ssessment of drug effects in heart failure compared to traditional hae modynamic measurements.