Medium-term effects of beta-blockade on left ventricular mechanics: a double-blind, placebo-controlled comparison of nebivolol and atenolol in patients with ischemic left ventricular dysfunction

Abstract

The aim of this study was to compare the effects on left ventricular function and exercise tolerance of a selective beta-antagonist (atenolol) with those of another selective beta 1-antagonist with vasodilator properties (nebivolol) in patients with ischemic left ventricular dysfunction but no overt congestive heart failure. Beta blockers are widely used in ischemic heart disease, but their effects on left ventricular mechanics and exercise tolerance are poorly defined in the subgroup of patients with significant systolic dysfunction but without clinical evidence of ischemia or congestive heart failure. Angiographic and symptom-limited exercise data were obtained at baseline and after an 8-10-week double-blind treatment with placebo (n = 10), 50 mg atenolol daily (n = 10), or 2.5 mg (n = 10) or 5 mg (n = 10) nebivolol daily. When compared to placebo, both atenolol and nebivolol reduced resting heart rate and improved left ventricular ejection fraction (from 33.9 to 39.2% with atenolol and from 36.5 to 40.8% with nebivolol, both P < .05) while lowering mean systolic wall stress. Only nebivolol, however, produced a parallel downward shift of the pressure-volume relationship during early diastolic filling and improved the early peak filling rate when compared to placebo (+ 10%, P < .05). When compared to baseline, maximal exercise duration increased by 7 and 13 seconds with placebo and atenolol, respectively (both NS vs baseline), and increased by 44 seconds with nebivolol (P = .0077 vs baseline). Both atenolol and nebivolol decreased maximal exercise heart rate; the reduction was more pronounced with atenolol. Prolonged beta 1-adrenoceptor blockade leads to a significant increase in left ventricular ejection fraction in patients with ischemic left ventricular dysfunction. The dissociation between the changes in resting left ventricular function and the changes in exercise duration suggests that in this clinical setting, the changes in systolic function may have less impact on functional capacity than an improvement in diastolic distensibility during the rapid filling phase.