LONG-TERM (3-MONTH) EFFECTS OF AN NEW BETA-BLOCKER (NEBIVOLOL) ON CARDIAC-PERFORMANCE IN DILATED CARDIOMYOPATHY

Objective: This study examined the long-term (3-month) effects of nebi volol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy, Background Several beta-blockin g drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a place bo-controlled randomized study have addressed the mechanisms of improv ement, Methods: Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were ent ered into a double-blind randomized trial of nebivolol, a new potent, selective beta(1)-antagonist, Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered ne bivolol (1 to 5 mg/day, n = 11) or placebo (n = 13), Results: Heart ra te decreased (group mean 85 to 71 beats/min vs, 87 to 87 beats/min wit h placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs, 42 to 43 ml) with nebivolol; decreases in systemic resistan ce, systemic arterial pressure, wedge pressure and pulmonal artery pre ssure were not significantly different from those with placebo, Simila r hemodynamic results were obtained in the catheterization laboratory, Analysis of high fidelity measurements of left ventricular pressure s howed a decrease in left ventricular end-diastolic pressure in the neb ivolol group (group mean 21 to 15 vs, 24 to 20 mmHg with placebo) but no change in the maximal rate of pressure development or in two variab les of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dt(max)] and the time constant tau), Le ft ventricular mass decreased (p = 0.04), Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular e nd-diastolic volume (p = NS), End-systolic volume tended to decrease ( p = 0.07) despite no reduction in end-systolic stress, The net result was a significant increase in ejection fraction (group mean 0.23 to 0. 33 vs, 0.21 to 0.23 with placebo), presumably as a result of an increa se in contractile performance, This effect was corroborated by an incr ease in a relatively load-independent variable of myocardial performan ce, Conclusions: Nebivolol improved stroke volume, ejection fraction a nd left ventricular end-diastolic pressure, not through a measurable r eduction in afterload or a lusitropic effect, but by improving systoli c contractile performance.