EFFECT OF METOPROLOL ON MYOCARDIAL-FUNCTION AND ENERGETICS IN PATIENTS WITH NONISCHEMIC DILATED CARDIOMYOPATHY - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Objectives. This study examined the effects of metoprolol on left vent ricular performance, efficiency, neurohormonal activation and myocardi al respiratory quotient in patients with dilated cardiomyopathy. Backg round. The mechanism by which beta-adrenergic blockade improves ejecti on fraction in patients with dilated cardiomyopathy remains an enigma. Thus, we undertook an extensive hemodynamic evaluation of this mechan ism. In addition; because animal models have shown that catecholamine exposure may increase relative fatty acid utilization, we hypothesized that antagonism of sympathetic stimulation may result in increased ca rbohydrate utilization. Methods. This was a randomized, double blind, prospective trial in which 24 men with nonischemic dilated cardiomyopa thy underwent cardiac catheterization before and after 3 months of the rapy with metoprolol (n = 15) or placebo (n = 9) in addition to standa rd therapy. Pressure-volume relations were examined using a micromanom eter catheter and digital ventriculography. Results. At baseline, the placebo-treated patients had some what more advanced left ventricular dysfunction. Ejection fraction and left ventricular performance improv ed only in the metoprolol treated patients. Stroke and minute work inc reased without an increase in myocardial oxygen consumption, suggestin g increased myocardial efficiency. Further increases in ejection fract ion were seen between 3 and 6 months in the metoprolol group. The plac ebo group had a significant increase in ejection fraction only after c rossover to metoprolol. A significant relation between the change in c oronary sinus norepinephrine and myocardial respiratory quotient was s een, suggesting a possible effect of adrenergic deactivation on substr ate utilization. Conclusions. These data demonstrate that in patients with cardiomyopathy, metoprolol treatment improves myocardial performa nce and energetics, and favorably alters substrate utilization. Beta-a drenergic blocking agents, such as metoprolol, are hemodynamically and energetically beneficial in the treatment of myocardial failure.