Dose dependence of chronic positive inotropic effect of vesnarinone in patients with congestive heart failure due to idiopathic or ischemic cardiomyopathy

Vesnarinone is a novel oral agent that improves survival and symptoms of patients with dilated cardiomyopathy. Although it is thought to have positive inotropic effects, clinical data supporting this mechanism in patients with severe heart failure remain scant. The present study tested whether 3 months of oral vesnarinone therapy increases the inotropic state and whether this response is dose dependent. Twenty-one patients with dilated cardiomyopathy (New York Heart Association class III to IV) were randomized to 30 mg/day (n = 11) or to 60 mg/day (n = 10) of vesnarinone. Cardiac function was assessed before and after therapy by radionuclide ventriculography to measure left ventricular volume and flow and by noninvasive measurement of the central aortic pressure wave. The inotropic effect of vesnarinone was assessed by a recently validated index equal to the ratio of left ventricular maximal ventricular power divided by the square of end-diastolic volume (PWR_max/ EDV²). This ratio is sensitive to inotropic change but is minimally altered by chamber loading. After 3 months of 60 mg/day therapy, PWR_max/EDV² increased by 28 ± 32%. Ejection fraction and cardiac output also increased by 21 ± 14% and 14 ± 14%, respectively, and arterial load decreased by 10.5 ± 12.4% (all p < 0.005). End-systolic volume also declined by 7 ± 10%, suggesting reverse remodeling. These changes were smaller and none achieved statistical significance at the 30 mg/day dose (e.g., 14.2 ± 35.4% for PWR_max/ EDV²). Heart rate was unchanged with either dose. Thus, chronic vesnarinone treatment dose modestly raises the inotropic state and lowers afterload in patients with dilated cardiomyopathy in a dose-dependent fashion.