EFFECTS OF A NOVEL INOTROPIC AGENT (OPC-18790) ON SYSTOLIC AND DIASTOLIC FUNCTION IN PATIENTS WITH SEVERE HEART-FAILURE

A double-blind placebo-controlled study to determine the acute hemodynamic and cardiac mechanical effects of the quinolinone derivative OPC-18790 was performed in 12 patients with New York Heart Association class III or IV congestive heart failure. Simultaneous echocardiographic, Doppler, and invasive hemodynamic studies were performed before and after a 6-hour intravenous infusion of drug at 2.5, 5.0, or 10.0 mu g/kg/min or of placebo. OPC-18790 (mean dose 5.9 +/- 3.5 mg) caused significant increases in left ventricular (LV) ejection fraction (15% +/- 4% vs 23% +/- 5%; p < 0.05) and cardiac index (1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m(2); p < 0.05) and a rightward and upward shift in the stress-shortening relation. LV end-diastolic volume and heart rate were unchanged. LV filling and posterior LV wall thinning rates from digitized M-mode echocardiographic studies (0.49 +/- 0.16 vs 0.75 +/- 0.21 cm/sec and 2.0 +/- 0.9 vs 3.0 +/- 1.4 cm/sec, respectively; both p < 0.05), transmitral deceleration time (67 +/- 24 vs 81 +/- 19 msec, p < 0.05), and atrial filling fraction (31.0% +/- 11.2% vs 38.9% +/- 13.9%, p < 0.05) increased with OPC-18790 infusion. Despite a significant decrease in pulmonary capillary wedge pressure (28 +/- 9 vs 18 +/- 10 mm Hg) there was no change in the velocity-time integral of early diastolic filling (53 +/- 12 vs 59 +/- 22 cm), suggesting improved LV relaxation. Hemodynamics and parameters of LV function were unchanged in the 3 patients receiving placebo. We conclude that in addition to its positive inotropic effects, OPC-18790 may produce hemodynamic benefit by salutary effects on LV relaxation, atrioventricular compliance, and late ventricular diastolic filling.