Effect of oral milrinone on end-systolic relations in patients with severe congestive heart failure

Abstract

The new inotropic agent milrinone has both vasodilator and inotropic cardiovascular effects, but the importance of these effects in patients with severe congestive heart failure (CHF) is controversial. The left ventricular (LV) end-systolic pressure-diameter relation was used to determine the independent inotropic effect of milrinone. Seven patients with New York Heart Association class III CHF were invasively monitored with right-sided heart catheters and radial arterial lines. M-mode echocardiography was used to measure LV dimensions. The effect of a 10mg oral dose of milrinone on hemodynamic, echocardiographic and end-systolic variables was determined. End-systolic pressure was measured at the dicrotic notch of the arterial pressure tracing and end-systolic LV dimensions at the time of aortic valve closure. Methoxamine (n = 6) or nitroprusside (n = 1) was used to alter afterload so that the end-systolic pressure-diameter relation could be determined. Arterial vasodilation from milrinone was evidenced by a decrease in mean arterial blood pressure (88 ± 5 to 77 ± 2 mm Hg, p <0.025) and an increase in cardiac index (from 2.7 ± 0.2 to 3.2 ± 0.2 liters/min/m 2, p <0.025), with no change in heart rate (80 ± 5 beats/min). Milrinone decreased preload as assessed by the pulmonary artery wedge pressure (from 17 ± 2 to 10 ± 2 mm Hg, p <0.01) and end-diastolic LV diameter (from 7.4 ± 0.4 to 7.0 ± 0.4 cm, p <0.025). Milrinone caused decreases in the end-systolic pressure (from 79 ± 5 to 68 ± 2 mm Hg, p <0.01) and end-systolic LV diameter (from 6.6 ± 0.4 to 6.1 ± 0.5 cm, p <0.025). Milrinone treatment decreased end-systolic afterload as measured by end-systolic wall stress (from 106 ± 12 to 81 ± 12 g/cm 2, p <0.005), but resulted in no corresponding change in percent fractional shortening (13 ± 1 vs 13 ± 2%) or in rate-corrected velocity of circumferential fiber shortening (0.45 ± 0.05 vs 0.43 ± 0.06 circ/s). The slope of the end-systolic pressure-diameter relation was not significantly different at control (37 ± 6 mm Hg/cm) than at peak milrinone effect (46 ± 11 mm Hg/cm), nor was there a significant change in the diameter intercept (3.9 ± 0.7 vs 4.1 ± 0.7 cm). The range of pressure and diameter values over which the end-systolic pressure-diameter relation was determined, however, was limited by the markedly abnormal LV function and cardiovascular status of these patients. In conclusion, during acute oral therapy in patients with severe CHF, the predominant effect of milrinone as assessed by end-systolic relations is as a vasodilator and not as a positive inotropic agent.