PHYSIOLOGICAL ASSESSMENT OF MILRINONE THERAPY IN SEVERE HEART-FAILURE PATIENTS

To assess the inotropic, vasodilator, and after-load-reducing effects of intravenous milrinone in patients with severe congestive heart failure, a simple noninvasive echocardiographic study coupled with a right catheterization was performed in 12 patients. Milrinone was administered intravenously as a 50-mu-g.kg-1 bolus followed by a 24-h milrinone infusion at a rate of 5-mu-g.kg-1.min-1. Echocardiographic left ventricular end-diastolic diameter (D(ed)), end-systolic diamter (D(es)), and wall thickness were measured at baseline and at 24 h of milrionone infusion, before and after a sublingual nitrate administration (0.8 mg of nitroglycerin) that induced load variations. Hemodynamic measurements were performed simultaneously. Left ventricular end-systolic meridional wall stress (S(es)) was then calculated. The slopes of percent fractional shortening (percent FS)/S(es) and S(es)/D(es), obtained during sublingual nitrate administration, were traced. Both end-systolic relations are an index of the contractile state. Milrinone therapy improved hemodynamics in all patients, resulting in stabilized hemodynamic conditions between 12 and 24 h of continuous milrinone infusion. At these times, the cardiac index increased to 30% while the capillary pulmonary wedge pressure and systemic vascular resistance decreased to 26 and 24%, respectively (all p < 0.01). The average slope of S(es)/D(es) shifted upward from 47.5 +/- 30 to 69.25 +/- 34 (p < 0.05) and the average slope of (percent FS)/S(es) shifted from -0.032 +/- 0.025 to -0.082 +/- 0.061 (p < 0.01), both variations attesting the inotropic effect of milrinone. However, the decrease in systemic vascular resistance (DELTA-SVR) was closely correlated to the decrease in end-systolic meridional wall stress (DELTA-S(es)) (r = + 0.75; p = 0.0046). This suggests a dominant vasodilator action of milrinone in severe heart failure patients. This noninvasive echocardiographic study coupled with a right catheterization allowed the separation of the inotropic effect of milrinone from its vasodilator action. This may have useful clinical implications for intensive care patients with severe heart failure.