Effect of Bolus Milrinone on Hemodynamic Variables and Pulmonary Vascular Resistance in Patients With Severe Left Ventricular Dysfunction: A Rapid Test for Reversibility of Pulmonary Hypertension

Abstract

To examine the feasibility of using milrinone to test pulmonary vascular reactivity in patients before heart transplantation, we tested the hypothesis that milrinone would lower pulmonary vascular resistance (PVR) in patients with severe heart failure. Fixed pulmonary hypertension is a risk factor for right heart failure and death after orthotopic heart transplantation. Sodium nitroprusside, the agent used most commonly to test for reversibility of pulmonary hypertension before transplantation, requires dose titration and is frequently limited by hypotension. Milrinone is an intravenously active phosphodiesterase inhibitor that acts rapidly and exerts both positive inotropic and direct vasodilator effects in patients with heart failure. The ability of milrinone to lower PVR in patients with heart failure has not been tested. In 27 patients with New York Heart Association functional class III or IV heart failure referred for heart transplantation with a PVR > or = 200 dynes-s-cm-5, we measured the hemodynamic response to a single intravenous bolus of milrinone (50 micrograms/kg body weight) infused over 1 min. Milrinone decreased PVR in all patients. The effect was maximal 5 to 10 min after the bolus and persisted for at least 20 min. The reduction in PVR at 5 min ([mean +/- SEM] 31 +/- 4%) was associated with a 42 +/- 4% increase in cardiac output and decreases of 12 +/- 4% and 16 +/- 5% in mean pulmonary artery and pulmonary artery wedge pressures, respectively, but no change in transpulmonary pressure gradient. Milrinone had no effect on heart rate or systemic arterial pressure. The magnitude of the decrease in PVR correlated inversely with the milrinone-induced increase in cardiac output. Bolus milrinone consistently decreases PVR in patients with pulmonary hypertension secondary to severe heart failure. This effect is rapid in onset and well tolerated, even by patients with low systemic arterial pressure. An intravenous bolus of milrinone can be used to test for the reversibility of pulmonary hypertension in patients with heart failure undergoing evaluation for heart transplantation.