The use of milrinone in pre-transplant assessment of patients with congestive heart failure and pulmonary hypertension

Background: Pulmonary hypertension in patients with congestive heart failure (CHF) is a risk factor for increased mortality after orthotopic cardiac transplantation. Reversibility of elevated pulmonary vascular resistance (PVR) by pharmacologic agents predicts improved outcomes. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, has been shown to lower PVR in one previous study. However, no study has documented outcomes after cardiac transplantation in patients in whom reversibility of pulmonary hypertension was demonstrated after administration of milrinone. Methods: We retrospectively reviewed 19 patients with CHF and pulmonary hypertension defined as PVR greater than or equal to 3 Wood units, PVRI (pulmonary vascular resistance index) greater than or equal to 4 resistance units, or TPG (transpulmonary gradient = mean pulmonary artery pressure - mean capillary wedge pressure) greater than or equal to 12 mmHg being assessed for cardiac transplantation. A sub-group of 14 patients with severe pulmonary hypertension defined as PVR greater than or equal to 4, PVRI greater than or equal to 6 and TPG greater than or equal to 15 was also examined. Milrinone was administered as a bolus (50 ug/kg) and hemodynamic parameters were measured at 5, 10 and 15 minutes. Six patients received cardiac transplants. Results: Administration of milrinone significantly lowered PVR, PVRI, mean pulmonary artery pressure (PAM) (all p = 0.002) and pulmonary capillary wedge pressure (PCWP) (p = 0.006). Cardiac output (CO) increased significantly (p = 0.001). TPG did not change (p = 0.33). In patients with severe pulmonary hypertension, the magnitude of these changes was greater. In addition, TPG was significantly lowered (p = 0.02). Conclusion: Milrinone lowered PVR by decreasing PAM and increasing CO significantly. In addition, PCWP was significantly lowered. These finding confirm both vasodilatory and inotropic effects of milrinone. Patients with severe pulmonary, hypertension had more pronounced effects. There were no deaths in the group of patients proceeding to cardiac transplantation. Our study demonstrates the efficacy of milrinone in lowering PVR as well as suggesting safety in use in patients undergoing cardiac transplantation.