Bridging to heart transplantation: prostaglandin E 1 versus prostacyclin versus dobutamine

Abstract

Background: Prostaglandin E 1 (PGE 1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE 1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. Methods Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index ≤2.5 L/minute/m 2 and a pulmonary capillary wedge pressure ≥20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm −5m −2. During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. Results Sixty-eight patients were enrolled, 30 patients on PGE 1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 ± 1.8 ng/kg/minute for PGE 1, 7 ± 1 ng/kg/minute for prostacyclin and 5 ± 0.4 μg/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE 1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine ( p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE 1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 ± 14 days in the PGE 1 group with 31 ± 22 days in the prostacyclin group, and 30 ± 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE 1, 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine ( p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. Conclusions The findings from this prospective open pilot trial suggest that continuous PGE 1 infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE 1 among other bridging agents.