Pharmacological testing of the reversibility of increased pulmonary vascular resistance before heart transplantation with prostaglandin I2 (prostacyclin)

Abstract

An increased pulmonary vascular resistance (PVR) or an increased transpulmonary gradient (TPG) is a risk factor for increased 3-day and 3-month mortality after heart transplantation (HTx). The reversibility of increased PVR or TPG under pharmacologic testing is supposed to indicate a decreased probability of right ventricular failure/death after transplantation. We tested the response of an increased PVR (> 2.5 Wood units, WU) and/or of an increased TPG (> 15 mm Hg) in 29 right heart catheterizations (thermodilution catheter) of 23 patients (54 +/- 8 years, mean NYHA-class 3.1 +/- 0.6, ischemic n = 8, dilated cardiomyopathy n = 15). Increasing doses of prostaglandin I2 (PGI2, mean maximum dose 13.5 +/- 6.4 ng/kg/min) were applied stepwise over at least 10 min at the maximum dose level. We analyzed any dependence of the reversibility of PVR and TPG under prostaglandin I2 on hemodynamic values, echocardiographic parameters, demographic data, and laboratory findings. A decrease of PVR to a range usually accepted as no contraindication for HTx (< or = 4 WU) was found in each patient without symptomatic systemic hypotension during application of PGI2 (baseline value: 4.7 +/- 1.3 WU, during PGI2: 2.3 +/- 0.6 WU). An unresponsive, fixed increased PVR or TPG was not observed using PGI2. In 62% of investigations, both PVR and TPG decreased below 2.5 WU and 15 mmHg, respectively. The extent of reversibility of PVR and TPG was individually different and did not depend on the mean pulmonary artery pressure, mean capillary wedge pressure, cardiac output, mean systemic artery pressure or echocardiographic parameters (EDD, FS, ES-distance), sodium, urea or bilirubin levels, medication, age of the patients or the duration of the disease. The baseline PVR correlated inversely with its percentile value during PGI2 (r = -0.76, p < 0.05). In advanced heart failure, PGI2 decreases PVR in ranges of lower risk concerning orthotopic HTx, without causing an intolerable systemic hypotension. The individual extent of reversibility of PVR and TPG under PGI2 is not influenced by basic hemodynamic parameters or the patient's demographic profile.