Clinical heart transplantation
Prostaglandin E1 Testing in Heart Failure–associated Pulmonary Hypertension Enables Transplantation: The PROPHET Study

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Background

Elevated pulmonary vascular resistance (PVR) is relevant to prognosis of congestive heart failure and heart transplantation. Proof of reversibility by pharmacologic testing in potential transplantation candidates is important because it indicates a reduced probability of right ventricular failure or death in the early post-transplant period. This study aimed to clarify the possible extent of acute reversibility of elevated PVR in a large, consecutive cohort of heart transplant candidates.

Methods

This study included 208 consecutive patients (age 52 ± 10 years, 89% men and 11% women, ejection fraction 21 ± 9%, Vo2max 12.6 ± 4.2 ml/kg/min) being evaluated for heart transplantation in 7 transplant centers in Germany and Switzerland. Testing was performed with increasing intravenous doses of prostaglandin E1 (PGE1; average maximum dose 173 ± 115 ng/kg/min for at least 10 minutes) in 92 patients exhibiting a baseline PVR of >2.5 Wood units (WU) and/or a transpulmonary gradient (TPG) of >12 mm Hg.

Results

PGE1 testing lowered PVR from 4.1 ± 2.0 to 2.1 ± 1.1 WU (p < 0.01), increased cardiac output from 3.8 ± 1.0 to 5.0 ± 1.5 liters/min (p < 0.01), and decreased TPG from 14 ± 4 to 10 ± 3 mm Hg (p < 0.01), mean pulmonary artery pressure (PAM) from 39 ± 9 to 29 ± 9 mm Hg (p < 0.01) and mean pulmonary capillary wedge pressure (PCWP) from 24 ± 7 to 19 ± 9 mm Hg (p < 0.01). Mean aortic pressure (MAP) decreased to 85% and systemic vascular resistance (SVR) to 65% of baseline values (p < 0.01). Symptomatic systemic hypotension was not observed. For the whole population the percentage of patients with PVR >2.5 WU was reduced from 44.2% to 10.5% with PGE1. PVR decreased in each patient; only 2 patients (1%) remained ineligible for listing because of a final PVR of >4.0 WU. TPG, ejection fraction and male gender were independent predictors of reversibility of PVR.

Conclusions

Elevated PVR in heart transplant candidates is highly reversible and can be normalized during acute pharmacologic testing with PGE1.

Section snippets

Population

The study included 208 consecutive heart failure patients undergoing evaluation for potential listing for heart transplantation (Table 1). Patients dependent on intravenous inotropic support were excluded. The study was approved by the ethics committee of each participating study center. Written informed consent was given by each patient.

Right Heart Catheterization and Testing With PGE1

All 208 patients underwent right heart catheterization while under continuation of their pre-existing oral therapy (Table 1), which was not changed before and

Baseline Hemodynamics

The baseline hemodynamics of the entire population (n = 208) and the pre-defined patient cohorts without (n = 116) and with (n = 92) increased PVR >2.5 WU or TPG >12 mm Hg are given in Table 2.

PGE1 Testing

In the 92 patients tested with PGE1, PVR decreased from 4.1 ± 2.0 to 2.1 ± 1.1 WU (p < 0.01), and TPG from 14 ± 4.0 to 10 ± 3.0 mm Hg (p < 0.01). CO increased from 3.8 ± 1.0 to 5.0 ± 1.5 liters/min (p < 0.01). PAM decreased from 39 ± 9 to 29 ± 9 mm Hg (p < 0.01), and mean PCWP from 24 ± 7 to 19 ± 9 mm Hg (p

Effectiveness of PVR Reversibility Testing and Implications for Transplant Listing

This multicenter study demonstrates the reversibility of increased PVR with PGE1 in a large cohort of patients with severe left ventricular dysfunction being evaluated for orthotopic heart transplantion. At baseline, 92 of 208 patients (44%) exhibited a PVR >2.5 WU, and 37 of 208 (18%) a PVR >4.0 WU (a consensus cut-off value for ineligibility for heart transplant listing in Germany11). After PGE1 testing PVR remained >2.5 WU in only 22 of 208 patients (10.6%), and only 2 of 208 patients (1%)

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    Supported by Pharmacia-Upjohn (Nuernberg, Germany).

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