Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: the PROPHET study.
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.
von Scheidt
Wolfgang
W
Klinikum Grosshadern, Medizinische Klinik I, University of Munich, Munich, Germany. w.scheidt.med1@klinikum-augsburg.de
Costard-Jaeckle
Angelika
A
Stempfle
Hans Ulrich
HU
Deng
Mario C
MC
Schwaab
Bernhard
B
Haaff
Bernd
B
Naegele
Herbert
H
Mohacsi
Paul
P
Trautnitz
Michael
M
D000328:Adult; D000527:Alprostadil; D006328:Cardiac Catheterization; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006084:Graft Rejection / Q000503:physiopathology; D016027:Heart Transplantation / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012737:Sex Factors; D013318:Stroke Volume / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D014665:Vasodilator Agents; D000527:Alprostadil