Prostaglandin E1--bridge to cardiac transplantation. Technique, dosage, results.
BACKGROUND
Heart transplantation candidates who remain severely symptomatic despite therapy are normally hospitalized. Continuous infusion of intravenous drugs from a portable pump may allow such patients to live a fairly active life until a donor heart is found.


OBJECTIVE
To investigate in an open pilot study if heart transplantation can be safely accomplished if these patients are continuously bridged with various regimens including inotropic support with low-dose dobutamine in conjunction with dopamine and prostaglandin E1.


METHODS
We report on 5 years' experience with prostaglandin E1, a potent vasodilator with proven efficacy in severe heart failure when coupled with catecholamines. From 1990 to 1995 54 heart transplantation candidates were bridged with prostaglandin E1 in addition to dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 (group A; n = 32) or in addition to 3 micrograms.kg-1 min-1 dopamine alone (group B; n = 22), and 11 heart transplantation candidates were bridged with dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 only (group C; n = 11). In an initial dose-ranging test, prostaglandin E1 was uptitrated to side effect limit (29 +/- 1 ng.kg-1.min-1). Haemodynamics, except for stroke volume index, were similar in all patients at baseline and a sufficient haemodynamic response (20% increase in stroke volume) was observed during the acute study. Fifty percent of the peak dose was used for initiating chronic therapy; the dose of prostaglandin E1 was further reduced if side effects recurred.


RESULTS
Twenty-nine (54%) patients in groups A and B and six in group C could be discharged home with chronic therapy via a Hickman catheter connected to a portable pump. After 4 weeks in six patients in group A and in 13 patients in group B, when prostaglandin E1 had been reduced from 15 +/- 2 ng.kg-1.min-1 to 8 +/- 1 ng.kg-1 min-1 increases in cardiac index and decreases in systemic vascular resistance were sustained, and a permanent decrease in pulmonary vascular resistance index was observed in group B. Intravenous therapy was changed in nine patients (3/1/5) because of side effects and worsening heart failure. Prostaglandin E1 was withdrawn in three of these patients because of an increase in serum creatinine (3 mg.100 ml-1), and in one because of noncompliance. In total, there were 17 cardiac deaths (9/6/2), 42 heart transplants (22/14/6) and six (1/2/3) weaned survivors (including one non-cardiac death) in this study. Overall outcome was similar in groups A and B, but distribution after 2 months appeared to be different (P < 0.05) based on more transplantations in group A.


CONCLUSIONS
We concluded that chronic infusions with prostaglandin E1 at reduced dosages is a feasible and safe therapeutic adjunct to bridge end-stage heart failure patients and may yield desirable effects in a subset of patients in the absence of inotropic support by dobutamine.
Pacher
R
R
University of Vienna Department of Cardiology, Austria.
Stanek
B
B
Hülsmann
M
M
Berger
R
R
Siegel
A
A
Daneschvar
H
H
Rödler
S
S
Frey
B
B
Grimm
M
M
Laufer
G
G
D000527:Alprostadil / Q000008:administration & dosage* / Q000009:adverse effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002408:Catheters, Indwelling; D002908:Chronic Disease; D018450:Disease Progression; D004280:Dobutamine / Q000008:administration & dosage / Q000009:adverse effects; D004298:Dopamine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012449:Safety; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D002316:Cardiotonic Agents; D014665:Vasodilator Agents; D004280:Dobutamine; D000527:Alprostadil; D004298:Dopamine