Enoximone as a bridge to heart transplantation: the Utah experience

For the past several years, the UTAH Cardiac Transplant Program has been investigating the use of enoximone, a phosphodiesterase inhibitor with unique properties, as an oral pharmacologic adjunct to conventional management of severe congestive heart failure in patients awaiting heart transplantation. The goal of this approach is not long-term survival, but the ability to maintain patients comfortably with adequate tissue perfusion until the donor heart becomes available. Enoximone exhibits both positive inotropic and vasodilator characteristics. It appears to be the only agent that produces positive inotropic effects by phosphodiesterase inhibition alone, and its effects appear to last significantly longer than those of beta-adrenergic agonists. The results of the program's clinical experience with 281 patients suggest that inotropic support with low-dose enoximone may be a useful adjunct in the short-term management of patients with severe end-stage congestive heart failure. Almost 25% of patients who had been dependent on intravenous inotropic support were able to be weaned from intravenous therapy and switched to oral enoximone. No acceleration in mortality while patients awaited transplantation was observed. The data also showed an increase in the beta 2-adrenergic receptors and a difference in the beta 1:beta 2-receptor subtype ratio of 56:42 with enoximone, compared with 65:35 in a group of failing control patients who received no enoximone. In addition, the combination of enoximone and beta-adrenergic agonists was not associated with beta-receptor down-regulation.