Patients with chronic heart failure frequently have pulmonary hypertension. Because severe preoperative pulmonary hypertension predicts a poor outcome after orthotopic transplantation, pulmonary vasoreactivity is evaluated frequently in the pretransplantation screening of heart failure patients. We prospectively evaluated the utility of the direct pulmonary vasodilator, prostaglandin E1, and compared it to the nonspecific vasodilators, nitroglycerin and sodium nitroprusside, in the evaluation of pulmonary hypertension in 39 heart transplantation candidates. Prostaglandin E1 significantly lowered pulmonary artery pressure, transpulmonary pressure gradient, and pulmonary vascular resistance. An adequate pulmonary vasodilator response (defined as a decline in transpulmonary pressure gradient to less than 15 mm Hg) occurred in 31 patients (79%). In a subgroup of nine patients also tested with nitroglycerin, greater reductions (p < 0.01) in both transpulmonary pressure gradient and pulmonary vascular resistance occurred with prostaglandin E1, compared to nitroglycerin. Five of six patients who did not respond to nitroglycerin responded to prostaglandin E1. In another subgroup of 12 patients who were also evaluated with sodium nitroprusside, prostaglandin E1 produced a larger decline (p < 0.05) in transpulmonary pressure gradient and pulmonary vascular resistance than did sodium nitroprusside. Six of eight patients who did not respond to sodium nitroprusside responded to prostaglandin E1. Based on pulmonary vasodilator response to prostaglandin E1, 27 patients were accepted on the transplantation waiting list, and eight patients underwent orthotopic transplantation. Postoperatively, acute right ventricular failure of the donor heart developed in none of these patients. Significant hemodynamic improvement occurred by 24 hours and persisted through 4 weeks of postoperative follow-up in all patients. In five patients prostaglandin E1 therapy was transiently needed after surgery to reverse pulmonary hypertension. These results suggest that prostaglandin E1 is superior to nitroglycerin and sodium nitroprusside in the pretransplantation evaluation of pulmonary vasoreactivity in patients with chronic heart failure. Further, this drug is also useful in the management of pulmonary hypertension after orthotopic transplantation.

Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Congestive heart failure patients with severe pulmonary hypertension are at risk of death from acute right ventricular failure of the donor heart in the early postoperative period after orthotopic cardiac transplantation. Therefore in the preoperative evaluation of these patients, it is extremely important to determine whether pulmonary hypertension can be reversed by pharmacologic means. Patients with reactive pulmonary hypertension can be considered suitable for orthotopic transplantation and the effective drug utilized postoperatively to reverse pulmonary hypertension and prevent failure of the donor right ventricle. To determine which pharmacologic agent is most effective in reversing pulmonary hypertension in congestive heart failure, the acute pulmonary hemodynamic effects of comparable doses of direct intravenous vasodilators including nitroglycerin, nitroprusside, and prostaglandin E1, and intravenous inotropic agents dobutamine and enoximone, were evaluated in 66 patients undergoing cardiac transplantation evaluation. All drugs significantly increased cardiac output and decreased calculated pulmonary vascular resistance. All drugs except dobutamine significantly lowered pulmonary artery and pulmonary artery wedge pressures. Prostaglandin E1 was the only drug that significantly lowered transpulmonary pressure gradient (pulmonary artery mean pressure minus mean pulmonary wedge pressure). The magnitude of decline of pulmonary vascular resistance and transpulmonary pressure gradient was greatest with prostaglandin E1 compared with other drugs. These observations indicate that prostaglandin E1 may be more effective than the other studied drugs for acute reversal of pulmonary hypertension in congestive heart failure.

Since impaired myocardial contractility is the primary deficit in a large number of patients with congestive heart failure (CHF), long-term treatment with oral positive inotropic agents has generated considerable interest over the last decade. A number of inotropic agents demonstrate salutary hemodynamic effects when administered short-term.1 Benefits of long-term therapy are, however, unclear.2,3 The dose of the inotropic agent may be crucial to its overall efficacy since serious side effects and even death may occur at high doses.4 In a wide range of doses, both intravenous and oral forms of enoximone (an experimental phosphodiesterase inhibitor) exert positive inotropic, chronotropic and vasodilator effects in chronic CHF patients.5,6 It has been shown that there is a plateau in the dose-effect relation of oral enoximone since doses in excess of 3.0 mg/kg do not offer any further hemodynamic benefit.7 Additionally, doses in the 3 to 6 mg/kg range appear to have a very high incidence of adverse side effects.8 The optimal dose of oral enoximone in chronic CHF is unknown. To determine whether the desirable and undesirable hemodynamic effects of oral enoximone are seen at different doses, we studied the short-term effects of various single doses (0.5 to 3.0 mg/ kg) of this drug in 65 patients with severe CHF.