From the Heart and Hypertension Department, Research Institute of the Cleveland Clinic Foundation, Cleveland, Ohio. Requests for reprints should be addressed to Dr. Fetnat M. Fouad-Taraii, Heart and Hypertension Department, Research Institute of the Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. It has been years since converting enzyme inhibitors were introduced for the treatment of congestive heart failure. Their effectiveness has been demonstrated in multiple reports that have shown improvement in hemodynamic indexes as well as clinical symptoms and quality of life [l-IO]. Moreover, this improvement generally lasted months or years. Our experience in this respect is summarized in Table I. We have studied 14 patients with congestive heart failure of ischemic or cardiomyopathic etiology, before and after captopril therapy, and obtained hemodynamic data at regular intervals over one year. These studies showed that cardiac output and stroke volume increased significantly in association with normalization of pulmonary mean transit time, reduction of plasma aldosterone, and some reduction in both plasma catecholamine levels and heart rate. These effects occurred within one week and were sustained. Changes in ejection fraction, however, were minimal compared with the significant reduction in mean transit time (Figure 1) probably because ejection fraction depends on left ventricular geometry in addition to loading conditions on the heart. Along with these hemodynamic findings, improvement in severity of heart failure (NYHA class) and its other clinical manifestations has been described in patients treated with converting enzyme inhibitors by Dzau et al [7], Levine et al [8], and others. Goldstein and Pitt [l l] also demonstrated that, compared with placebo and with digoxin, captopril treatment of heart failure resulted in significantly improved exercise duration, a 45 percent reduction of ventricular premature beats, and a reduction in frequency of hospitalization. The mechanism by which converting enzyme inhibitors maintain improvement is still not well understood. Several possibilities include: (1) the persistent beneficial hemodynamic effects of converting enzyme inhibition o’n afterload and preload; (2) persistent suppression of plasma aldosterone; (3) interference with the effects of angiotensin II on the renal tubules; and (4) a direct effect of accumulated angiotensin I on the heart v21. Compared with other vasodilators, captopril has been found to be more effective in improving effort tolerance in association with a more marked reduction in blood pressure and pulmonary mean transit time and a more marked increase in cardiac output [13]. These findings indicated that the hemodynamic changes induced by converting enzyme inhibitors are not the only factors mediating the long-term control of congestive heart failure during therapy. Moreover, tolerance to therapy was observed with other vasodilators but did not develop when captopril was used for a similar duration, suggesting that additional effects of converting enzyme inhibitors should be considered. For example, humoral studies in these pa-