RENAL HEMODYNAMIC-EFFECTS IN PATIENTS WITH MODERATE TO SEVERE HEART-FAILURE DURING CHRONIC TREATMENT WITH TRANDOLAPRIL

Treatment of patients with severe heart failure by ACE inhibition is o ften limited by worsening of renal function. To evaluate whether trand olapril, a potent lipophilic ACE inhibitor, affects renal function in severe heart failure, we studied 12 patients with severe heart failure treated with only diuretics and digoxin. Patients received increasing oral dosages of trandolapril (0, 1, and 2 mg) on 3 consecutive days ( A). Patients were then discharged on 2 mg trandolapril bid and re-eval uated 8 weeks later (B). Mean arterial and pulmonary wedge pressures d ecreased by maximal 14% and 43%, and stroke volume and work indexes in creased by 24% and 20% at A and similarly at B (11, 45, and 25 ns and 33%, respectively). In contrast, heart rate, systemic resistance, pulm onary artery pressure, and cardiac index decreased by 6%, 23%, 29%, an d 17%, respectively, at only A. Renal blood flow improved by approxima tely 40% both at A and B. In contrast, the glomerular filtration rate decreased by 25% at only B, whereas serum creatinine, creatinine clear ance, and urine osmolality were unaffected during the study. Norepinep hrine, angiotensin II, and aldosterone levels decreased by approximate ly 30%, 60%, and 65%, respectively, at both A and B. Renin levels incr eased by 136% at A and remained elevated at B. Thus, whereas the initi al systemic vasodilating and inotropic effects did not persist, long-t erm trandolapril results in sustained neurohormonal modulation, reduce d preload, and improved organ perfusion, indicated by a persistent inc rease in renal blood flow and preservation of renal function in severe heart failure.