Suppression of the Renin-Angiotensin System by Intravenous Digoxin in Chronic Congestive Heart Failure ANDREW 6. COVIT, M.D. GARY L. SCHAER, M.D. JEAN E. SEALEY, D.Sc. JOHN H. LARAGH, M.D. ROBERT J. CODY, M.D. New zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Yo rk, Ne w Yo rk From the Cardiovascular Center, Departments of Medicine and Pharmacology, New York Hospi- tal-Cornell University Medical Center, New York, New York. Requests for reprints should be ad- dressed to Dr. Robert J. Cody, Cardiovascular Center, Section J-3, New York Hospital-Cornell University Medical Center, 525 East 68th Street, New York, New York 10021. Manuscript accepted January 31, 1983. Recent studies have demonstrated that therapy with digitalis preparations may be of inconsistent benefit in the treatment of chronic congestive heart failure. One explanation may be a varying effect on vasoconstrtctor hormones, as digoxin has been shown to suppress plasma renin activity in normal and hypertensive persons. Therefore, the effect of short-term digoxin administration on plasma renin activity and plasma aldosterone in six patients with compen- sated, severe, chronic congestive heart failure was evaluated. In- travenous administration of digoxin (0.50 mg) resulted in a reduction of plasma renin activity from 4.3 f 0.9 to 2.0 f 0.9 ng/ml per hour and plasma aldosterone from 34 f 16 to 14 f 6 ng/dl (both p <0.05). Maximal response occurred at three hours after adminis- tration, with return to baseline by seven hours. Therefore, evaluation of the role of digitalis in chronic heart failure requires consideration of its direct or indirect effect on angiotensin-mediated vasocon- striction and aldosterone-mediated sodium retention, as well as other neurohormonal mechanisms of vasoconstriction. Recent data indicate that digoxin therapy is not uniformly beneficial in patients with chronic congestive heart failure [ 1,2]. Furthermore, the mechanism by which edema is relieved by digoxin has not been adequately explained. In this regard, previous studies have demon- strated that the short-term administration of digoxin to normal [3] and hypertensive patients [4] results in a reduction in plasma renin activity. This hormonal effect of digoxin has not been explored in patients with chronic heart failure, wherein increased plasma renin activity results in angiotensin-mediated vasoconstriction and aldosterone-mediated sodium retention in many patients [5,6]. We therefore investigated the effect of acute digoxin administration on plasma renin activity and aldosterone in patients with severe, chronic congestive heart failure. PATIENTS AND METHODS This study consisted of six patients with severe, chronic congestive heart failure, ranging in age from 42 to 76 years. There were four men and two women. All patients had functional class Ill or IV New York Heart Association symptoms, and all were hospitalized at least three days before the study. Before entry into the study, all digitalis preparations were discontinued for at least two weeks, and vasodilator therapy had been discontinued for at least five days. Two patients continued to receive diuretic therapy because of the severity of their disease, but did not receive diuretics in the 12 hours before the study. Patients were studied in the supine position in the morning after an over- night fast. An indwelling, multi-sample catheter was placed in an arm vein September 1993 The American Journal of Medlclne Volume 75 445