EFFECTS OF INCREASING MAINTENANCE DOSE OF DIGOXIN ON LEFT-VENTRICULARFUNCTION AND NEUROHORMONES IN PATIENTS WITH CHRONIC HEART-FAILURE TREATED WITH DIURETICS AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

Background Despite almost three centuries of use, the appropriate dosa ge of digitalis in patients with chronic heart failure and normal sinu s rhythm has not been well studied. Methods and Results We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics; and angiotensin-converting enzyme (ACE) inhibitor s. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20+/-0.07 to 0.39+/-0.11 mg/day corresponding to an increas e in the serum digoxin concentration from 0.67+/-0.22 to 1.22+/-0.35 n g/mL. Radionuclide and echocardiographic left ventricular ejection fra ction; maximal treadmill time; heart failure score; serum concentratio ns df norepinephrine, aldosterone, atrial natriuretic factor, and anti diuretic hormone; and plasma renin activity were obtained before and a fter the increase in digoxin dose. Subsequently, 9 patients were rando mized to receive digoxin and 9 to receive placebo and radionuclide eje ction fraction measured after 12 weeks. With the higher dose of digoxi n compared with the lower dose, there was a significant increase in ra dionuclide ejection fraction from 23.7+/-9.6% to 27.1+/-11.8% (P=.007) . No significant changes were noted in heart failure score exercise to lerance; serum concentrations of norepinephrine, atrial natriuretic fa ctor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, ther e was a significant decrease in ejection fraction (from 29.4+/-10.4% t o 23.7+/-8.9%) in the placebo group but not in patients who continued to receive digoxin (P=.002). Conclusions The increase in maintenance d igoxin dose, while maintaining serum concentrations Within therapeutic range, resulted in a significant increase in left ventricular ejectio n fraction that was not associated with significant changes in heart f ailure score, exercise tolerance, and neurohumoral profile.