DOES DIGOXIN PROVIDE ADDITIONAL HEMODYNAMIC AND AUTONOMIC BENEFIT AT HIGHER DOSES IN PATIENTS WITH MILD-TO-MODERATE HEART-FAILURE AND NORMAL SINUS RHYTHM

Objectives. This study sought to examine the hemodynamic and autonomic dose response to digoxin. Background. Previous studies have demonstra ted an increase in contractility and heart rate variability with digit alis preparations. However, little is known about the dose response to digoxin, which has a narrow therapeutic window. Methods. Nineteen pat ients with moderate heart failure and a left ventricular ejection frac tion <0.45 were studied hemodynamically using echocardiography and blo od pressure at baseline and after 2 weeks of low dose (0.125 mg daily) and 2 weeks of moderate dose digoxin (0.25 mg daily). Loading conditi ons were altered with nitroprusside at each study. Autonomic function was studied by assessing heart rate variability on 24-h Holter monitor ing and plasma norepinephrine levels during supine rest. Results. Low dose digoxin provided a significant increase in ventricular performanc e, but no further increase was seen with the moderate dose. Low dose d igoxin reduced heart rate and increased heart rate variability. Modera te dose digoxin produced no additional increase in heart rate variabil ity or reduction in sympathetic activity, as manifested by heart rate, plasma norepinephrine or low frequency/high frequency power ratio. In addition, we did not find that either low or moderate dose digoxin in creased parasympathetic activity. Conclusions. We conclude that modera te dose digoxin provides no additional hemodynamic or autonomic benefi t for patients with mild to moderate heart failure over low dose digox in. Because higher doses of digoxin may predispose to arrhythmogenesis , lower dose digoxin should be considered in patients with mild to mod erate heart failure. (C) 1997 by the American College of Cardiology.