Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure

Objectives. This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure. Background. Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed. Methods. We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy. Results. After digoxin therapy, plasma norepinephrine decreased significantly from a mean ± SEM of 552 ± 80 to 390 ± 37 ng/ml. In addition, the RR interval increaed significantly from 719 ± 19 to 771 ± 20 ms. High frequency power increased from 84 ± 24 to 212 ± 72ms², and the root mean square of successive differences in RR interval increased from 203 ± 1.8 to 27.0 ± 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 ± 80 to 482 ± 144 ms²) by digoxin therapy. Conclusions. These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.