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

J Am Coll Cardiol. 1995 Feb;25(2):289-94. doi: 10.1016/0735-1097(94)00417-o.


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 increased significantly from 719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212 +/- 72 ms2, and the root mean square of successive differences in RR interval increased from 20.3 +/- 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 483 +/- 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiopathology
  • Digoxin / therapeutic use*
  • Electrocardiography, Ambulatory
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / physiopathology
  • Signal Processing, Computer-Assisted
  • Time Factors


  • Digoxin
  • Norepinephrine