title: Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm?
abstract: OBJECTIVE
  This study sought to examine the hemodynamic and autonomic dose response to digoxin.
  
  
  BACKGROUND
  Previous studies have demonstrated an increase in contractility and heart rate variability with digitalis preparations. However, little is known about the dose-response to digoxin, which has a narrow therapeutic window.
  
  
  METHODS
  Nineteen patients with moderate heart failure and a left ventricular ejection fraction < 0.45 were studied hemodynamically using echocardiography and blood 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 conditions were altered with nitroprusside at each study. Autonomic function was studied by assessing heart rate variability on 24-h Holter monitoring and plasma norepinephrine levels during supine rest.
  
  
  RESULTS
  Low dose digoxin provided a significant increase in ventricular performance, but no further increase was seen with the moderate dose. Low dose digoxin reduced heart rate and increased heart rate variability. Moderate dose digoxin produced no additional increase in heart rate variability 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 increased parasympathetic activity.
  
  
  CONCLUSIONS
  We conclude that moderate dose digoxin provides no additional hemodynamic or autonomic benefit for patients with mild to moderate heart failure over low dose digoxin. Because higher doses of digoxin may predispose to arrhythmogenesis, lower dose digoxin should be considered in patients with mild to moderate heart failure.
authors.affiliation: Echocardiography and Cardiac Catheterization Laboratories, Dallas Veterans Administration Hospital, Texas 75216, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Slatton
authors.forename: W N
authors.initials: WN
authors.lastname: Irani
authors.forename: S A
authors.initials: SA
authors.lastname: Hall
authors.forename: L G
authors.initials: LG
authors.lastname: Marcoux
authors.forename: R L
authors.initials: RL
authors.lastname: Page
authors.forename: P A
authors.initials: PA
authors.lastname: Grayburn
authors.forename: E J
authors.initials: EJ
authors.lastname: Eichhorn
mesh_terms: D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004077:Digoxin / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin; D009638:Norepinephrine