title: Use of the 6-min walk distance to identify variations in treatment benefits from implantable cardioverter-defibrillator and amiodarone: results from the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial).
abstract: OBJECTIVE
  The purpose of this study was to determine if 6-min walk test data assists in treatment decisions for patients with heart failure.
  
  
  BACKGROUND
  In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a pre-specified subgroup analysis showed that patients with New York Heart Association functional class III symptoms did not benefit from implantable cardioverter-defibrillator (ICD) therapy and appeared to be harmed by amiodarone, whereas New York Heart Association functional class II patients obtained significant survival benefit from ICD. We postulated that a more objective measure of functional capacity, such as 6-min walk (6MW) distance, might provide a better tool for selecting these preventive therapies.
  
  
  METHODS
  A 6MW test was performed before randomization in 2,397 patients. Median follow-up was 45.5 months. All-cause mortality was the primary endpoint, with cause-specific mortality (heart failure, arrhythmic) examined in secondary analyses.
  
  
  RESULTS
  The hazard ratios (HRs) for ICD therapy compared to placebo were estimated within tertiles of baseline 6MW distance: HR: 0.42 (95% confidence interval [CI]: 0.26 to 0.66) for 6MW distance >386 m (top tertile); HR: 0.57 (95% CI: 0.39 to 0.83) for 6MW distance 288 to 386 m (middle tertile); and HR: 1.02 (95% CI: 0.75 to 1.39) for 6MW distance <288 m (bottom tertile). The corresponding HRs for amiodarone compared to placebo were 0.68 (95% CI: 0.46 to 1.02) for the top, 0.86 (95% CI: 0.61 to 1.21) for the middle, and 1.56 (95% CI: 1.17 to 2.09) for the bottom tertile. The 6MW distance was inversely related to heart failure-related mortality but not to arrhythmic mortality. ICD therapy reduced arrhythmic mortality in the top 2 tertiles of 6MW, but had no effect on heart failure mortality.
  
  
  CONCLUSIONS
  A baseline 6MW distance <288 m identified a subgroup of SCD-HeFT patients who were harmed by amiodarone therapy and did not benefit from ICD. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609).
authors.affiliation: Department of Medicine, Division of Cardiology, University of Washington, Seattle, Washington. Electronic address: dfish@u.washington.edu.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Fishbein
authors.affiliation: Department of Statistics, Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: Department of Medicine, Division of Cardiology, Duke University, Durham, North Carolina.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mark
authors.affiliation: St Vincent Heart Center of Indiana, Indianapolis, Indiana.
authors.forename: Mary Norine
authors.initials: MN
authors.lastname: Walsh
authors.affiliation: Department of Medicine, Division of Cardiology, University of Washington, Seattle, Washington.
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Poole
authors.affiliation: Seattle Institute for Cardiac Research, Seattle, Washington.
authors.forename: Jill
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Seattle Institute for Cardiac Research, Seattle, Washington.
authors.forename: George
authors.initials: G
authors.lastname: Johnson
authors.affiliation: Department of Statistics, Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Cardiology, University of Washington, Seattle, Washington; Seattle Institute for Cardiac Research, Seattle, Washington.
authors.forename: Gust H
authors.initials: GH
authors.lastname: Bardy
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D005080:Exercise Test / Q000379:methods*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D016138:Walking / Q000502:physiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone
keywords: 6-min walk; amiodarone; congestive heart failure; implantable cardioverter-defibrillator; sudden cardiac death