title: Reduction of the risk of recurring heart failure events with cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).
abstract: OBJECTIVE
  The evaluation of the risk of recurring heart failure events (HFEs) was a pre-specified substudy of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).
  
  
  BACKGROUND
  There are limited data regarding the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the occurrence of recurring heart failure episodes after a first post-implantation HFE.
  
  
  METHODS
  Data with regard to recurring HFEs were prospectively collected for all 1,820 MADIT-CRT participants. The CRT-D versus defibrillator-only risk for nonfatal first- and subsequent-HFEs was assessed by Cox proportional hazards and Andersen-Gill proportional intensity regression modeling, respectively, in efficacy analyses recognizing active device-type during follow-up.
  
  
  RESULTS
  Multivariate analysis showed that CRT-D was associated with a significant reduction in the risk of a first HFE (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44 to 0.67, p < 0.001) and with a similar magnitude of reduction in the risk of HFEs subsequent to a first post-enrollment event (HR: 0.62, 95% CI: 0.45 to 0.85, p = 0.003). The benefit of CRT-D for the prevention of first and subsequent HFEs was pronounced among patients with left bundle branch block (HR: 0.38, 95% CI: 0.29 to 0.49, p < 0.001; and HR: 0.50, 95% CI: 0.33 to 0.76, p = 0.001, respectively) and nonsignificant in non-left bundle branch block patients (HR: 1.12, 95% CI: 0.77 to 1.64, p = 0.55; and HR: 0.99, 95% CI: 0.58 to 1.69, p = 0.96, respectively; p values for interaction: p < 0.001 and p = 0.06, respectively). The occurrences of first and second HFEs were associated with 7- and nearly 19-fold respective increases in the risk of subsequent mortality.
  
  
  CONCLUSIONS
  In the MADIT-CRT trial, the benefit of cardiac resynchronization therapy for the reduction in recurring HFEs was maintained after the occurrence of a first post-enrollment event. The occurrence of HFEs greatly increased the risk of death. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271).
authors.affiliation: Cardiology Division of the Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA. Ilan.Goldenberg@heart.rochester.edu
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: W Jackson
authors.initials: WJ
authors.lastname: Hall
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Beck
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Alon
authors.initials: A
authors.lastname: Barsheshet
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Slava
authors.initials: S
authors.lastname: Polonsky
authors.forename: Mary W
authors.initials: MW
authors.lastname: Brown
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
mesh_terms: D000368:Aged; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000628:therapy; D002037:Bundle-Branch Block / Q000150:complications / Q000628:therapy; D058406:Cardiac Resynchronization Therapy; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate