title: Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT.
abstract: OBJECTIVE
  The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality.
  
  
  METHODS
  Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up.
  
  
  RESULTS
  The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks.
  
  
  CONCLUSIONS
  In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy. Clinical trials.gov identifier: NCT00180271.
authors.affiliation: Cardiac Arrhythmia Services, Southcoast Health System, Fall River, MA, USA.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Sood
authors.forename: Anne-Christine H
authors.initials: AC
authors.lastname: Ruwald
authors.forename: Scott
authors.initials: S
authors.lastname: Solomon
authors.forename: James P
authors.initials: JP
authors.lastname: Daubert
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.forename: Christian
authors.initials: C
authors.lastname: Jons
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Clyne
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D058406:Cardiac Resynchronization Therapy / Q000401:mortality*; D017281:Cost of Illness; D017147:Defibrillators, Implantable / Q000009:adverse effects*; D004452:Echocardiography; D004554:Electric Countershock / Q000009:adverse effects* / Q000401:mortality; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006335:Heart Injuries / Q000209:etiology / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology; D013610:Tachycardia / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*
keywords: Anti-tachycardia pacing; ICD therapy; MADIT-CRT; Mortality; Shocks