title: Differing effects of cardiac resynchronization therapy on long-term mortality in patient subgroups of MADIT-CRT defined by baseline conduction and 1-year post-treatment left ventricular remodeling.
abstract: BACKGROUND
  Long-term mortality data after cardiac resynchronization therapy with implanted defibrillator (CRT-D) in minimally symptomatic patients are limited.
  
  
  OBJECTIVE
  To clarify influences on long-term mortality after CRT-D, we assessed MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) patient outcomes by baseline conduction abnormality and 1-year posttreatment remodeling.
  
  
  METHODS
  MADIT-CRT followed 1820 patients assigned to CRT-D or implanted cardioverter-defibrillator (ICD) only. Using Cox proportional hazards regression analysis, treatment effects (CRT-D vs ICD only) on mortality were evaluated in patients with left bundle branch block (LBBB) and non-LBBB. Among 1196 patients with echocardiography repeated at 1 year, effect of CRT-D on later mortality (landmark analysis) was analyzed by baseline conduction and 1-year change in left ventricular end-systolic volume (LVESV).
  
  
  RESULTS
  Overall mortality was not reduced by CRT-D (hazard ratio [HR] for CRT-D/ICD only 0.94; P = .72). Among 761 patients with LBBB and CRT-D, mortality trended lower (HR 0.71; P = .10) after adjustment for clinical covariates. The effect of CRT-D on mortality was further evaluated in patients who did (responders) and did not (hypo-responders) have reduction in LVESV by ≥ 30%. LBBB responders (n = 323) had significantly reduced mortality with CRT-D (HR 0.36; P = .027), and LBBB hypo-responders (n = 182) did not (HR 0.99). By contrast, non-LBBB responders (n = 89) trended toward more deaths with CRT-D (HR 2.11; P = .22). Non-LBBB hypo-responders (n = 118) had significantly worsened mortality (HR 3.72; P =.011).
  
  
  CONCLUSIONS
  In MADIT-CRT, late mortality with CRT-D varied markedly with baseline conduction defect and remodeling response. Patients with both LBBB and substantially reduced LVESV had improved mortality. Those with non-LBBB or with LBBB and less-reduced LVESV had unchanged or worsened mortality after CRT-D.
authors.affiliation: Cardiology Division, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814-4799, USA. robert.goldstein@usuhs.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldstein
authors.forename: Mark C
authors.initials: MC
authors.lastname: Haigney
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Krone
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D000368:Aged; D002037:Bundle-Branch Block / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D009202:Cardiomyopathies / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D020257:Ventricular Remodeling / Q000502:physiology*