title: Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT.
abstract: OBJECTIVE
  To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify the action and limitations of cardiac resynchronization therapy (CRT) in relieving myocardial dysfunction.
  
  
  RESULTS
  In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), during 4 years of follow-up, 169 (9.3%) of 1820 patients died of known causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P < 0.001; HR 1.80, P = 0.035, respectively], as was diabetes (HR 1.79, P = 0.006; HR 1.73, P = 0.038, respectively), and the worst New York Heart Association Class > II more than 3 months prior to enrolment (HR 1.90, P = 0.012; HR 2.46, P = 0.010, respectively). Baseline left atrial volume index was significantly associated only with cardiac mortality (HR 1.28 per 5 unit increase, P < 0.001). Ischaemic cardiomyopathy was associated only with non-cardiac death (HR 3.54, P = 0.001). CRT-D vs. an ICD-only was associated with a reduced risk for cardiac death in patients with left bundle branch block (LBBB) (HR 0.56, P = 0.029) but was associated with an increased risk for non-cardiac death in non-LBBB patients (HR 3.48, P = 0.048).
  
  
  CONCLUSIONS
  In MADIT-CRT, two-thirds of the deaths were cardiac and one-third non-cardiac. Many of the same risk factors were associated with both cardiac and non-cardiac mortalities. CRT-D was associated with a reduced risk for cardiac death in LBBB but an increased risk for non-cardiac death in non-LBBB.
  
  
  BACKGROUND
  Information for the MADIT-CRT main study http://www.clinicaltrials.gov, NCT00180271.
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000 (Kajaanintie 50), FIN-90014 Oulu, Finland juha.perkiomaki@oulu.fi.
authors.forename: Juha S
authors.initials: JS
authors.lastname: Perkiomaki
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA Department of Cardiology, Gentofte Hospital, Hellerup, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Ruwald
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Kutyifa
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA Department of Cardiology, Gentofte Hospital, Hellerup, Denmark.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Mcnitt
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.affiliation: Cardiology Division, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldstein
authors.affiliation: Cardiology Division, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Haigney
authors.affiliation: Division of Cardiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Krone
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D000368:Aged; D002037:Bundle-Branch Block / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects / Q000401:mortality*; D058409:Cardiac Resynchronization Therapy Devices; D009202:Cardiomyopathies / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D002423:Cause of Death; D016009:Chi-Square Distribution; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality*; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
keywords: Cardiac resynchronization therapy; Causes of death; Heart failure; Implantable cardioverter-defibrillators; Ischaemic cardiomyopathy; Non-ischaemic cardiomyopathy