title: An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure.
abstract: OBJECTIVE
  Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data.
  
  
  RESULTS
  An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value.
  
  
  CONCLUSIONS
  QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response.
  NCT00170300, NCT00271154, NCT00251251.
authors.affiliation: National Heart and Lung Institute, Imperial College London (Royal Brompton & Harefield Hospitals) and Department of Cardiology, Castle Hill Hospital, University of Hull, Kingston-upon-Hull, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Cleland
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gold
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Claude Daubert
authors.forename: Lou
authors.initials: L
authors.lastname: Sherfesee
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.forename: Anthony S L
authors.initials: AS
authors.lastname: Tang
mesh_terms: D000368:Aged; D002037:Bundle-Branch Block / Q000503:physiopathology / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D002423:Cause of Death; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy
keywords: Cardiac resynchronization therapy; Heart failure; Morbidity; Mortality
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