title: Relation of QRS Duration to Clinical Benefit of Cardiac Resynchronization Therapy in Mild Heart Failure Patients Without Left Bundle Branch Block: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy Substudy.
abstract: BACKGROUND
  There are conflicting data regarding the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and without left bundle branch block.
  
  
  RESULTS
  We evaluated the long-term clinical outcomes of 537 non-left bundle branch block patients with mild HF enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study by QRS duration or morphology further stratified by PR interval. At 7 years of follow-up, the cumulative probability of HF hospitalization or death was 45% versus 56% among patients randomized to implantable cardioverter-defibrillator and CRT with defibrillator (CRT-D), respectively (P=0.209). Multivariable-adjusted subgroup analysis by QRS duration showed that patients from the lower quartile QRS duration group (≤ 134 ms) experienced 2.4-fold (P=0.015) increased risk for HF hospitalization or death with CRT-D versus implantable cardioverter-defibrillator only therapy, whereas the effect of CRT-D in patients from the upper quartiles group (QRS>134 ms) was neutral (hazard ratio [HR] =0.97, P=0.86; P value for interaction =0.024). In a second analysis incorporating PR interval, patients with prolonged QRS (>134 ms) and prolonged PR (>230 ms) were protected with CRT-D (HR=0.31, P=0.003), whereas the association was neutral with prolonged QRS (>134 ms) and shorter PR (≤ 230 ms;, HR=1.19, P=0.386; P value for interaction =0.002). The effect was neutral, regardless of morphology, right bundle branch block (HR=1.01, P=0.975), and intraventricular conduction delay (HR=1.31, P=0.172).
  
  
  CONCLUSIONS
  Overall, patients with mild HF but without left bundle branch block morphology did not derive clinical benefit with CRT-D during long-term follow-up. Relatively shorter QRS was associated with a significantly increased risk with CRT-D relative to implantable cardioverter-defibrillator -only.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.). yitschak.biton@heart.rochester.edu yitscb@gmail.com.
authors.forename: Yitschak
authors.initials: Y
authors.lastname: Biton
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Valentina
authors.initials: V
authors.lastname: Kutyifa
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Iwona
authors.initials: I
authors.lastname: Cygankiewicz
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Helmut
authors.initials: H
authors.lastname: Klein
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Anne Christine
authors.initials: AC
authors.lastname: Ruwald
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, Department of Medicine at the University of Rochester Medical Center, NY (Y.B., V.K., I.C., I.G., H.K., S.M., B.P., A.C.R., M.H.R., A.J.M., W.Z.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (A.C.R., M.H.R.); and Heart Institute, Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Y.B., I.G.).
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
mesh_terms: D000200:Action Potentials; D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects; D016009:Chi-Square Distribution; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000009:adverse effects / Q000295:instrumentation; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
keywords: bundle-branch block; heart failure; implanted cardioverter–defibrillator; morbidity/mortality; resynchronization