title: PR interval identifies clinical response in patients with non-left bundle branch block: a Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy substudy.
abstract: BACKGROUND
  In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), patients with non-left bundle branch block (LBBB; including right bundle branch block, intraventricular conduction delay) did not have clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D). We hypothesized that baseline PR interval modulates clinical response to CRT-D therapy in patients with non-LBBB.
  
  
  RESULTS
  Non-LBBB patients (n=537; 30%) were divided into 2 groups based on their baseline PR interval as normal (including minimally prolonged) PR (PR <230 ms) and prolonged PR (PR ≥230 ms). The primary end point was heart failure or death. Separate secondary end points included heart failure events and all-cause mortality. Cox proportional hazards regression models were used to compare risk of end point events by CRT-D to implantable cardioverter defibrillator therapy in the PR subgroups. There were 96 patients (22%) with a prolonged PR and 438 patients (78%) with a normal PR interval. In non-LBBB patients with a prolonged PR interval, CRT-D treatment was associated with a 73% reduction in the risk of heart failure/death (hazard ratio, 0.27; 95% confidence interval, 0.13-0.57; P<0.001) and 81% decrease in the risk of all-cause mortality (hazard ratio, 0.19; 95% confidence interval, 0.13-0.57; P<0.001) compared with implantable cardioverter defibrillator therapy. In non-LBBB patients with normal PR, CRT-D therapy was associated with a trend toward an increased risk of heart failure/death (hazard ratio, 1.45; 95% confidence interval, 0.96-2.19; P=0.078; interaction P<0.001) and a more than 2-fold higher mortality (hazard ratio, 2.14; 95% confidence interval, 1.12-4.09; P=0.022; interaction P<0.001) compared with implantable cardioverter defibrillator therapy.
  
  
  CONCLUSIONS
  The data support the use of CRT-D in MADIT-CRT non-LBBB patients with a prolonged PR interval. In non-LBBB patients with a normal PR interval, implantation of a CRT-D may be deleterious.
  
  
  BACKGROUND
  http://clinicaltrials.gov; Unique Identifier: NCT00180271.
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.). Valentina.Kutyifa@heart.rochester.edu.
authors: Valentina
authors: V
authors: Kutyifa
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Martin
authors: M
authors: Stockburger
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: James P
authors: JP
authors: Daubert
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Fredrik
authors: F
authors: Holmqvist
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Brian
authors: B
authors: Olshansky
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Claudio
authors: C
authors: Schuger
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Helmut
authors: H
authors: Klein
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Ilan
authors: I
authors: Goldenberg
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Andrew
authors: A
authors: Brenyo
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Scott
authors: S
authors: McNitt
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Bela
authors: B
authors: Merkely
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Wojciech
authors: W
authors: Zareba
authors: From the University of Rochester Medical Center, NY (V.K., H.K., I.G., A.B., S.M., W.Z., A.J.M.); Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (M.S.); Cardiology Department, Duke University, Durham, NC (J.P.D., F.H.); Department of Medicine, University of Iowa Health Care (B.O.); Henry Ford Hospital, Detroit, MI (C.S.); and Semmelweis University, Heart Center, Budapest, Hungary (B.M.).
authors: Arthur J
authors: AJ
authors: Moss
mesh_terms: D000200:Action Potentials; D000368:Aged; D002037:Bundle-Branch Block / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects / Q000401:mortality; D058409:Cardiac Resynchronization Therapy Devices; D016009:Chi-Square Distribution; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
keywords: atrioventricular block; cardiac resynchronization therapy; defibrillators, implantable; heart failure; mortality