1280 Response to Letter Regarding, “PR Interval Identifies Clinical Response in Patients With Non-Left Bundle Branch Block: A Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy Sub-Study” by Kutyifa et al We thank Jackson et al for their interest in our study and suggesting that the benefit derived from cardiac resynchronization therapy with defibrillator (CRT-D) in nonleft bundle branch block (non-LBBB) patients with prolonged PR interval may be because of the presence of masked LBBB. In our study, left ventricular volume indices were simi- lar in both patient subgroups. Electroanatomical mapping, as the corre- spondents suggest, may be a useful method to identify masked LBBB; however, we did not have such data available in Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. We had a potential, biologically plausible explanation of why CRT-D may work in non-LBBB patients with a prolonged PR interval in our study. We hypothesized that patients with prolonged PR interval benefit from atrioventricular-resynchronization and concomitant biventricular pacing avoiding right ventricular apical pacing that has been shown del- eterious in several prior studies. 1,2 We do, however, agree with the cor- respondents that we cannot surely exclude the possibility of a masked LBBB. But even though, a proximal combination of LBBB and right bundle branch block would most likely compromise 1:1 conduction, a distal right bundle branch block added to an LBBB would not necessar- ily relate to PR prolongation. Considering this, there does not seem to be a compelling link between prolonged PR interval and masked LBBB. We agree that we did not demonstrate and do not know the exact mechanism of action in our cohort. Not knowing, however, does not take away the significant clinical effect of our finding that—for the first time—we were able to identify a patient subgroup within non-LBBB deriving clinical benefit from implantation of a CRT-D with 73% reduction in heart failure or death and 81% decrease in all-cause mortality, compared with an International Classification of Diseases-only. 3 It seems that this simple ECG parameter, prolonged PR interval is helpful to identify patients with non-LBBB who ben- efit from implantation of CRT-D whether it is a surrogate marker for masked LBBB, for altered transmitral filling, or for something else. Noting this limitation, we think that further research is warranted to identify the mechanism and prospectively assess the benefit of CRT-D in patients with mild heart failure, systolic dysfunction, non- LBBB, and a prolonged PR interval and evaluate whether our find- ings are applicable to other patient cohorts. Sources of Funding The Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy study was supported by a research grant from Boston Scientific, St. Paul, Minnesota, to the University of Rochester School of Medicine and Dentistry. M. Stockburger was supported by re- search grants by Biotronik, Boston Scientific, Medtronic, and Sorin Group. J.P. Daubert received honoraria, research grant, and fellowship support from Boston Scientific. F. Holmqvist was supported by travel grants from Sweden-America Foundation, Swedish Heart-Lung Foundation, Swedish Heart Association, and the Fulbright Commission. H. Klein received re- search grant and speaker honoraria from Boston Scientific. B. Olshansky is consultant speaker for Boston Scientific, Medtronic, consultant for BioControl, Daiichi Sankyo, Boehringer Ingelheim, DSMB member for Amarin, Boston Scientific, and Sanofi Aventis. V. Kutyifa, C. Schuger, B. Merkely, W. Zareba, and A.J. Moss received research grant from Boston Scientific. S. McNitt reports no conflicts. Disclosures None. Valentina Kutyifa, MD, PhD Heart Research Follow-Up Program University of Rochester Medical Center Rochester, NY Martin Stockburger, MD Experimental and Clinical Research Center Berlin, Germany James P. Daubert, MD Fredrik Holmqvist, MD, PhD Cardiology Department Duke University Durham, NC Brian Olshansky, MD Department of Medicine University of Iowa Health Care Iowa City, IA Claudio Schuger, MD Cardiology Department Henry Ford Hospital Detroit, MI Helmut Klein, MD Ilan Goldenberg, MD Andrew Brenyo, MD Scott McNitt, MS Heart Research Follow-Up Program University of Rochester Medical Center Rochester, NY Bela Merkely, MD, PhD Heart Center Semmelweis University Budapest, Hungary Wojciech Zareba, MD, PhD Arthur J. Moss, MD Heart Research Follow-Up Program University of Rochester Medical Center Rochester, NY References 1. 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PR interval identifies clinical response in patients with non-left bundle branch block: a MulticenterAutomatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy substudy. Circ Arrhythm Electrophysiol . 2014;7:645–651. (Circ Arrhythm Electrophysiol. 2014;7:1280.) © 2014 American Heart Association, Inc. Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org DOI: 10.1161/CIRCEP.114.002303 Correspondence *Drs Kutyifa and Stockburger contributed equally to this work. Downloaded from http://ahajournals.org by on June 17, 2020