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
Circulation: Arrhythmia and Electrophysiology
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 similar in both patient subgroups. Electroanatomical mapping, as the correspondents 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 deleterious in several prior studies.1,2 We do, however, agree with the correspondents 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 necessarily 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 benefit 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 findings are applicable to other patient cohorts.
Valentina Kutyifa, MD, PhDHeart Research Follow-Up ProgramUniversity of Rochester Medical CenterRochester, NY
Martin Stockburger, MDExperimental and Clinical Research CenterBerlin, Germany
James P. Daubert, MDFredrik Holmqvist, MD, PhDCardiology DepartmentDuke UniversityDurham, NC
Brian Olshansky, MDDepartment of MedicineUniversity of Iowa Health CareIowa City, IA
Claudio Schuger, MDCardiology DepartmentHenry Ford HospitalDetroit, MI
Helmut Klein, MDIlan Goldenberg, MDAndrew Brenyo, MDScott McNitt, MSHeart Research Follow-Up ProgramUniversity of Rochester Medical CenterRochester, NY
Bela Merkely, MD, PhDHeart CenterSemmelweis UniversityBudapest, Hungary
Wojciech Zareba, MD, PhDArthur J. Moss, MDHeart Research Follow-Up ProgramUniversity of Rochester Medical CenterRochester, NY
References
1.
Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, Ellenbogen K, Ehlert F, Freedman RA, Estes NA, Greenspon A, Goldman L; Mode Selection Trial in Sinus-Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. 2002;346:1854–1862.
2.
Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A; Dual Chamber and VVI Implantable Defibrillator Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA. 2002;288:3115–3123.
3.
Kutyifa V, Stockburger M, Daubert JP, Holmqvist F, Olshansky B, Schuger C, Klein H, Goldenberg I, Brenyo A, McNitt S, Merkely B, Zareba W, Moss AJ. PR interval identifies clinical response in patients with non-left bundle branch block: a Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy substudy. Circ Arrhythm Electrophysiol. 2014;7:645–651.
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© 2014 American Heart Association, Inc.
History
Published online: 1 December 2014
Published in print: December 2014
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None.
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 research 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 research 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.
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