Author + information
- Received September 18, 2014
- Revision received November 12, 2014
- Accepted November 14, 2014
- Published online April 1, 2015.
- S.M. Afzal Sohaib, MBBS∗,
- Judith A. Finegold, MA∗,
- Sukhjinder S. Nijjer, MBChB∗,
- Ruhella Hossain, MBBS∗,
- Cecilia Linde, MD†,
- Wayne C. Levy, MD‡,
- Richard Sutton, MD∗,
- Prapa Kanagaratnam, PhD∗,
- Darrel P. Francis, MA∗∗ ( and )
- Zachary I. Whinnett, PhD∗
- ∗National Heart & Lung Institute, Imperial College, London, United Kingdom
- †Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
- ‡Division of Cardiology, University of Washington, Seattle, Washington
- ↵∗Reprint requests and correspondence:
Dr. Darrel P. Francis, International Centre for Circulatory Health, Imperial College London, 59-61 North Wharf Road, London W2 1LA, United Kingdom.
Objectives This study examined the time course of clinical events in cardiac resynchronization therapy (CRT) trials.
Background Recent randomized controlled trial results suggest that in heart failure with narrow QRS, biventricular pacing (CRT) may increase mortality. The authors proposed implant complications as the cause, rather than a progressive adverse physiological effect.
Methods The study identified all trials comparing CRT with no CRT, which reported Kaplan-Meier curves in groups defined by QRS: narrow, non–left bundle branch block (LBBB) broad, and LBBB broad. For each trial, the change in life span every 3 months up to 3.5 years (the longest time for which data are available) was calculated and a power law was fitted, that is, ∝ timen.
Results Four trials (MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure Trial], REVERSE [REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction], and EchoCRT [Echocardiography Guided Cardiac Resynchronization Therapy]), totaling 4,717 patients, reported curves for mortality or heart failure–related hospitalization, or for mortality. In patients with LBBB broad QRS (within MADIT-CRT), life span gain increased in proportion to time1.94. In contrast, in patients with non-LBBB broad QRS (within MADIT-CRT) and patients with narrow QRS (EchoCRT), life span was lost in proportion to time1.92 and time,1.96 respectively. Hospitalization-free survival showed similar patterns.
Conclusions The nonlinear growth of life span gained when a CRT device is implanted in patients with LBBB broad QRS is unfortunately mirrored by a similarly progressive loss in life span in narrow QRS heart failure. This suggests the culprit is a progressive physiological effect of pacing rather than implant complications. If these data are not sufficient, a randomized controlled trial of deactivating CRT in patients with narrow QRS may now be needed, with a primary endpoint of increasing survival.
Drs. Sohaib, Finegold, Francis, and Whinnett are supported by the British Heart Foundation (FS/10/038, FS/13/44/30291, FS/11/92/29122, FS/14/25/30676). Dr. Nijjer is supported by the Medical Research Council (UK) (G1100443). Dr. Linde is supported by the Swedish Heart Lung Foundation (Grants 20080498 and 20110406) and the Stockholm County Council (Grants 20090376 and 20110610); was the principal investigator of REVERSE, a CRT study sponsored by Medtronic, Inc.; has received research grants, speaker honoraria, and consulting fees from Medtronic, Inc.; has received speaker honoraria and consulting fees from St. Jude Medical, Inc.; and is on the advisory board of Cardio 3. Dr. Levy has received research grants from the National Institutes of Health, Amgen, Thoratec, ResMed, Impulse Dynamics, Medtronic, Inc., and HeartWare, Inc.; is a consultant to Novartis, HeartWare, Inc., GE Healthcare, Magellan Health, and PharmIn; and holds equity in PharmIn. The University of Washington has received licensing for the Seattle Heart Failure Model from Impulse Dynamics, Thoratec, and Epocrates. Dr. Sutton holds a research grant from and is a consultant to Medtronic, Inc.; is on the Speakers Bureaus of Medtronic, Inc. and St Jude Medical, Inc.; and is a shareholder of Boston Scientific, Inc. and the American Society for Clinical Investigation. Dr. Francis is a consultant to Medtronic, Inc. and Sorin. Dr. Whinnett acts as a consultant to St. Jude Medical, Inc. and Medtronic, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 18, 2014.
- Revision received November 12, 2014.
- Accepted November 14, 2014.
- American College of Cardiology Foundation