Author + information
- Received July 15, 2018
- Revision received August 23, 2018
- Accepted September 10, 2018
- Published online December 3, 2018.
- Tomos E. Walters, MD, PhD,
- Dolkun Rahmutula, MD, PhD,
- Judit Szilagyi, MD,
- Christina Alhede, MD, PhD,
- Richard Sievers, BS,
- Qizhi Fang, MD,
- Jeffrey Olgin, MD and
- Edward P. Gerstenfeld, MS, MD∗ (, )@ed_gerst@UCSF
- Section of Cardiac Electrophysiology, Department of Medicine, University of California-San Francisco, San Francisco, California
- ↵∗Address for correspondence:
Dr. Edward P. Gerstenfeld, Section of Cardiac Electrophysiology, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, California 94143.
Background The pathophysiology of cardiomyopathy associated with premature ventricular contractions (PVCs) remains unclear.
Objectives This study prospectively explored cardiomyopathy development in a swine model of paced ectopic beats.
Methods A total of 35 swine underwent pacemaker implantation. A group exposed to paced bigeminy from the right ventricular apex (RVA) for 14 weeks (RVA PVC) (n = 10) were compared with a group exposed to regular pacing from the RVA at 140 beats/min (RV-140) (n = 5) and a control group (n = 5). To test the role of ectopic beat dyssynchrony, further groups were exposed for 12 weeks to bigeminy from the right ventricular free wall (RVFW PVC) (n = 5), the left ventricular epicardium (LV Epi PVC) (n = 5) or the right atrium (premature atrial complex) (n = 5).
Results After 14 weeks, the mean left ventricular ejection fraction (LVEF) was significantly lower in the RVA PVC group than in the RV-140 or control groups (p < 0.05). LVEF declined significantly in the LV Epi PVC (65.2 ± 2.4% to 39.7 ± 3.0%; p < 0.01) and RVFW PVC (66.1 ± 2.6% to 48.6 ± 2.7%; p < 0.01) groups, with final LVEF significantly lower and ventricular fibrosis significantly higher in the LV Epi PVC group compared with all others (p < 0.05). Protein levels of pRyR2, NCX-1, CaMKII-α, and PLN were up-regulated and levels of SERCA2a were down-regulated in the LV Epi PVC group compared with the control group (p < 0.05). Longer ectopic beat QRS duration and greater LV dyssynchrony were significantly associated with larger declines in LV systolic function.
Conclusions In a swine model of paced ectopic beats, PVC-induced cardiomyopathy is phenotypically distinct from a tachycardia-induced cardiomyopathy. Cardiomyopathy severity is strongly associated with severity of the hemodynamic derangement associated with the paced ectopic beats, particularly the extent of LV dyssynchrony.
Pacemakers, pacing leads, and other consumables used for device implantation were provided for this study without charge by Medtronic Inc. This work was supported by a Cardiology Innovation Award (CIA) from UCSF to Dr. Gerstenfeld. Dr. Walters was supported by the Kenneth M. Rosen Fellowship from the Heart Rhythm Society. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 15, 2018.
- Revision received August 23, 2018.
- Accepted September 10, 2018.
- 2018 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.