Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated With Premature Ventricular Contractions

Tomos E Walters; Dolkun Rahmutula; Judit Szilagyi; Christina Alhede; Richard Sievers; Qizhi Fang; Jeffrey Olgin; Edward P Gerstenfeld

doi:10.1016/j.jacc.2018.09.059

Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated With Premature Ventricular Contractions

J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2870-2882. doi: 10.1016/j.jacc.2018.09.059.

Authors

Tomos E Walters¹, Dolkun Rahmutula¹, Judit Szilagyi¹, Christina Alhede¹, Richard Sievers¹, Qizhi Fang¹, Jeffrey Olgin¹, Edward P Gerstenfeld²

Affiliations

¹ Section of Cardiac Electrophysiology, Department of Medicine, University of California-San Francisco, San Francisco, California.
² Section of Cardiac Electrophysiology, Department of Medicine, University of California-San Francisco, San Francisco, California. Electronic address: Edward.Gerstenfeld@ucsf.edu.

PMID: 30522650
DOI: 10.1016/j.jacc.2018.09.059

Abstract

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.

Keywords: cardiomyopathy; premature ventricular contraction; swine model.

MeSH terms

Animals
Cardiomyopathies / diagnosis*
Cardiomyopathies / physiopathology*
Predictive Value of Tests
Swine
Swine, Miniature
Ventricular Dysfunction, Left / diagnosis*
Ventricular Dysfunction, Left / physiopathology*
Ventricular Premature Complexes / diagnosis*
Ventricular Premature Complexes / physiopathology*