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.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Walters TE,Rahmutula D,Szilagyi J,Alhede C,Sievers R,Fang Q,Olgin J,Gerstenfeld EPdoi
10.1016/j.jacc.2018.09.059subject
Has Abstractpub_date
2018-12-11 00:00:00pages
2870-2882issue
23 Pt Aeissn
0735-1097issn
1558-3597pii
S0735-1097(18)38742-4journal_volume
72pub_type
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