Left ventricular systolic dysfunction induced by ventricular ectopy: a novel model for premature ventricular contraction-induced cardiomyopathy.

Abstract

BACKGROUND:

Premature ventricular contractions (PVCs) commonly coexist with cardiomyopathy. Recently, PVCs have been identified as a possible cause of cardiomyopathy. We developed a PVC-induced cardiomyopathy animal model using a novel premature pacing algorithm to assess timeframe and reversibility of this cardiomyopathy and examine the associated histopathologic abnormalities.

METHODS AND RESULTS:

Thirteen mongrel dogs were implanted with a specially programmed pacemaker capable of simulating ventricular extrasystoles. Animals were randomly assigned to either 12 weeks of bigeminal PVCs (n = 7) or no PVCs (control, n = 6). Continuous 24-hour Holter monitoring corroborated ventricular bigeminy in the PVC group (PVC, 49.8% versus control, < 0.01%; P<0.0001). After 12 weeks, only the PVC group had cardiomyopathy, with a significant reduction in left ventricular ejection fraction (PVC, 39.7 ± 5.4% versus control, 60.7 ± 3.8%; P < 0.0001) and an increase in left ventricular end-systolic dimension (PVC, 33.3 ± 3.5 mm versus control, 23.7 ± 3.6 mm; P < 0.001). Ventricular effective refractory period showed a trend to prolong in the PVC group. PVC-induced cardiomyopathy was resolved within 2 to 4 weeks after discontinuation of PVCs. No inflammation, fibrosis, or changes in apoptosis and mitochondrial oxidative phosphorylation were observed with PVC-induced cardiomyopathy.

CONCLUSIONS:

This novel PVC animal model demonstrates that frequent PVCs alone can induce a reversible form of cardiomyopathy in otherwise structurally normal hearts. PVC-induced cardiomyopathy lacks gross histopathologic and mitochondrial abnormalities seen in other canine models of cardiomyopathy.

• Authors: Jose F Huizar, Karoly Kaszala, Jonathan Potfay, Anthony J Minisi, Edward J Lesnefsky, Antonio Abbate, Eleonora Mezzaroma, Qun Chen, Rakesh C Kukreja, Nicholas N Hoke, Leroy R Thacker 2nd, Kenneth A Ellenbogen, Mark A Wood
• Journal: Circulation. Arrhythmia and electrophysiology (Circ Arrhythm Electrophysiol) Vol. 4 Issue 4 Pg. 543-9 (Aug 2011) ISSN: 1941-3084 [Electronic] United States
• PMID: 21576277 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Topics

• Algorithms
• Animals
• Cardiac Pacing, Artificial (methods)
• Cardiomyopathies (etiology, pathology, physiopathology)
• Disease Models, Animal
• Dogs
• Echocardiography
• Mitochondria, Heart (physiology)
• Myocardium (pathology)
• Oxidative Phosphorylation
• Pacemaker, Artificial
• Stroke Volume (physiology)
• Systole (physiology)
• Ventricular Dysfunction, Left (etiology, physiopathology)
• Ventricular Premature Complexes (complications, physiopathology)