Eccentric hypertrophy in an animal model of mid- and long-term premature ventricular contraction–induced cardiomyopathy

Abstract

Background Tachycardia and heart rate irregularity are proposed triggers of premature ventricular contraction–induced cardiomyopathy (PVC-cardiomyopathy). Bigeminal premature atrial and ventricular contractions (PACs and PVCs) increase heart rate and result in rhythm irregularities but differ in their effects on ventricular synchrony. Comparing chronic bigeminal PACs with PVCs would provide insights into mechanisms of PVC-cardiomyopathy. Objective To compare the impact of chronic PACs and PVCs on ventricular hemodynamics, structure, and function. Methods Pacemakers were implanted in 27 canines to reproduce atrial (PACs, n = 7) or ventricular bigeminy (PVCs, n = 11) for 12 weeks, and compared to sham-operated animals (n = 9). Four additional animals were exposed to long-term bigeminal PVCs (48 weeks). Hemodynamic changes were assessed using a pressure-transducing catheter at baseline and 12 weeks. Cardiac remodeling was monitored by transthoracic echocardiography throughout the 12- and 48-week protocols in the respective groups. Results PVC group demonstrated a significant decrease in left ventricular (LV) ejection fraction and contractility (max dP/dt), impaired LV lusitropy (min dP/dt), and increase in LV dimensions and LV mass at 12 weeks without further deterioration beyond 16 weeks. Despite increased LV mass, relative wall thickness decreased, consistent with eccentric hypertrophy. No significant cardiac remodeling was noted in either sham or PAC groups at 12 weeks. Conclusion In contrast to bigeminal PACs, PVCs result in a cardiomyopathy characterized by reduced LV ejection fraction, LV dilation, and eccentric hypertrophy that plateaus between 12 and 16 weeks. The lack of remodeling in chronic PACs suggests that tachycardia and heart rate irregularity do not play a significant role on the development of PVC-cardiomyopathy.

The Burden of Ventricular Premature Complex Is Associated With Cardiovascular Mortality

“…To demonstrate the ventricular structural change induced by VPC, a study of programmed pacemaker stimulation simulating persistent VPC in the canine models can induce functional changes in the myocardium and lead to a significant reduction of the left ventricular systolic function (25). Previous animal models also showed that left ventricular dys-synchrony and eccentric hypertrophy caused by VPC are also considered to be associated with the deterioration of the left ventricular systolic function (26,27). Another swine model of VPC-induced cardiomyopathy model further demonstrated persistent changes in myocardial fibrosis and left ventricular dys-synchrony after the elimination of VPC (28).…”

Mechanisms of adaptive hypertrophic cardiac remodeling in a large animal model of premature ventricular contraction‐induced cardiomyopathy

“…PVCs are premature ectopic beats originating from the ventricles, evoking an abnormal and slow propagation of myocardial activation through the left ventricle (LV) as assessed by the width of the PVC‐QRS complex resulting in a dyssynchronous LV contraction. While the latter is believed to be a main trigger of PVC‐CM, 4,7–10 the mechanisms responsible for increased mortality are unclear. Animal models of frequent PVCs have shown that the imposition of chronic PVCs initially increases cardiac contractility by post‐extrasystolic potentiation, 11 followed by a progressive decline in LV ejection fraction (LVEF) noticeable at 4 weeks after PVC initiation 5,10–12 .…”

“…While the latter is believed to be a main trigger of PVC‐CM, 4,7–10 the mechanisms responsible for increased mortality are unclear. Animal models of frequent PVCs have shown that the imposition of chronic PVCs initially increases cardiac contractility by post‐extrasystolic potentiation, 11 followed by a progressive decline in LV ejection fraction (LVEF) noticeable at 4 weeks after PVC initiation 5,10–12 . The canine model also revealed that PVC‐CM is characterized by eccentric hypertrophy as portrayed by increased LV mass index but decreased relative wall thickness 10 .…”

Alterations of sarcoplasmic reticulum-mediated Ca2+ uptake in a model of premature ventricular contraction (PVC)-induced cardiomyopathy

“…Large animal models of chronic frequent PVCs are exceptionally suited to study molecular and pathophysiological adaptations of the heart underlying this cardiomyopathy [8][9][10]. The imposition of chronic PVCs on healthy experimental animals leads to LV structural remodeling, resulting in eccentric hypertrophy and cardiac dysfunction characterized by altered inotropy and lusitropy [11].…”