LV Systolic Dysfunction Induced by Ventricular Ectopy: a Novel Model for PVC-induced Cardiomyopathy

Project: Research


  • Jose Francisco Huizar (PI)


Background. Premature ventricular complexes (PVCs) commonly coexist with cardiomyopathy (CM). Frequent PVCs have been identified as a reversible cause of CM, referred as 'PVC-induced CM'. However, the mechanism responsible for this CM remains unknown. Recently, we described a novel PVC-induced CM canine model in otherwise normal hearts.Objectives. Aim 1) Understand the role of LV dyssynchrony in the development of LV dysfunction associated with chronic exposure to frequent PVCs (PVC-induced CM). Aim 2) Evaluate the changes in electrophysiological myocardial properties associated to frequent PVCs and PVC-induced CM. Aim 3) Assess the minimal PVC burden required to induce CM.Hypothesis. We propose that: 1) abnormal LV mechanics (dyssynchrony), but not tachycardia, plays an important role in the development of PVC-induced CM; 2) similar to failing hearts, electrophysiologic remodeling is found in PVC-induced CM; and 3) a minimum PVC burden of 25% is required to develop PVC-induced CM. Methods. All animals (n=41) will undergo implant of an experimental pacemaker capable to deliver 50% PVCs or premature ectopic contractions (PACs). Thirty-three animals will be randomized to one of 3 groups: 1) PVC (n=11), 2) PAC (n=11), or 3) control (n=11) groups as part a 12-week premature ectopic protocol. Serial echocardiograms will be obtained throughout this protocol in all groups, to assess changes in LV function /dyssynchrony due to frequent PVCs and PACs. Baseline and final (12-week) hemodynamics and electrophysiologic properties will be compared between PVC, PAC and control group to assess changes associated to frequent PVCs and PACs. The remaining animals (n=8) will participate in a PVC burden protocol, in which the PVC burden will be increased every 8 weeks in a stepwise fashion, from 0%, 5%, 14%, 25%, 33% and 50%. Serial echocardiograms and Holters will be obtained after every increase in PVC burden to assess the effects on heart rate, LV function and development of PVC-induced CM by different PVC burdens.Significance. We expect to: 1) understand how LV dyssynchrony impacts the development of PVC-induced CM, 2) recognize the hemodynamic and electrophysiologic changes associated with PVC-induced CM, and 3) identify the minimum PVC burden required to induce PVC-induced CM. These will help us understand the clinical consequences of PVCs, the pathophysiology of PVC-induced CM and support further clinical studies in heart failure patients with frequent PVCs.
Award amount$308,000.00
Award date01/01/2012
Program typeScientist Development Grant
Award ID12SDG9310032
Effective start/end date01/01/201212/31/2015