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PVC Dyssynchrony Predicts Cardiomyopathy
Study Questions:
What hemodynamic and molecular changes occur during paced premature ventricular contractions (PVCs) compared with a regular tachycardia (right ventricular tachy pacing), and does PVC dyssynchrony predict the development and severity of PVC-induced cardiomyopathy?
Methods:
A total of 35 swine underwent pacemaker implantation. Ten animals exposed to paced bigeminy from the right ventricular apex (RVA) for 14 weeks (RVA PVC) were compared with five animals exposed to regular pacing from the RVA at 140 bpm (RV-140) and a five-animal control group. To test the role of ectopic beat dyssynchrony, additional 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 LV ejection fraction (LVEF) was significantly lower in the RVA PVC group than in the RV-140 or control groups. LVEF declined significantly in the LV Epi PVC (65 to 40) and RVFW PVC (66 to 49) groups, with final LVEF significantly lower and ventricular fibrosis significantly higher in the LV Epi PVC group compared with all others. Protein levels of pRyR2, NCX-1, CaMKII-a, and PLN were up-regulated and levels of SERCA2a were down-regulated in the LV Epi PVC group compared with the control group. Longer ectopic beat QRS duration and greater LV dyssynchrony were significantly associated with larger declines in LV systolic function.
Conclusions:
In this animal model of paced ectopic beats, PVC-induced cardiomyopathy is distinct from a tachycardia-induced cardiomyopathy. Cardiomyopathy severity is strongly associated with severity of the hemodynamic derangement associated with the paced ectopic beats.
Perspective:
This study addresses a major gap in our understanding of the pathogenesis of PVC-induced cardiomyopathy, and it establishes the existence of a distinct phenotype from that of tachycardia-induced cardiomyopathy. The authors showed that PVC-induced cardiomyopathy exhibits more deranged cellular calcium handling than RV-tachy cardiomyopathy. Additionally, PVCs from the LV epicardial surface, which have wider QRS complexes, have more dyssynchrony and result in more severe cardiomyopathy. Predictors of PVC cardiomyopathy demonstrated by the authors in the swine model are consistent with observational studies in cohorts of PVC ablation patients, and should be confirmed in prospective human studies. The authors identified a potential therapeutic target (CaMKII-a inhibition), which may potentially be able to prevent PVC cardiomyopathy. This is an elegantly designed and well-executed study.
Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure
Keywords: Arrhythmias, Cardiac, Atrial Premature Complexes, Cardiac Complexes, Premature, Cardiomyopathies, Heart Failure, Models, Animal, Pacemaker, Artificial, Pericardium, Phenotype, Secondary Prevention, Stroke Volume, Systole, Tachycardia, Ventricular Premature Complexes
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