The consequences of contracting early and often

Abstract

Frequent premature ventricular contractions (PVCs) are associated with structural heart disease and an increase in sudden and overall mortality. PVCs themselves, if in sufficient numbers, may be associated with the development of a reversible form of cardiomyopathy (CM). A number of small series have suggested that PVC density and features, such as QRS duration, location of origin, and coupling, may increase the predilection to cause CM in structurally normal and diseased hearts. Moreover, elimination of PVCs by catheter ablation has improved ventricular function. Thus, frequent PVCs are a previously underappreciated target for therapeutic intervention in CM. However, the fundamental triggers for the development of myopathy and the details of structural and electrical remodeling have been impeded by the development of a suitable model system. Pacing has been exploited to generate reversible forms of tachycardia-induced CM. Huizar et al have used a premature pacing algorithm to create a model of PVC-induced CM in structurally normal hearts. The algorithm generates a high PVC burden, in this case in a bigeminal pattern pacing from the right ventricular apex. PVC pacing increased the heart rate, on average, from 80 bpm to approximately 130 bpm over 4 months of pacing. Previous characterization of this model demonstrated reversible cardiac dilation and reduced ejection fraction with a compromise in repolarizing reserve evidenced by an increase in ventricular refractory periods. This occurred in the absence of inflammation, fibrosis, increased programmed cell death, or compromised oxidative phosphorylation. In a study reported in this issue of HeartRhythm, Wang et al describe heterogeneously prolonged action potential durations (APD) in myocytes isolated from the left ventricular free wall, associated with reductions in the transient outward (Ito) and inward rectifier (IK1) potassium currents without significant changes in the delayed rectifier (IKr, IKs) currents. The decrease in repolarizing reserve is associated