Background: Chronic premature ventricular contraction-induced cardiomyopathy (PVC-CM) leads to profound electrical remodeling, yet the link between transmural repolarization gradients and non-invasive ECG manifestations is not fully established. We investigated how PVC-induced reductions in Ito and Iks currents drive transmural dispersion of repolarization (TDR) and how these changes manifest in surface ECG morphological markers.
Methods: A 50% bigeminal PVC burden was maintained in a porcine model (n=5) for 12 weeks. High-resolution optical mapping was performed using voltage-sensitive dyes (JPW-6003) across the transmural wall (endo, epi). We measured Action Potential Duration (APD) restitution and calculated the TDR. These tissue-level findings were correlated with surface ECG markers, specifically the T-peak to T-end interval (Tp-e) and T-wave triangulation.
Results: PVC-CM hearts demonstrated a pro-arrhythmic phenotype characterized by significant reduction in potassium repolarization currents (Ito and IKs). Analysis of APD restitution curves revealed a significant increase in the maximum slope within the epicardial layers compared to baseline, indicating a heightened susceptibility to repolarization alternans. These spatial variations in restitution kinetics directly paralleled observed T-wave triangulation on the surface ECG. Furthermore, the epicardium exhibited disproportionate APD prolongation relative to the endocardium, driving a marked increase in both transmural dispersion of repolarization (TDR) and Tp-e intervals. This tissue-level TDR showed a strong linear correlation with the surface ECG interval (Tp-e), validating the surrogate markers accuracy.
Conclusion: Chronic PVC burden induces a Long QT-like phenotype with increased transmural heterogeneity. The high correlation between TDR and validates the use of surface ECG morphology as a surrogate for monitoring the progression of substrate remodeling. Our findings also highlight that specialized signal processing is requisite to capture the high-frequency components of the remodeled repolarization phase.