Repolarization Heterogeneity in Human Post-Infarct Ventricular Tachycardia

Slow conduction, caused by fibrosis between surviving myocytes and connexin remodeling, is an important prerequisite for post-infarction ventricular tachycardia (VT); however, slow conduction is present throughout the infarct whereas VT circuits are finite in number and discrete. In a porcine model of VT, re-entrant circuits occur at region of significant repolarization heterogeneity caused by up-regulation of potassium channel β-subunits KCNE3 (increasing repolarization current) and KCNE4 (decreasing repolarization current), causing heterogeneous action potential durations.

This study was designed to determine whether re-entrant circuits in human post-infarction VT are associated with repolarization heterogeneity.

In 6 patients, left ventricular mapping was performed during induced VT to identify sites within the VT circuit. Subsequently, unipolar mapping (3.5-mm tip ablation catheter) was performed to characterize activation-recovery intervals (ARIs), which are surrogates for local action potential durations, at sites documented within the VT circuit isthmus (IN) compared to sites within the infarct scar but outside of the VT circuit (OUT).

ARIs were significantly shorter in the IN compared with the OUT sites (420.2 ± 79.3 ms vs 462 ± 52.8 ms; P = 0.01). In all patients. sites that were associated with the circuit always had shorter ARI values than did those sampled from OUT regions.

VT circuit sites in human post-infarct VT are associated with repolarization heterogeneity, similar to what was previously reported in a porcine model. This suggests the possibility of a common mechanism between humans and the porcine model of post-infarct VT, and that development of ablation strategies or small molecule or genetic therapies to restore normal repolarization kinetics may be antiarrhythmic.