Regional repolarization shortening is more arrhythmogenic than regional conduction slowing in an ex vivo porcine experimental model

Abstract

Ventricular fibrillation (VF) is a major cause of sudden cardiac death. In patients without apparent structural heart disease, J-point elevation and J waves are often associated with an increased risk to VF. The mechanisms underlying these ECG patterns and the associated arrhythmogenesis are still debated. To investigate the respective role of conduction and repolarization heterogeneities in the emergence of J-waves and in the vulnerability to VF. Epi- and endocardial optical mapping experiments were performed in porcine right ventricular (RV) wedge preparations ( n = 26). Both right coronary and left anterior descending (LAD) arteries were perfused separately with Tyrode, followed by addition of either pinacidil (PINA; 20 μM, n = 14) or flecainide (FLECA; 2 μM, n = 12) in the LAD only. RV action potentials (AP) properties were assessed at 1 to 4 Hz stimulation frequencies, and a bath ECG was recorded to evaluate ST segment changes. Spontaneous or induced arrhythmias were quantified and analyzed to calculate dominant frequencies (DF) and regularity index (RI). Local perfusion of PINA induced strong AP duration and repolarization time (RT) heterogeneity on epi- and endocardial surfaces while regional FLECA perfusion significantly prolonged total activation time and increased RT heterogeneity. Both models were associated with changes in ST segment, but those of conduction heterogeneity were more subtle. They both decreased RI of arrhythmias compared to the baseline (0.53 vs. 0.84 P = 0.02 for PINA; 0.47 vs. 0.76 P = 0.06 for FLECA), and DF were significantly higher for PINA compared to FLECA (9.41 vs. 7.74 P = 0.03). Spontaneous VFs are more frequent with a local perfusion of PINA compared to FLECA (86 vs. 8% P = 0.0001). Regional repolarization shortening and conduction slowing result in specific ECG phenotypes and distinct VF dynamics. In our porcine model, repolarization heterogeneity is associated with a higher risk to VF.