B-AB01-01 LOCAL REPOLARIZATION HETEROGENEITY IS MORE ARRHYTHMOGENIC THAN STRUCTURAL AND FUNCTIONAL CONDUCTION HETEROGENEITIES IN AN EX VIVO PORCINE MODEL

Abstract

VF is a major cause of sudden cardiac death. In patients without apparent structural heart disease, 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 repolarization and conduction heterogeneities in J wave’s emergence and in vulnerability to VF. Three porcine right ventricular models of either local (i) repolarization shortening, (ii) conduction slowing, or (iii) structural heterogeneity were created during ex vivo optical mapping experiments by locally perfusing (i) pinacidil (20μM, N=11) or (ii) flecainide (2μM, N=11) via a catheter introduced epicardially into a branch of the right coronary artery, or (iii) by local epicardial tissue destruction through radiofrequency application with a microneedle (9 close lesions at 30W, 1s, N=5). In each model, action potential properties and ECG were assessed. Arrhythmias were mapped and quantified. Bipolar electrograms (EGM) recordings were performed with an HD grid mapping catheter (N=3 in each group). EGM were not impacted in the first model but became locally fragmented in both conduction and structural heterogeneity areas (increased width and peaks number). We observed an increased arrhythmogenicity only in the two first models which presented 82 and 45% more spontaneous arrhythmias (p=0.0001 and 0.01 vs baseline; for (iii) 20% p=0.3), and a reduced pacing frequency threshold to induce arrhythmias (69 and 50 %, p=0.001 and 0.01 respectively vs baseline; for (iii) 25% p=0.1). During arrhythmias, repolarization heterogeneity increased focal activity and rotor number (832 vs 1410 p=0.02; 174 vs 324 p=0.04), while conduction heterogeneity did not affect dynamics and the structural one tended to reduce rotor number (235 vs 149 p=0.06) which tended to last longer. Contrary to structural and functional conduction heterogeneities, repolarization heterogeneity does not lead to EGM fragmentation in our model, but it is nevertheless associated with the highest prevalence of spontaneous VF. In terms of substrate, local repolarization shortening and structural heterogeneities had opposite effects on arrhythmia dynamics.