The mechanisms of enhanced vulnerability to atrial fibrillation caused by atrial tachycardia-induced electrical remodeling: Insights from combined activation and refractoriness mapping

Abstract

Rapid atrial activation causes electrical remodeling that promotes the occurrence of atrial fibrillation (AF). Although remodeling has been shown to alter electrophysiological variables, the spatial uniformity of these changes and their role in the enhanced vulnerability to AF are unknown. Dogs subjected to rapid atrial pacing (RAP, 400/min) for 24 hours (n = 12) were compared with sham dogs (instrumented but not paced, n = 12). Epicardial mapping (240 bipolar electrodes) and extrastimulation at a large number of sites (mean ± SEM, 66 ± 4/dog) were used to evaluate atrial activation and the heterogeneity of ERP (HERP, measured as the coefficient of variation in ERP). RAP increased the percentage of sites at which AF could be induced by single premature stimuli (from 2% ± 0.9% to 11.8% ± 2.8%, P = .007), decreased atrial ERP by 15% ( P = .003), but increased conduction velocity by 19% ( P = .0004) and thus did not alter wavelength. RAP increased the HERP (from 14.9% ± 0.9% to 20.7% ± 0.9%, P < .0001), the increase in HERP being due both to regional differences in the extent of ERP remodeling and to increased intersite variability within regions. Multilinear regression indicated that HERP was the only independent determinant of AF inducibility (r = 0.87, P = .0002). ERP per se, conduction velocity, and wavelength did not contribute to determining AF vulnerability. Combined mapping of AF induction and atrial ERP showed that in all cases premature extrastimuli induced AF at sites with short ERP by causing local conduction slowing and/or block in adjacent zones with longer ERP, thus initiating reentry and then AF. Refractoriness gradients caused by spatially remodeling create a substrate for local reentry that determines AF vulnerability in tachycardia-remodeled atria.