Arrhythmogenic substrates in atrial fibrillation and the role of ablation lesions: a longitudinal biatrial digital twin study

AIMS: Arrhythmogenic fibrotic substrates facilitate reentrant activity in the atria, contributing to the perpetuation of atrial fibrillation (AF). Catheter ablation may disrupt existing reentrant pathways but can also create new ones. This longitudinal study aimed to assess whether post-ablation AF recurrence is associated with incomplete elimination of native arrhythmogenic substrates or emergence of new arrhythmogenic substrates created by ablation lesions, addressing important questions in current AF management: why some patients experience recurrence post-ablation while others do not, and whether ablation lesions themselves contribute to post-ablation arrhythmogenesis. METHODS AND RESULTS: Biatrial digital twins (DTs) derived from pre- and post-ablation contrast-enhanced magnetic resonance imaging were used to evaluate the arrhythmogenic propensity of the fibrotic substrate-quantified by potential reentry-sites (PRs) and a vulnerability index (VI) reflecting reentry inducibility. Pre- and post-ablation DT pairs were generated for 11 patients who experienced AF recurrence (R-DTs) and 11 who did not (N-DTs). In total, 58 pre-ablation PRs and 32 post-ablation PRs were detected, with a nearly even distribution of PRs between the left atrium (LA) and right atrium (RA) both pre- and post-ablation. Pre-ablation VI was similar between N-DTs and R-DTs; however, post-ablation VI was significantly higher in R-DTs (P = 0.015). N-DTs exhibited a marked reduction in PRs following ablation, whereas R-DTs did not (P = 0.017). Both groups had few residual PRs from pre- to post-ablation, but R-DTs had many newly emergent PRs. In R-DTs, emergent PRs in the RA were accompanied by a post-ablation increase in RA fibrotic burden. In the LA, where lesions were delivered, all post-ablation reentries anchored around ablation-induced scar (ScAReentries). ScAReentries were significantly more inducible than those occurring within fibrotic substrate and were nearly three times more prevalent in R-DTs, accounting for the elevated post-ablation VI. CONCLUSION: In DTs, emergent PRs in both atria underlie AF recurrence post-ablation, with ablation itself creating some PRs of high arrhythmogenic propensity.