Abstract
Electrocardiographic mapping (ECGI) detects reentrant drivers (RDs) that perpetuate arrhythmia in persistent AF (PsAF). Patient-specific computational models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) identify all latent sites in the fibrotic substrate that could potentially sustain RDs, not just those manifested during mapped AF. The objective of this study was to compare RDs from simulations and ECGI (RD(sim)/RD(ECGI)) and analyze implications for ablation. We considered 12 PsAF patients who underwent RD(ECGI) ablation. For the same cohort, we simulated AF and identified RD(sim) sites in patient-specific models with geometry and fibrosis distribution from pre-ablation LGE-MRI. RD(sim)- and RD(ECGI)-harboring regions were compared, and the extent of agreement between macroscopic locations of RDs identified by simulations and ECGI was assessed. Effects of ablating RD(ECGI)/RD(sim) were analyzed. RD(sim) were predicted in 28 atrial regions (median [inter-quartile range (IQR)] = 3.0 [1.0; 3.0] per model). ECGI detected 42 RD(ECGI)-harboring regions (4.0 [2.0; 5.0] per patient). The number of regions with RD(sim) and RD(ECGI) per individual was not significantly correlated (R = 0.46, P = ns). The overall rate of regional agreement was fair (modified Cohen's κ(0) statistic = 0.11), as expected, based on the different mechanistic underpinning of RD(sim)- and RD(ECGI). nineteen regions were found to harbor both RD(sim) and RD(ECGI), suggesting that a subset of clinically observed RDs was fibrosis-mediated. The most frequent source of differences (23/32 regions) between the two modalities was the presence of RD(ECGI) perpetuated by mechanisms other than the fibrotic substrate. In 6/12 patients, there was at least one region where a latent RD was observed in simulations but was not manifested during clinical mapping. Ablation of fibrosis-mediated RD(ECGI) (i.e., targets in regions that also harbored RD(sim)) trended toward a higher rate of positive response compared to ablation of other RD(ECGI) targets (57 vs. 41%, P = ns). Our analysis suggests that RDs in human PsAF are at least partially fibrosis-mediated. Substrate-based ablation combining simulations with ECGI could improve outcomes.