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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.

frontiers in physiology

Comparing Reentrant Drivers Predicted by Image-Based Computational Modeling and Mapped by Electrocardiographic Imaging in Persistent Atrial Fibrillation