Focal impulse and rotor mapping (FIRM) involves intracardiac detection and catheter ablation of re-entrant drivers (RDs), some of which may contribute to arrhythmia perpetuation in persistent atrial fibrillation (PsAF). Patient-specific computational models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) has the potential to non-invasively identify all areas of the fibrotic substrate where RDs could potentially be sustained, including locations where RDs may not manifest during mapped AF episodes. The objective of this study was to carry out multi-modal assessment of the arrhythmogenic propensity of the fibrotic substrate in PsAF patients by comparing locations of RD-harboring regions found in simulations and detected by FIRM (RD_sim and RD_FIRM) and analyze implications for ablation strategies predicated on targeting RDs. For 11 PsAF patients who underwent pre-procedure LGE-MRI and FIRM-guided ablation, we retrospectively simulated AF in individualized atrial models, with geometry and fibrosis distribution reconstructed from pre-ablation LGE-MRI scans, and identified RD_sim sites. Regions harboring RD_sim and RD_FIRM were compared. RD_sim were found in 38 atrial regions (median [inter-quartile range (IQR)] = 4 [3; 4] per model). RD_FIRM were identified and subsequently ablated in 24 atrial regions (2 [1; 3] per patient), which was significantly fewer than the number of RD_sim-harboring regions in corresponding models (p < 0.05). Computational modeling predicted RD_sim in 20 of 24 (83%) atrial regions identified as RD_FIRM-harboring during clinical mapping. In a large number of cases, we uncovered RD_sim-harboring regions in which RD_FIRM were never observed (18/22 regions that differed between the two modalities; 82%); we termed such cases "latent" RD_sim sites. During follow-up (230 [180; 326] days), AF recurrence occurred in 7/11 (64%) individuals. Interestingly, latent RD_sim sites were observed in all seven computational models corresponding to patients who experienced recurrent AF (2 [2; 2] per patient); in contrast, latent RD_sim sites were only discovered in two of four patients who were free from AF during follow-up (0.5 [0; 1.5] per patient; p < 0.05 vs. patients with AF recurrence). We conclude that substrate-based ablation based on computational modeling could improve outcomes.

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