Functional mapping identifies early arrhythmogenic substrate in recurrent atrial fibrillation

Abstract Background Pulmonary vein isolation (PVI) often fails to prevent atrial fibrillation (AF) recurrence, particularly in persistent AF, where the atrial substrate plays a critical role. Endocardial scar reflects late and irreversible remodeling. Hidden slow conduction (HSC), unmasked by short-coupled extrastimuli, may represent an early functional marker of the arrhythmogenic substrate. Objective This pilot study aimed to define the prevalence and distribution of HSC sites in recurrent AF and examine their relationship with structural remodeling markers, including low-voltage areas (LVAs), intramyocardial fat (inFAT), and left atrial wall thickness (LAWT). Methods Consecutive AF patients (41% persistent, 59% paroxysmal) underwent multidetector CT with ADAS 3D LA™ segmentation of inFAT and LAWT, merged with left atrial voltage maps created using a contact-force ablation catheter. HSC sites were identified as fragmented or double electrograms evoked by triple extrastimuli. Results A total of 960 points were analyzed, with 14.5% testing HSC+. HSC + sites clustered in the septum (34%) and anterior wall (14%). Compared with HSC– sites, they showed greater inFAT (dense: 79% vs 40%; admixture: 89% vs 67%; both p < 0.001) and lower voltage (0.80 vs 1.13 mV, p < 0.001), but no significant association with LVAs or LAWT. AF duration (p = 0.004) and AF type (p = 0.018) were independent predictors of increased fat infiltration. Conclusion HSC + sites cluster within fat-rich atrial regions, suggesting they may represent an early substrate component that promotes conduction slowing before the development of overt scar. Integrating HSC mapping with inFAT imaging may refine substrate characterization and guide targeted ablation strategies.