Electrophysiological Substrate and Ablation Outcomes in Atrial Fibrillation With Hypertrophic Cardiomyopathy: A Propensity‐Matched Multicenter Study

ABSTRACT Background Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), yet the intracardiac electrophysiological substrate underlying recurrence following catheter ablation remains poorly characterized. We compared the atrial substrate and ablation outcomes between HCM‐AF patients and propensity‐score‐matched lone AF controls. Methods This multicenter retrospective study was conducted across three tertiary centers in Pakistan (2015–2023). Of 841 screened patients, 143 HCM‐AF patients were matched 1:1 with 143 lone AF controls on 14 covariates. Left atrial (LA) electroanatomic voltage mapping, intracardiac electrophysiological variables, and AF inducibility were compared. Primary endpoints were LA low‐voltage area (LVA) burden, AF inducibility, and 12‐month freedom from recurrence post‐ablation. Results HCM‐AF patients had greater LVA burden (29.7% ± 17.4% vs. 11.8% ± 9.7%, p < 0.001), wider AERP dispersion (41.3 ± 15.7 vs. 18.6 ± 9.4 ms, p < 0.001), and higher AF inducibility (81.8% vs. 58.7%, p < 0.001). Among 261 ablated patients, 12‐month freedom from recurrence was 51.7% in HCM‐AF versus 73.9% in lone AF ( p = 0.001). LVA burden (aHR 1.41 per 10% increase), HCM diagnosis (aHR 2.19), non‐paroxysmal AF (aHR 1.88), and AERP dispersion ≥ 30 ms (aHR 1.67) independently predicted recurrence. Latent class analysis identified three EP phenotype clusters with divergent outcomes: 81.7%, 61.4%, and 31.9% recurrence‐free survival ( p < 0.001). Complication rates were comparable (4.7% vs. 2.2%, p = 0.33). Conclusion HCM‐AF is associated with a more arrhythmogenic atrial substrate and inferior ablation outcomes compared with lone AF. LVA burden is the strongest predictor of recurrence. EP substrate phenotyping may enable meaningful risk stratification in this population.