Relationships between three-dimensional fibrosis distribution, atrial adiposity, and voltage abnormalities associated with persistent atrial fibrillation

AIMS: Persistent atrial fibrillation (PsAF) is often refractory to pulmonary vein isolation, a well-established AF treatment, owing to the fibrosis-remodelled substrates sustaining re-entries. Three-dimensional fibrosis distribution and atrial adiposity have been found to be essential contributors to PsAF arrhythmogenesis. We aimed to utilize late gadolinium enhancement (LGE)-MRI-derived personalized heart digital twins (DTs)-a recent promising tool for non-invasively assessing patient arrhythmogenesis-as well as contrast-enhanced cardiac computed tomography (CCT) images and electroanatomic maps (EAMs) to investigate relationships between fibrosis distribution, including endo-epi differences, adiposity infiltration, and electrophysiological abnormalities, and their influence on PsAF arrhythmogenic substrate. METHODS AND RESULTS: Digital twins incorporating fibrosis distribution were generated from consecutive PsAF patients' LGE-MRIs. Using rapid pacing, potential locations attracting re-entries (LRs) were identified in DTs. Cardiac computed tomographies were used to segment adipose tissue within pericardial sac and evaluate the distance from endocardial surface to closest adipose tissue (DEnCA). Bipolar and unipolar-low-voltage area fractions (LVFs) were extracted from EAMs. Volumetric-fibrosis fraction (FF) and surface-FF on endocardial and epicardial surfaces at LRs and non-LRs were analysed in relation to DEnCA and LVF. In 22 patients, adipose tissue volume correlated with BMI and CHA2DS2-VASc and, together with atrial-FF, predicted number of LRs. At LRs and non-LRs, while volumetric-FF was the sole determinant of LR classification, volumetric-FF correlated with endocardium-predominant fibrosis and bipolar LVF. Endocardium-predominant fibrosis was independently linked to DEnCA. CONCLUSION: This study highlights the complex interactions between structural features, such as three-dimensional fibrosis distribution and atrial adiposity infiltration, electrophysiological features, and PsAF arrhythmogenesis.