The risk factors of Atrial Substrate Remodeling in the Patients of Paroxysmal Atrial Fibrillation following Pulmonary Vein Isolation

BACKGROUND Atrial substrate remodeling (ASR) was emerged as a critical determinant of very late recurrence (VLR) in paroxysmal atrial fibrillation (PaAF). However, the multifaceted risk factors driving ASR progression and their interplay with clinical outcomes remain incompletely characterized. This study aimed to identify clinical, electrophysiological, and structural risk factors associated with ASR in PaAF patients experiencing VLR after catheter ablation (CA). METHODS A total of 1786 consecutive patients with PaAF who underwent catheter ablation at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2006 and July 2023 were screened. Patients with normal atrial substrate at baseline who subsequently experienced recurrent AF were enrolled and categorized into two cohorts: the ASR group (with ASR) and the NASR group (without ASR). A comparative assessment was performed to identify risk factors, encompassing the recurrent type of arrhythmia, CHA2DS2-VASc score, comorbidities, and pulmonary veins-left atrial (PVs-LA) reconnection, between two groups. RESULTS Of 1,786 screened patients, 102 met inclusion criteria (mean age: 61.0±10.0 years; 54% male), with 49 (48%) patients in the ASR group (mean age: 62.1±9.0 years; 45% male) and 53 (52%) in the NASR group (mean age: 61.0±10.0 years; 62% male). The ASR group had a higher CHA2DS2-VASc score, longer recurrence intervals, and a greater prevalence of recurrent persistent AF (PsAF). Notably, recurrent PsAF emerged as an independent risk factor for ASR (HR=2.66, 95%CI=1.05-6.73, P=0.04). Despite the presence of ASR, cardiac function remained preserved in both groups. CONCLUSIONS In PaAF patients with VLR, recurrent persistent AF is an independent risk factor for atrial substrate remodeling. These findings highlight the role of arrhythmia progression in driving structural-electrical remodeling, even in initially normal atrial substrates.