From Paroxysmal to Persistent Atrial Fibrillation: Progressive Fibrosis of the Left Atrial Posterior Wall

Background: The path from paroxysmal to persistent atrial fibrillation (AF) is still poorly understood, leading to suboptimal treatment outcomes. Objectives: In this study, the authors sought to investigate the level of fibrosis in different stages of AF with the use of ¹⁸F-labeled aluminum fluoride (AlF) targeting fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET)–magnetic resonance imaging (MRI). Methods: A total of 78 patients with AF and 49 health volunteers were enrolled in this study. All participants received FAPI-PET-MRI. Measurement of positive ratios and the proportion was performed in various regions of the left atrium posterior wall (LAPW), the atrial septum, anterior wall, appendage, and roof. Patients were categorized into paroxysmal (PAF), persistent (PsAF), and permanent (PmAF) AF groups based on 7-day ambulatory monitoring and history. Another cohort of 36 patients undergoing cardiac surgery, with 124 fragments of image-guided tissue, consented to biopsy during cardiac surgery for histology examinations. Results: The positive ratio for fibrosis was significantly higher in the PsAF and PmAF groups compared with the PAF and healthy volunteer groups across all atrial regions (P < 0.05). The LAPW showed the highest level of fibrosis. The AUC for the positive ratio was 0.991 to differentiate PAF from PsAF in the LA (cutoff: 0.072), and 0.983 in the LAPW (cutoff: 0.025). Between PsAF and PmAF, the AUC was 0.756 in the LA (cutoff: 0.382). Histologic analysis demonstrated an increased area of fibrotic deposition in regions with increased ¹⁸F-FAPI uptake. Conclusions: LAPW fibrosis may be an important factor in the progression from PAF to PsAF.