Ongoing atrial fibroblast activation after catheter ablation for atrial fibrillation: insights from [68Ga]Ga-FAPI-04 PET/CMR

Conventional CMR alone cannot capture the biological activity of inflammation or fibrosis, which may be essential for understanding arrhythmic substrate progression. We aimed to utilize [ 68 Ga]Ga-FAPI-04 PET/CMR imaging to explore the structural and functional remodeling characteristics in patients with atrial fibrillation (AF) who had undergone catheter ablation and reached a stable post-procedural state. The analysis focused on describing the potential relationships among atrial fibroblast activation, atrial structure and function, and epicardial adipose tissue (EAT) characteristics. During the stable post-ablation phase, 74% (23/31) AF patients exhibited increased [ 68 Ga]Ga-FAPI-04 uptake in LA, predominantly located in the posterior wall and around the pulmonary veins. Compared with controls, AF patients showed significantly higher LA FAPI burden accompanied by global impairment of atrial and ventricular mechanics. Patients with persistent AF demonstrated greater LA fibroblast activation burden, enlarged LA volume, and more severe reductions in LA ejection fraction (LAEF) and strains. Recurrence was characterized by a mechanical atrial failure phenotype with markedly increased LA surface volume. LA FAPI burden correlated positively with percent of late gadolinium enhancement and atrial and ventricular volumes, and inversely with LAEF and atrial and ventricular strain parameters, indicating a close association between persistent fibroblast activation and atrioventricular mechanical decompensation. In addition, EAT FAPI activity showed concordant associations with LA structural and functional remodeling, and LA FAPI burden was positively related to stroke risk scores. [ 68 Ga]Ga-FAPI-04 PET/CMR provides unique molecular insights into atrial fibroblast activation in post-ablation AF patients. The integration of molecular and functional imaging provides complementary insights that may help generate hypotheses for future individualized management.