Molecular phenotyping of atrial remodeling in atrial fibrillation using 18F-FDG and 18F-FAPI PET.

Atrial remodeling in atrial fibrillation (AF) involves multiple biological processes, including metabolic alterations, inflammation-related metabolic activity, and fibroblast activation, which can be assessed non-invasively with 18F-fluorodeoxyglucose (FDG) and fibroblast activation protein inhibitors (FAPI) PET, respectively. We aimed to characterize and compare the atrial uptake patterns of these two tracers in patients with AF. In this post hoc cardinality-matched analysis of two prospective PET/CT cohorts, 90 patients with AF were included (45 imaged with ¹⁸F-FDG and 45 with ¹⁸F-FAPI). Left atrial volume index (LAVI) was measured using the echocardiographic ellipsoid method. The prevalence, intensity, and spatial distribution of atrial tracer uptake were compared between tracers, and clinical correlates of abnormal uptake were assessed using univariable analyses and logistic regression. ¹⁸F-FAPI showed a higher left atrial (LA) target-to-background ratio than ¹⁸F-FDG (P = 0.007). Abnormal uptake was more frequent with ¹⁸F-FDG in the left atrial appendage (LAA; 83.3% vs. 23.1%, P < 0.001), and more frequent with ¹⁸F-FAPI in the LA anterior wall (84.6% vs. 38.9%, P = 0.002) and LA roof (69.2% vs. 33.3%, P = 0.019). These differences persisted in persistent AF (PsAF); in paroxysmal AF, only the higher LAA ¹⁸F-FDG uptake remained (P = 0.015). Abnormal right atrial ¹⁸F-FDG uptake was associated with PsAF (P = 0.010), whereas abnormal LA ¹⁸F-FAPI uptake was associated with higher LAVI (P = 0.021) and lower low-density lipoprotein cholesterol (P = 0.006). ¹⁸F-FDG and ¹⁸F-FAPI PET demonstrated spatially divergent atrial uptake patterns in AF, suggesting cohort-level complementary information on metabolically active atrial remodeling and activated fibroblast-associated remodeling. This complementarity requires within-patient validation.