Association of resting amygdalar activity with persistent atrial fibrillation mediated by right atrial inflammation activity on ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography

Background: Recent studies have shown that resting amygdalar activity is associated with cardiovascular disease. Nevertheless, the underlying mechanisms that link resting amygdalar activity with persistent atrial fibrillation (PerAF) remain to be comprehensively delineated. We aimed to estimate the association between resting amygdalar activity, right atrium (RA) inflammatory activity, and PerAF.

Methods: In the retrospective cohort study, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG-PET/CT) imaging was performed in 104 patients with AF between January 1, 2018, and December 31, 2022 in the third Affiliated Hospital of Soochow University. Clinical data, electrocardiograms, echocardiographic assessments, and cardiac ¹⁸F-FDG uptake measurements were systematically gathered. Validated methodologies were employed to assess resting amygdalar activity, right atrium target:background ratio (RATBR), and bone-marrow activity (BMA). Associations between resting amygdalar activity and PerAF were assessed via a logistic regression model and mediation (path) analyses.

Results: Among the patients included, 60 (57.7%) had PerAF. Compared with patients with paroxysmal AF (ParAF), those with PerAF had higher resting amygdalar activity (1.11±0.16 vs. 1.47±0.27), BMA (1.66±0.48 vs. 2.12±0.65), and RATBR (1.55±0.36 vs. 2.31±0.73) (all P values <0.001). Resting amygdalar activity demonstrated a statistically significant correlation with BMA (r=0.38; P<0.001) and RATBR (r=0.44; P<0.001). BMA significantly mediated the associations between resting amygdalar activity and RATBR, accounting for 50.2% [95% confidence interval (CI): 35.8-76.7%] of this association. Resting amygdalar activity and RATBR emerged as the sole independent variable for PerAF (odds ratio =6.81; 95% CI: 2.34-19.75; P<0.001; odds ratio =9.01; 95% CI: 3.04-26.70; P<0.001). Mediation analysis suggested that RATBR significantly mediated the associations between resting amygdalar activity and PerAF, accounting for 33.2% (95% CI: 16.6-52.4%) of this association.

Conclusions: Resting amygdalar activity and RATBR evaluated by PET/CT were significantly associated with PerAF. The association of testing amygdalar activity with PerAF was in part mediated by RA inflammatory activity, which could be a potential therapeutic target for PerAF. Further prospective research is needed to determine the generalizability of these findings.