Abstract Body (Do not enter title and authors here): Background:
Atrial fibrillation (AF) is the most common arrhythmia, associated with increased risks of stroke, heart failure, and mortality. Structural and autonomic remodeling contribute to its pathophysiology, with evidence suggesting that sympathetic denervation may promote a pro-arrhythmic substrate. 11C-Hydroxyephedrine (HED) PET enables noninvasive assessment of cardiac sympathetic innervation in AF.

Objective:
To evaluate cardiac sympathetic innervation using HED PET imaging in healthy controls vs. patients with persistent AF, and its relationship to catheter ablation (CA) outcomes.

Methods:
This prospective study enrolled patients with symptomatic persistent AF accepted for clinically indicated CA. Patients were recruited between 2016–2018 at a tertiary center. All underwent HED hybrid PET/CT imaging prior to CA aimed at pulmonary vein isolation. Clinical endpoint was freedom from AF recurrence >30 seconds. Patients had 14-day Holter monitoring at 3, 6, and 12 months, and as needed for symptoms. Image analysis was independently performed by two readers using HERMIA software. Regions of interest were drawn on transaxial, sagittal, and coronal views to capture the left atrial (LA) myocardium and blood pool activity. Minimum, maximum, and range (max–min) of standardized uptake value (SUV) and tissue-to-blood ratio (TBR) in the LA were recorded. Group comparisons used Mann–Whitney U and Kruskal–Wallis tests.

Results:
Thirty-six patients with AF and 7 healthy controls were included (9 females; 61±9 years old). In the AF group (mean LA size 45±8 mm), 26 remained AF-free and 10 had recurrence. Mean AF-free duration was 23±7 months (AF-free) vs. 6±2 months (AF-recur). Mean LA TBR minimum was 0.92±0.15 (controls), 0.66±0.22 (AF-free), and 0.67±0.25 (AF-recur) (p=0.017; Fig. 1). Compared to controls, TBR minimum was lower in AF-free (p=0.007), AF-recur (p=0.022), and all AF patients (p=0.005). TBR range was 1.86±0.28 (controls), 2.88±0.97 (AF-free), and 0.99±1.24 (AF-recur) (p=0.013; Fig. 2); it was elevated in AF-free (p=0.002) and all AF (p=0.003) but did not meet statistical significance for AF-recur (p=0.070).

Conclusion:
Patients with persistent AF exhibit marked sympathetic denervation (low TBR minimum) and regional heterogeneity (high TBR range) on HED PET, suggestive of autonomic imbalance and atrial vulnerability. These patterns may contribute to AF recurrence and warrant further study to assess their role in ablation outcomes.