Preprocedural M2-muscarinic acetylcholine receptor autoantibody levels predict left atrial low-voltage area severity in atrial fibrillation undergoing catheter ablation.

BACKGROUND

Autoantibodies against the M2-muscarinic acetylcholine receptor (anti-M2-R) have been implicated in atrial remodeling and atrial fibrillation (AF) pathogenesis. However, their relationship with atrial fibrosis severity, as assessed by low-voltage areas (LVAs), remains unclear.

METHODS

This prospective study included 164 patients (89 with paroxysmal AF [PAF], 75 with non-paroxysmal AF [NPAF]) undergoing first-time catheter ablation. Preprocedural plasma anti-M2-R levels were measured using ELISA. Left atrial LVAs were assessed via electroanatomic voltage mapping and categorized into four stages. Patients were grouped as having mild (≤ 20%) or moderate-to-extensive (>20%) LVA burden. Logistic regression and ROC curve analysis were used to evaluate predictors of LVA extent.

RESULTS

The anti-M2-R levels were significantly higher in NPAF patients than in PAF patients (282.8 ± 83.8 vs. 250.7 ± 74.2 ng/mL; p = 0.011). Patients with a moderate-to-extensive LVA size had higher anti-M2-R levels than those with mild LVA size (327.7 ± 85.1 vs. 251.4 ± 74.3 ng/mL; p < 0.001). In multivariate analysis, the anti-M2-R levels were significant predictor of moderate-to-extensive LVA size(OR per 10 ng/mL increase: 1.12; 95% CI: 1.05-1.20; p < 0.001). ROC analysis identified a cutoff value of 309.3 ng/mL for predicting extensive LVA (AUC: 0.75; sensitivity: 63%; specificity: 81%).

CONCLUSIONS

The preprocedural plasma anti-M2-R levels are independently associated with left atrial LVA severity in patients with AF and may serve as a minimally invasive biomarker for identifying patients with advanced atrial substrate, thereby guiding individualized ablation strategies.