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Purpose: The expression of nerve growth factor-β (NGF-β) is related to cardiac nerve sprouting and sympathetic hyper innervation. We investigated the changes of plasma levels of NGF-β and the relationship to follow-up heart rate variability (HRV) after radiofrequencycatheter ablation (RFCA) of atrial fibrillation (AF). Materials and Methods: This study included 147 patients with AF (117 men, 55.8±11.5 years, 106 paroxysmal AF) who underwent RFCA. The plasma levels of NGF-β were quantified using double sandwich enzyme linked immunosorbent assay method before (NGF-βpre) and 1 hour after RFCA (NGF-βpost-1hr). HRV at pre-procedure (HRVpre), 3 months (HRVpost-3mo), and 1 year post-procedure (HRVpost-1yr) were analyzed and compared with plasma levels of NGF-β. Results: 1) The plasma levels of NGF-β significantly increased after RFCA (20.05±11.09 pg/mL vs. 29.60±19.43 pg/mL, p<0.001). The patients who did not show increased NGF-βpost-1hr were older (p=0.023) and had greater left atrial volume index (p=0.028) than those with increased NGF-βpost-1hr. 2) In patients with NGF-βpre >18 pg/mL, low frequency components (LF)/high-frequency components(HF) (p=0.003) and the number of atrial premature contractions (APCs, p=0.045) in HRVpost-3mo were significantly higher than those with ≤18 pg/mL. 3) The LF/HF at HRVpost-3mo was linearly associated with the NGF-βpre (B=4.240, 95% CI 1.114–7.336, p=0.008) and the NGF-βpost-1hr (B=7.617, 95% CI 2.106–13.127, p=0.007). 4) Both NGF-βpre (OR=1.159, 95% CI 1.045–1.286, p=0.005) and NGF-βpost-1hr (OR=1.098, 95% CI 1.030–1.170, p=0.004) were independent predictors for the increase of LF/HF at HRVpost-3mo. Conclusion: AF catheter ablation increases plasma level of NGF-β, and high plasma levels of NGF-βpre was associated with higher sympathetic nerve activity and higher frequency of APCs in HRVpost-3mo.