PURPOSE: The expression of nerve growth factor-beta (NGF-beta) is related to cardiac nerve sprouting and sympathetic hyper innervation. We investigated the changes of plasma levels of NGF-beta and the relationship to follow-up heart rate variability (HRV) after radiofrequency catheter 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-beta were quantified using double sandwich enzyme linked immunosorbent assay method before (NGF-betapre) and 1 hour after RFCA (NGF-betapost-1 hr). HRV at pre-procedure (HRVpre), 3 months (HRVpost-3 mo), and 1 year post-procedure (HRVpost-1 yr) were analyzed and compared with plasma levels of NGF-beta. RESULTS: 1) The plasma levels of NGF-beta 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-betapost-1 hr were older (p=0.023) and had greater left atrial volume index (p=0.028) than those with increased NGF-betapost-1 hr. 2) In patients with NGF-betapre>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-3 mo were significantly higher than those with </=18 pg/mL. 3) The LF/HF at HRVpost-3 mo was linearly associated with the NGF-betapre (B=4.240, 95% CI 1.114-7.336, p=0.008) and the NGF-betapost-1 hr (B=7.617, 95% CI 2.106-13.127, p=0.007). 4) Both NGF-betapre (OR=1.159, 95% CI 1.045-1.286, p=0.005) and NGF-betapost-1 hr (OR=1.098, 95% CI 1.030-1.170, p=0.004) were independent predictors for the increase of LF/HF at HRVpost-3 mo. CONCLUSION: AF catheter ablation increases plasma level of NGF-beta, and high plasma levels of NGF-betapre was associated with higher sympathetic nerve activity and higher frequency of APCs in HRVpost-3 mo.