Heart rate variability (HRV) reveals information undetected by direct electrocardiogram morphology evaluation. Prior research indicated that patients with paroxysmal atrial fibrillation (PAF) had altered a short-term linear HRV after pulmonary vein isolation (PVI). However, the long-term changes in the nonlinear heart rate dynamics before and after PVI remain unclear. The objective was to investigate the long-term nonlinear HRV changes before and after PVI in PAF patients. We enrolled 42 drug-refractory symptomatic PAF patients who underwent PVI. Holter monitoring were done less than 1 year before, 1∼3, and 6∼12 months after PVI, respectively. The nonlinear HRV variables, including sample entropy (SampEn), multi-scale entropy (MSE), detrended fluctuation analysis (DFA), and Poincaré Plot analysis, were analyzed. Significant reductions in SD1, SD1/SD2, MSE 1∼5, MSE 6∼20, and SampEn occurred 6∼12 months after when compared to those before PVI, respectively. SD2, MSE slope 5, DFA slope 1 decreased 1∼3 months after PVI when compared to those before PVI, respectively, whereas increased significantly 6∼12 months after PVI when compared to those 1∼3 months after PVI, respectively. DFA slope2 increased significantly after PVI when compared to that before PVI. Detailed parameters are shown in the Table 1. As measured by DFA slope2, fractal correlation properties increased significantly following PVI. Heart rate complexity (MSE 1∼5, MSE 6∼20, and SampEn) and unpredictability of an RR time series (SD1/SD2) decreased significantly after PVI, whereas long-term RR interval (SD2) and short-term complexity (MSE slope 5) decreased in the 1∼3 months after PVI and then increased in 6∼12 months after PVI. These results indicated that the neuromodulation effects from PVI was far more prolonged and extensively than expected.Tabled 1Table 1. Serial changes in the HRV parametersPatients with PAF who underwent PVI (n = 42)< 1 year pre-PVI1∼3 months post-PVI6∼12 months post-PVISD121.16 ± 8.416.31 ± 11.08∗14.19 ± 8.63∗SD2177.58 ± 44.38134.92 ± 37∗146.46 ± 37.52∗+SD1/SD20.12 ± 0.060.12 ± 0.090.1 ± 0.06∗+DFA slope11.11 ± 0.240.8 ± 0.31∗0.94 ± 0.31∗+DFA slope21.07 ± 0.11.16 ± 0.13∗1.15 ± 0.11∗MSE 1∼55.62 ± 1.824.76 ± 1.74∗4.72 ± 1.59∗MSE 6∼2019.81 ± 5.6716.01 ± 5.6∗17.3 ± 4.75∗MSE slope50.06 ± 0.07-0.01 ± 0.09∗0.03 ± 0.07+SampEn1 ± 0.321.01 ± 0.290.9 ± 0.26∗+Data are expressed as (mean ± SD); DFA slope1: Detrended fluctuation analysis slope 1; DFA slope2: Detrended fluctuation analysis slope 2; MSE 1∼5, the summation of entropy values of scales 1 to 5; MSE 6∼20, the summation of entropy values of scales 6 to 20; MSE slope 5, the linear-fitted slope of scales 1 to 5; SD1, Poincaré plot standard deviation perpendicular the line of identity; SD2, Poincaré plot standard deviation along the line of identity; SD1/SD2, SD1-to-SD2 ratio; SampEn, sample entropy; *: p < 0.05 versus < 1 year pre-PVI; +: p < 0.05 versus 1∼3 months post-PVI Open table in a new tab