Supplementary Material for: Risk factors and heart rate variability associated with left ventricular enlargement in patients with frequent premature ventricular contractions

Introduction: Premature ventricular contractions (PVCs) were now well recognized to carry the risk of inducing left ventricular (LV) enlargement and were closely related to the cardiac autonomic nervous activity quantified by heart rate variability (HRV) analysis. However, the relationship between LV enlargement and HRV in patients with frequent PVCs is still unclear. This study aimed to investigate the risk factors and HRV for LV enlargement in patients with Frequent PVCs. Methods: Patients with frequent PVCs (n=571), whose PVC burden counts > 10000/24h or PVC burden > 10%, were recruited. Patients were divided into LV enlargement group (n=161), defined as female left ventricular end-diastolic diameter (LVEDD) > 49.8 mm or male LVEDD > 54.2 mm, and LV normal group (n=410). Two groups were compared on their clinical, electrocardiographic, and HRV parameters. Logistic regression analysis was used to predict the risk factors of LV enlargement in patients with frequent PVCs. The parameters of echocardiography, Holter monitoring, and HRV were collected after ablation. Results: There were significant differences between the patients with left enlargement and with normal LV structure, in terms of sex, left ventricular ejection fraction (LVEF), level of N-terminal pro-brain natriuretic peptide (NT-proBNP), 24-h PVCs burden, with non-sustained ventricular tachycardia, multifocal PVCs, QRS duration of PVC and values of very low-frequency power of HRV parameter (all p<0.05). Multivariate analysis showed that female gender (odds ratio (OR)=2.753, p<0.001), increased NT-proBNP (OR=1.011, p=0.022), increased LVEF (OR=0.292, p<0.001), increased 24-hour PVCs burden (OR=1.594, p<0.001), increased standard deviation of all NN intervals (SDNN) (OR=1.100, p=0.003), increased the proportion of consecutive NN intervals that differ by more than 50ms (PNN50) (OR=0.844, p=0.026) were predictors for LV enlargement in patients with frequent PVCs. 84.4% (54/64) of patients with LV enlargement at baseline had normalized their LV structure after ablation. The values of SDNN, standard deviation of the averages of NN intervals in all 5-min segments, the square root of the mean of the sum of the squares of differences between adjacent NN intervals, pNN50, low-frequency power (LF), LF/high-frequency power ratio of patients were significantly decreased after ablation (all p<0.05). Conclusion: female gender, increased level of NT-proBNP, lower LVEF, higher PVC burden, the increased sympathetic parameters SDNN, and reduced parasympathetic parameters PNN50 were the independent risk factors of LV enlargement in patients with frequent PVCs. LV enlargement induced by PVCs can be reversible after PVC elimination by ablation. The activities of sympathetic and parasympathetic were reduced after ablation.

引言：目前学界已明确，室性早搏（Premature Ventricular Contractions, PVCs）可引发左心室扩大风险，且与通过心率变异性（Heart Rate Variability, HRV）分析量化的心脏自主神经活动密切相关。然而，频发室性早搏患者的左心室扩大与心率变异性之间的关联仍不明确。本研究旨在探讨频发室性早搏患者发生左心室扩大的危险因素及心率变异性相关指标。
方法：本研究纳入571例频发室性早搏患者，其早搏负荷为24小时内＞10000次或占总心搏数＞10%。根据左心室舒张末期内径（Left Ventricular End-Diastolic Diameter, LVEDD）将患者分为两组：女性LVEDD＞49.8mm或男性LVEDD＞54.2mm者纳入左心室扩大组（n=161），其余纳入左心室结构正常组（n=410）。比较两组患者的临床、心电图及心率变异性参数。采用logistic回归分析探讨频发室性早搏患者左心室扩大的危险因素。消融术后收集超声心动图、动态心电图监测及心率变异性相关参数。
结果：左心室扩大组与左心室结构正常组患者在性别、左心室射血分数（Left Ventricular Ejection Fraction, LVEF）、N末端B型利钠肽原（N-terminal pro-brain natriuretic peptide, NT-proBNP）水平、24小时室性早搏负荷、是否合并非持续性室性心动过速、是否为多源性室性早搏、室性早搏的QRS时限以及心率变异性参数中的极低频功率值等方面差异均具有统计学意义（均P＜0.05）。多因素分析显示，女性（比值比（Odds Ratio, OR）=2.753，P＜0.001）、NT-proBNP水平升高（OR=1.011，P=0.022）、LVEF升高（OR=0.292，P＜0.001）、24小时室性早搏负荷增加（OR=1.594，P＜0.001）、全部窦性心搏间期的标准差（Standard Deviation of all NN Intervals, SDNN）升高（OR=1.100，P=0.003）、相邻窦性心搏间期差值大于50ms的比例（Proportion of Consecutive NN Intervals Differing by >50ms, PNN50）升高（OR=0.844，P=0.026）是频发室性早搏患者发生左心室扩大的预测因素。基线时存在左心室扩大的患者中，有84.4%（54/64）在消融术后左心室结构恢复正常。消融术后，患者的SDNN、每5分钟窦性心搏间期平均值的标准差（Standard Deviation of the Averages of NN Intervals in All 5-Min Segments, SDANN）、相邻窦性心搏间期差值平方和均值的平方根（Square Root of the Mean of the Sum of Squares of Differences Between Adjacent NN Intervals, rMSSD）、PNN50、低频功率（Low-Frequency Power, LF）以及LF/高频功率（High-Frequency Power, HF）比值均显著降低（均P＜0.05）。
结论：女性、NT-proBNP水平升高、LVEF降低、室性早搏负荷升高、交感神经参数SDNN升高以及副交感神经参数PNN50降低是频发室性早搏患者发生左心室扩大的独立危险因素。室性早搏引发的左心室扩大在通过消融术消除室性早搏后可逆转。消融术后患者的交感与副交感神经活动均有所降低。