Data Sheet 1_Tracking changes in autonomic function by coupled analysis of wavelet-based dispersion of heart rate variability and gastrointestinal symptom severity in individuals with hypermobile Ehlers–Danlos syndrome.docx

IntroductionPeople with hypermobile Ehlers–Danlos syndrome (hEDS) experience multisystemic dysfunction with varying severity and unpredictability of flare occurrence. Cohort studies suggest that individuals with hEDS have a higher risk for autonomic dysfunction. The gold standard for assessing autonomic function, clinically, is the heart rate variability (HRV) assessment from 24-h Holter monitor electrocardiogram data, but this is expensive and can only be performed in short durations. Since their advent, biometric devices have been a non-invasive method for tracking HRV to assess autonomic function. This study aimed to understand the intra- and inter-individual variability in autonomic function and to associate this variability with gastrointestinal symptoms in individuals with hEDS using wearable devices.
MethodsWe studied 122 days of biometric device data from 26 individuals, including 35 days highlighted as high gastrointestinal (GI) dysfunction and 48 days as low GI dysfunction. Utilizing wavelet analysis to assess the frequency domains of heart rate signals, we compared participants’ HRV data for high, low, very low (VLF), and ultralow (ULF) frequency domains associated with physiological differences.
ResultsWe found a significant difference between the VLF and ULF signals on high-GI symptom days compared with low-symptoms days for 92 and 76% of the signals sampled, respectively.
DiscussionOur pilot data show a change in HRV for individuals with hEDS experiencing a flare day for a single-body system. Future research will focus on evaluating the relationship between longitudinal multisystemic symptom severity fluctuations and HRV.

引言：过度活动型埃勒斯-当洛斯综合征（hypermobile Ehlers–Danlos syndrome, hEDS）患者会出现多系统功能障碍，其病情加重发作的严重程度与发作时机均存在差异且难以预测。队列研究表明，hEDS患者发生自主神经功能障碍的风险更高。临床中评估自主神经功能的金标准，是基于24小时动态心电图监测数据的心率变异性（heart rate variability, HRV）分析，但该方法成本高昂且仅能在短时间内开展。自生物监测设备问世以来，其已成为无创追踪心率变异性以评估自主神经功能的手段。本研究旨在借助可穿戴设备，探究hEDS患者自主神经功能的个体内与个体间变异性，并将该变异性与胃肠道症状相关联。方法：本研究纳入26名受试者共计122天的生物监测设备数据，其中35天被标记为高胃肠道（gastrointestinal, GI）功能障碍，48天为低胃肠道功能障碍。研究采用小波分析对心率信号的频域特征进行评估，对比受试者在高、低、极低频（very low frequency, VLF）以及超低频（ultralow frequency, ULF）频域的心率变异性数据，上述频域均与生理差异存在关联。结果：我们发现，与低症状天数相比，高胃肠道症状天数的极低频与超低频信号存在显著差异，分别在92%和76%的采样信号中得以体现。讨论：本预实验数据显示，当hEDS患者单一身体系统出现病情加重发作时，其心率变异性会发生改变。未来研究将聚焦于评估纵向多系统症状严重程度波动与心率变异性之间的关联。