Abstract：
Williams-Beuren Syndrome (WBS) is a rare genetic condition caused by a chromosomal microdeletion at 7q11.23. It is a multi-system disorder characterized by distinct facies, intellectual disability, and supravalvar aortic stenosis. Those with WBS are at increased risk of sudden death, but mechanisms underlying this remain poorly understood. We recently demonstrated autonomic abnormalities in those with WBS that are associated with increased susceptibility to arrhythmia and sudden cardiac death (SCD) risk. A recently introduced method for HRV analysis called \'heart rate fragmentation\' (HRF) correlates with adverse cardiovascular events and death in studies where HRV failed to identify high-risk subjects. Some argue that HRF quantifies non-autonomic cardiovascular modulators. We, therefore, sought to apply HRF analysis to a WBS cohort to: 1) determine if those with WBS show differences in HRF compared to healthy controls and 2) determine if HRF correlates with traditional HRV measures in those with WBS. Similar to studies of those with CAD and atherosclerosis, we found significantly higher HRF in those with WBS compared to healthy controls. In general, HRF shows minimal correlation with traditional HRV metrics, suggesting that HRF may quantify some non-autonomic modulators of sudden death risk in those with WBS. We also introduce a new metric inspired by the HRF methodology, Significant Acute Rate Drop (SARD), which may permit vagal activity detection more directly. HRF and SARD increase the ability of non-invasive HRV measures to identify those at greatest risk for sudden cardiac death both in those with WBS as well as populations more broadly.
摘要：
Williams-Beuren综合征（WBS）是一种罕见的遗传病，由7q11.23处的染色体微缺失引起。它是一种以不同相为特征的多系统无序，智力残疾,主动脉瓣上狭窄.患有WBS的人猝死的风险增加，但这背后的机制仍然知之甚少。我们最近证明了WBS患者的自主神经异常与心律失常和心源性猝死（SCD）风险增加有关。在HRV未能识别高风险受试者的研究中，最近引入的HRV分析方法称为“心率碎片”（HRF）与不良心血管事件和死亡相关。一些人认为HRF可以量化非自主性心血管调节剂。我们,因此,试图将HRF分析应用于WBS队列,以:1)确定与健康对照组相比,WBS患者的HRF是否存在差异;2)确定WBS患者的HRF是否与传统HRV指标相关.类似于CAD和动脉粥样硬化患者的研究，我们发现,与健康对照组相比,WBS患者的HRF显著升高.总的来说,HRF与传统HRV指标的相关性最小，表明HRF可以量化WBS患者猝死风险的一些非自主调节剂。我们还引入了一种受HRF方法启发的新指标，显著急性心率下降(SARD),这可以允许更直接地检测迷走神经活动。HRF和SARD增加了非侵入性HRV措施的能力，以识别WBS患者以及更广泛的人群中心脏猝死风险最高的人群。
