Porta Alberto, Girardengo Giulia, Bari Vlasta, George Alfred L, Brink Paul A, Goosen Althea, Crotti Lia, Schwartz Peter J
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy.
J Am Coll Cardiol. 2015 Feb 3;65(4):367-374. doi: 10.1016/j.jacc.2014.11.015.
A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes.
This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation.
Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes.
The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest.
The present data identified an additional factor contributing to the differential arrhythmic risk among patients with LQT1 carrying the same mutation. A healthy autonomic control confers a high risk, whereas patients with higher sympathetic control of the QT interval and reduced vagal control of heart rate are at lower risk. This differential "autonomic make-up," likely under genetic control, will allow refinement of risk stratification within families with LQTS, leading to more targeted management.
长QT综合征（LQTS）一个令人困惑的特征是，携带相同突变的家庭成员往往有不同的症状和临床结局。
本研究检验了一种假说，即通过对标准24小时动态心电图记录中RR和QT间期逐搏自发性变异性进行频谱分析评估的迷走神经和交感神经控制，可调节南非一个携带临床严重KCNQ1 A341V突变的LQT1奠基人群中46名成员的1型长QT综合征（LQT1）严重程度。
将非突变携带者（NMCs）（n = 14）与突变携带者（MCs）（n = 32）进行比较，其中22名有主要症状，10名无主要症状。我们评估了昼夜节律和β受体阻滞剂治疗对传统时域和频域RR及QT变异性指标的影响。
无症状MCs与有症状MCs及NMCs在心率的迷走神经控制较少以及QT间期的交感神经反应性调节较多方面存在显著差异，尤其是在白天，此时LQT1患者的心律失常风险最大。
目前的数据确定了一个导致携带相同突变的LQT1患者心律失常风险差异的额外因素。健康的自主神经控制会带来高风险，而QT间期交感神经控制较高且心率迷走神经控制降低的患者风险较低。这种不同的“自主神经构成”可能受基因控制，将有助于完善LQTS家族内的风险分层，从而实现更有针对性的管理。
