心率的神经控制是长QT综合征中一种心律失常风险修饰因素。

Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome.

作者信息

Schwartz Peter J, Vanoli Emilio, Crotti Lia, Spazzolini Carla, Ferrandi Chiara, Goosen Althea, Hedley Paula, Heradien Marshall, Bacchini Sara, Turco Annalisa, La Rovere Maria Teresa, Bartoli Antonella, George Alfred L, Brink Paul A

机构信息

Section of Cardiology, Department of Lung, Blood and Heart, University of Pavia, Pavia, Italy.

出版信息

J Am Coll Cardiol. 2008 Mar 4;51(9):920-9. doi: 10.1016/j.jacc.2007.09.069.

DOI:10.1016/j.jacc.2007.09.069

PMID:18308161

Abstract

OBJECTIVES

The purpose of this study was to test the hypothesis that differences in autonomic responses might modify clinical severity in long QT syndrome type 1 (LQT1) patients, those with KCNQ1 mutations and reduced I(Ks), in whom the main arrhythmia trigger is sympathetic activation.

BACKGROUND

Some long QT syndrome (LQTS) patients experience life-threatening cardiac arrhythmias, whereas others remain asymptomatic throughout life. This clinical heterogeneity is currently unexplained.

METHODS

In a South African LQT1 founder population segregating KCNQ1-A341V, we correlated major cardiac events to resting heart rate (HR) and to baroreflex sensitivity (BRS) on and off beta-adrenergic blockers (BB).

RESULTS

In 56 mutation carriers (MCs), mean HR was lower among asymptomatic patients (p < 0.05). Among MCs with a QT interval corrected for heart rate <or=500 ms, those in the lower HR tertile were less likely to have suffered prior cardiac events (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.04 to 0.79, p < 0.02). The BRS was lower among asymptomatic than symptomatic MCs (11.8 +/- 3.5 ms/mm Hg vs. 20.1 +/- 10.9 ms/mm Hg, p < 0.05). A BRS in the lower tertile was associated with a lower probability of being symptomatic (OR 0.13, 95% CI 0.02 to 0.96, p < 0.05). A similar trend was observed during BB. The MCs in the lower tertile for both HR and BRS were less frequently symptomatic than MCs with different patterns (20% vs. 76%, p < 0.05). Subjects with either ADRA2C-Del322-325 or homozygous for ADRB1-R389, 2 polymorphisms predicting enhanced adrenergic response, were more likely to have BRS values above the upper tertile (45% vs. 8%, p < 0.05).

CONCLUSIONS

Lower resting HR and "relatively low" BRS are protective factors in KCNQ1-A341V carriers. A plausible underlying mechanism is that blunted autonomic responses prevent rapid HR changes, arrhythmogenic when I(Ks) is reduced. These findings help understanding phenotypic heterogeneity in LQTS and identify a physiological risk modifier, which is probably genetically determined.

摘要

目的

本研究旨在验证以下假设，即自主神经反应的差异可能会改变1型长QT综合征（LQT1）患者（那些携带KCNQ1突变且I(Ks)降低的患者，其主要心律失常触发因素是交感神经激活）的临床严重程度。

背景

一些长QT综合征（LQTS）患者会经历危及生命的心律失常，而另一些患者终生无症状。目前尚无法解释这种临床异质性。

方法

在一个南非LQT1奠基者群体（该群体中KCNQ1 - A341V呈分离状态）中，我们将主要心脏事件与静息心率（HR）以及在使用和停用β - 肾上腺素能阻滞剂（BB）时的压力反射敏感性（BRS）进行关联分析。

结果

在56名突变携带者（MCs）中，无症状患者的平均心率较低（p < 0.05）。在心率校正后的QT间期≤500 ms的MCs中，处于较低心率三分位数的患者发生既往心脏事件的可能性较小（优势比[OR] 0.19，95%置信区间[CI] 0.04至0.79，p < 0.02）。无症状MCs的BRS低于有症状的MCs（11.8±3.5 ms/mm Hg对20.1±10.9 ms/mm Hg，p < 0.05）。处于较低三分位数的BRS与出现症状的可能性较低相关（OR 0.13，95% CI 0.02至0.96，p < 0.05）。在使用BB期间也观察到了类似趋势。HR和BRS均处于较低三分位数的MCs出现症状的频率低于具有不同模式的MCs（20%对76%，p < 0.05）。携带ADRA2C - Del³²²⁻³²⁵或ADRB1 - R³⁸⁹纯合子（这两种多态性预测肾上腺素能反应增强）的受试者更有可能具有高于三分位数上限的BRS值（45%对8%，p < 0.05）。