Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome - Multicenter study in Japan
Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome - Multicenter study in Japan
复制标题
DOI：
10.1016/j.jacc.2004.03.043
复制
发表时间：
2004-07-07
影响因子：
24
通讯作者：
Kamakura, S
中科院分区：
文献类型：
--
作者：
Shimizu, W;Horie, M;Kamakura, S
目的：我们试图比较LQT1型先天性长QT综合征（LQTS）中位于跨膜区和KCNQ1通道c端区域突变的心律失常风险和对交感刺激的敏感性。背景：LQT1综合征常表现为表达变化和外显性不全，对交感神经刺激比其他形式更为敏感。方法从日本5个研究所招募66例共19个跨膜突变的LQT1患者（27个家族）和29例共8个c端突变的LQT1患者（10个家族）。结果：根据心电图（ECG）诊断标准，跨膜突变的患者更频繁受到影响（82%对24%，p < 0.0001），并且与lqts相关的心脏事件（所有心脏事件：55%对21%，p = 0.002；晕厥：55%对21%，p = 0.002；流产的心脏骤停或意外的心源性猝死：15%对0%，p = 0.03）比c端突变的患者更频繁。跨膜突变患者在较早年龄发生首次心脏事件的风险更高，风险比为3.4 (p = 0.006)，校正后Q-Tend每增加10ms，风险增加8%。跨膜突变患者的基线心电图参数，包括Q-Tend、Q-Tpeak和Tpeak-end间隔，显著高于c -末端突变患者（p < 0.005）。此外，跨膜突变患者的校正Q-Tend和Tpeak-end随运动的增加更为显著（p < 0.005）。结论：在这个多中心的日本人群中，与c端突变的患者相比，跨膜突变的LQT1患者先天性lqts相关心脏事件的风险更高，并且对交感刺激更敏感。(C) 2004年由美国心脏病学会基金会发布。
OBJECTIVES We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS).BACKGROUND The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms.METHODS Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes.RESULTS Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p < 0.005).CONCLUSIONS In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations. (C) 2004 by the American College of Cardiology Foundation.