Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome.
Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome.
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DOI：
10.1161/jaha.112.000570
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发表时间：
2012-04
影响因子：
5.4
通讯作者：
Lopes CM
中科院分区：
文献类型：
--
作者：
Couderc JP;Xia X;Denjoy I;Extramiana F;Maison-Blanche P;Moss AJ;Zareba W;Lopes CM
基因型-表型研究显示，1型长QT综合征（LQT-1）患者发生心脏事件的风险显著更高，尤其是在成年女性中，KCNQ 1基因α亚基胞质环（C环）区域的错义突变与肾上腺素能刺激引起的离子通道激活受损相关。我们推测，对心率增加的反应受损导致QT-RR动态曲线异常，是这些患者心脏风险增加的原因。我们测量了携带与肾上腺素能刺激受损相关突变（C环，n=18）的LQT-1患者的24小时霍尔特ECG的QT-RR斜率，并与携带其他突变（非C环，n=48）的LQT-1患者和健康对照组（n=195）进行了比较。C环突变患者的昼夜QT RR斜率（0.10±0.05）较非C环突变患者的昼夜QT RR斜率（0.17±0.09）小（P=0.002）。对于女性患者，心率减慢与QT延长和QT-RR斜率增加相关。C环突变的男性患者表现出比女性更短心率范围的复极受损，这与该综合征事件触发因素的性别差异一致。我们的观察结果表明，C环LQT-1患者有特定的受损肾上腺素调节心室复极。这种对心率增加的反应可能有助于识别遗传性QT延长的高危患者，并可能有助于选择最佳的抗心律失常治疗策略。（J Am Heart Assoc.2012;1：e000570 doi：10.1161/JAHA.112.000570.）
Genotype-phenotype investigations have revealed significantly larger risk for cardiac events in patients with type 1 long-QT syndrome (LQT-1), particularly in adult females, with missense mutation in the cytoplasmic loop (C-loop) regions of the α subunit of the KCNQ1 gene associated with an impaired ion channel activation by adrenergic stimulus. We hypothesize that the impaired response to increases in heart rate leads to abnormal QT-RR dynamic profiles and is responsible for the increased cardiac risk for these patients. We measured the QT-RR slope in 24-hour Holter ECGs from LQT-1 patients with the mutations associated with impaired adrenergic stimulus (C-loop, n=18) and compared to LQT-1 patients with other mutations (non–C-loop, n=48), and to a healthy control group (n=195). The diurnal QT-RR slope was less steep in C-loop mutation patients (0.10±0.05) than in the ECGs from non–C-loop mutation patients (0.17±0.09, P=0.002). For female patients, slower heart rates were associated with prolonged QT and increased QT-RR slope. Male patients with C-loop mutations showed an impaired repolarization for shorter range of heart rates than in females, which is consistent with gender differences in triggers for events in this syndrome. Our observations suggest that the C-loop LQT-1 patients have specific impaired adrenergic regulation of the ventricular repolarization. This response to heart rate increases may be useful in identification of high-risk patients with inherited prolonged QT and may help select an optimal antiarrhythmic therapeutic strategy. (J Am Heart Assoc. 2012;1:e000570 doi: 10.1161/JAHA.112.000570.)