Life-threatening Arrhythmias Genotype-phenotype Correlation in the Long-qt Syndrome : Gene-specific Triggers for Genotype-phenotype Correlation in the Long-qt Syndrome Gene-specific Triggers for Life-threatening Arrhythmias
Life-threatening Arrhythmias Genotype-phenotype Correlation in the Long-qt Syndrome : Gene-specific Triggers for Genotype-phenotype Correlation in the Long-qt Syndrome Gene-specific Triggers for Life-threatening Arrhythmias
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9.4
通讯作者：
Ketty Lehmann;Philippe Schwartz;Raffaella Bloise Coumel;Clive Wattanasirichaigoon;Wilhelm Corbett;
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作者：
Ketty Lehmann;Philippe Schwartz;Raffaella Bloise Coumel;Clive Wattanasirichaigoon;Wilhelm Corbett;
先天性长QT综合征（LQTS）是由几个基因突变引起的，所有这些基因都编码心脏离子通道。对这些突变的电生理后果的逐步理解为基因型-表型相关性研究打开了不可预见的可能性。初步观察表明，与心脏事件相关的条件（“触发因素“）可能在很大程度上是基因特异性的。方法和结果：我们确定了670名已知基因型的LQTS患者（LQT 1，n = 371; LQT 2，n = 234; LQT 3，n = 65），他们有症状（晕厥、心脏骤停、猝死），并检查了3种特定触发因素（运动、情绪和无觉醒的睡眠/休息）是否因基因型而异。LQT 1患者的大部分事件（62%）发生在运动期间，只有3%发生在休息/睡眠期间。这些百分比在LQT 2和LQT 3患者中几乎相反，他们在运动期间发生事件的可能性较小（13%），而在休息/睡眠期间发生事件的可能性较大（29%和39%）。致命和非致命事件遵循相同的模式。LQT 1、LQT 2和LQT 3患者的校正QT间期无差异（分别为498、497和506 ms）。LQT 1组患者（分别为81%和4%）中，接受β受体阻滞剂治疗后无复发的患者比例高于LQT 2组（分别为59%和4%）和LQT 3组（分别为50%和17%），死亡率低于LQT 3组。结论：LQTS患者中危及生命的心律失常倾向于在特定情况下以基因特异性方式发生。这些数据使我们对特定基因突变的电生理后果与临床表现相关的机制有了新的认识，并提供了用基因特异性方法补充传统治疗的可能性。
Background—The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions (" triggers ") associated with cardiac events may in large part be gene specific. Methods and Results—We identified 670 LQTS patients of known genotype (LQT1, nϭ371; LQT2, nϭ234; LQT3, nϭ65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with -blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. Conclusions—Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches.