Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization
Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization
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DOI：
10.1161/circep.111.963983
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发表时间：
2011-12-01
影响因子：
8.4
通讯作者：
Makita, Naomasa
中科院分区：
文献类型：
--
作者：
Watanabe, Hiroshi;Nogami, Akihiko;Makita, Naomasa
背景-最近，我们和其他人报道了早期复极（J波）与特发性室颤有关。然而，它的临床和遗传学特征尚不清楚。方法和结果-这项研究包括50例（44名男性，年龄45 +/- 17岁）与特发性心室颤动与早期复极，和250名年龄和性别匹配的健康对照。所有患者均发生过心律失常事件，8例（16%）有猝死家族史。29例患者中有15例（52%）可通过程控电刺激诱导室颤。特发性室颤患者心率减慢，PR间期和QRS时限较对照组延长。我们在3例无关患者中鉴定了SCN 5A的非同义变体（导致A226 D、L 846 R和R367 H）。这些变体发生在哺乳动物中高度保守的残基处。在所有携带SCN 5A突变的患者中，His-心室间期延长。钠通道阻滞剂激发导致所有3例患者早期复极增加或发生室颤，但均未诊断为Brugada综合征。在异源表达研究中，所有的突变通道都不能产生任何电流。免疫染色显示，在A226 D通道和正常的交通运输缺陷R367 H和L 846 R channel. Conclusions，我们发现在心率和心脏传导和功能丧失的突变SCN 5A与早期复极相关的特发性室颤患者的减少。这些发现支持了钠电流减少增加室颤易感性的假设。(Circ心律失常电生理学2011;4：874-881）。
Background-Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear.Methods and Results-This study included 50 patients (44 men; age, 45 +/- 17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age-and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels.Conclusions-We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility. (Circ Arrhythm Electrophysiol. 2011;4:874-881.)