Molecular biology and cellular mechanisms of Brugada and long QT syndromes in infants and young children
Molecular biology and cellular mechanisms of Brugada and long QT syndromes in infants and young children
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DOI：
10.1054/jelc.2001.28865
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发表时间：
2001-01-01
影响因子：
1.3
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Antzelevitch, C
心源性猝死占 1 至 13 岁儿童猝死的 19%，占 14 至 2-1 岁儿童猝死的 30%。心源性猝死的发生率有两个高峰：一个是在 45 至 75 岁之间，由冠状动脉疾病引起；另一个是在出生至 6 个月大之间，由婴儿猝死综合征引起。长期以来，心律失常在婴儿猝死综合征中的作用一直是一个争论的问题，而心律失常在一般儿童中的作用尚不明确。最近的研究结果表明，心脏的原发性电疾病，包括 Brugada 和长期心律失常，是造成心脏猝死的原因之一。导致婴儿和儿童猝死的 QT 综合征。SCN5A、HERG 和 KvLQT1 突变已被证明与危及婴儿生命的心律失常和长 QT 间期有关。这些突变会导致钠电流和钾电流发生变化，从而放大心脏内的固有电异质性，从而为折返性心律失常（包括尖端扭转型室性心动过速）的发生提供基础和触发因素。 (TdP)，通常与长 QT 综合征 (LQTS) 相关，SCN5A 突变也被证明会导致钠通道过早关闭，从而为 Brugada 综合征患者发生快速多形性室性心动过速/心室颤动奠定基础。缺口 T 波和大的复极跨壁离散度，为 TdP 的发展提供了基础。早期后除极引起的触发性搏动被认为是导致 Brugada 综合征中 TdP 的早搏，SCN5A 突变降低了钠电流密度，导致心外膜动作电位过早复极，因为在第 1 相结束时出现全部复极或无复极。心外膜动作电位穹顶的丧失，但并非如此。心内膜，在心室壁上产生复极分散，导致跨壁电压梯度，在心电图 (ECG) 中表现为 ST 段抬高，并形成一个脆弱窗口，在此期间诱导折返。在这些情况下，某些心外膜部位的动作电位穹顶丧失，但其他部位则不会，导致第 2 相折返，这提供了所有能够诱发室性心动过速/心室的期外收缩。识别患有 Brugada 和 LQTS 综合征的婴儿和儿童的实际重要性在于，大多数由于这些先天性缺陷而导致的死亡通常足以进行诊断，从而防止发生危及生命的心律失常事件，然而，对新生儿和儿童进行大规模心电图筛查一直是争论的焦点问题，包括处理假阳性的情绪影响和社会经济影响。尽管存在这些问题，但我们仍需继续质疑当前筛查方法的经济效率低下是否会取代年轻生命的价值。
Sudden cardiac death accounts for 19% of sudden deaths in children between I and 13 years of age and 30% of sudden deaths that occur between 14 anti 2 1 years of age. The incidence of sudden cardiac death displays 2 peaks: one between 45 and 75 years of age, as a result of coronary artery disease, and (lie other between birth and 6 months of age, caused by sudden infant death syndrome. The role of cardiac arrhythmias in sudden infant death syndrome has long been a matter of debate and the role of cardiac arrhythmias, in children in general is not well defined. Recent findings point to a contribution of primary electrical diseases of the heart including the Brugada and long QT syndromes to Sudden death in infants and children. Mutations in SCN5A and HERG and KvLQT1 have been shown to be associated with life-threatening arrhythmias and long QT intervals in young infants. These mutations cause changes in Sodium and potassium currents that amplify intrinsic electrical heterogeneities within the heart, thus providing a substrate as well as a trigger for the development of reentrant arrhythmias, including Torsade de Pointes (TdP), commonly associated with the long QT syndrome (LQTS). Mutations in SCN5A have also been shown to cause the sodium channel to turn off prematurely and thus to set the stage for the development of a rapid polymorphic ventricular tachycardia/ventricular fibrillation in patients with the Brugada Syndrome. In LQTS, ion channel mutations cause a preferential prolongation of the M cell action potential that contributes to the development of long QT intervals, wide-based or notched T waves, and a large transmural dispersion of repolarization, which provides the substrate for the development of TdP. An early afterdepolarization-induced triggered beat is thought to provide the extrasystole that precipitates TdP. in the Brugada syndrome, mutations in SCN5A reduce sodium current density, causing premature repolarization of the epicardial action potential due to an all or none repolarization at the end of phase 1. The loss of the action potential dome in epicardium, but not endocardium, creates a dispersion of repolarization across the ventricular wall, resulting in a transmural voltage gradient that manifests in the electrocardiogram (ECG) as an ST-segment elevation and in the development of a vulnerable window during Which reentry Call be induced. Under these conditions, loss of the action potential dome at some epicardial sites but not Others gives rise to phase 2 reentry, which provides all extrasystole capable of precipitating ventricular tachycardia/ventricular fibrillation (or rapid TdP). The practical importance of identifying infants and children with Brugada and LQTS syndromes lies in the fact that most deaths due to these congenital defects can be presented. A simple ECG is often sufficient to permit diagnosis and thus to prevent the development of life-threatening arrhythmic events. Mass ECG screening of neonates and children however has been the subject of debate focused oil issues ranging from the emotional impact of dealing with false positives to those concerning socio-economic and medico-legal factors. These issues are discussed in other articles. These concerns notwithstanding, it is important that we continue to question whether the economic inefficiencies Of Current screening methodologies Supersede the value of a young life.