Tse Gary, Liu Tong, Li Ka H C, Laxton Victoria, Chan Yin W F, Keung Wendy, Li Ronald A, Yan Bryan P
Department of Medicine and Therapeutics, Chinese University of Hong KongHong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, Chinese University of Hong KongHong Kong, Hong Kong.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University Tianjin, China.
Front Physiol. 2016 Oct 18;7:467. doi: 10.3389/fphys.2016.00467. eCollection 2016.
Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the , which encodes for the cardiac Na channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na, K, Ca, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.
Brugada综合征（BrS）是一种原发性电紊乱疾病，通过室性心动过速和颤动（VT/VF）的发生，使受影响个体易发生心源性猝死。最初，BrS与编码心脏钠通道的基因中的突变有关。迄今为止，已有19个基因的变异与这种疾病有关，其中分别有11、5、3和1个基因影响钠、钾、钙和起搏电流。BrS的诊断基于伴有或不伴有药物激发试验的穹窿型或马鞍型ST段抬高和/或T波倒置的心电图标准。基于异常去极化、异常复极化和电流负荷不匹配提出了三种假说来解释导致BrS的电生理机制。来自计算模型、临床前和临床研究的证据表明，BrS中发现的分子异常会导致兴奋波长（λ）改变，最终增加心律失常风险。临床医生在管理这种疾病时面临的一个主要挑战是难以预测哪些患者亚组会发生危及生命的VT/VF。到目前为止，已经使用了几种复极化风险标志物，但这些标志物忽略了传导异常以减慢和离散形式所起的作用。最近有人提出了基于λ概念并结合复极化和传导的指标。这些指标可能比现有标志物具有更好的预测价值。
