Vijayakumar Ramya, Silva Jennifer N A, Desouza Kavit A, Abraham Robert L, Strom Maria, Sacher Frederic, Van Hare George F, Haïssaguerre Michel, Roden Dan M, Rudy Yoram
Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, Saint Louis, MO.
Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO.
Circulation. 2014 Nov 25;130(22):1936-1943. doi: 10.1161/CIRCULATIONAHA.114.011359. Epub 2014 Oct 7.
Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis.
Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation-recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation-recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05).
LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.
先天性长QT综合征（LQTS）是一种致心律失常性疾病，可导致晕厥和猝死。尽管其遗传基础已得到充分了解，但突变在原位人体心脏中转化为心律失常易感性的机制尚未完全明确。我们使用无创心电图成像来绘制心脏电生理基质，并检查LQTS患者是否存在复极区域异质性，而复极区域异质性是促进心律失常发生的基质。
25名基因型和表型均为阳性的LQTS受试者（9例LQT1、9例LQT2、5例LQT3和2例LQT5）接受了心电图成像检查。7名正常受试者作为对照。构建了心外膜激活图、恢复时间图、激活-恢复间期图和复极离散度图。所有患者的激活均正常。然而，与对照组相比，恢复时间和激活-恢复间期延长，表明复极延迟和动作电位时程异常延长（对照组为235±21毫秒，患者组为312±30毫秒）。激活-恢复间期延长在空间上是异质性的，复极梯度比对照组陡峭得多（119±19毫秒/厘米对2.0±2.0毫秒/厘米）。LQTS各类型之间以及各类型内部的复极梯度陡度和分布存在差异。有症状患者的复极梯度更陡峭（12例有症状患者为130±27毫秒/厘米，13例无症状患者为98±19毫秒/厘米；P<0.05）。
LQTS患者存在由局部动作电位时程延长导致的复极离散度陡峭区域。这确定了一种折返性心律失常的基质，表面心电图无法检测到。有症状患者中更陡峭的离散度表明心电图成像在风险分层中可能发挥作用。
