Jie Xiao, Rodriguez Blanca, Pueyo Esther
Computing Laboratory, Oxford University, OX1 3QD, UK.
Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:2565-8. doi: 10.1109/IEMBS.2010.5626864.
QT prolongation is the only clinically proven, yet insufficient, electrocardiogram (ECG) biomarker for drug-induced cardiac toxicity. The goal of this study is to evaluate whether JT area, i.e., total area of the T-wave, can serve as an ECG biomarker for drug-induced cardiac toxicity using both signal processing and computational modeling approaches. An ECG dataset that contained recordings from patients under control and sotalol condition was analyzed. In order to relate sotalol-induced ECG changes to its effect on ion channel level, i.e., blockade of the rapid component of the delayed rectifier potassium channel (I(Kr)), varied degrees of I(Kr) blockade were simulated in a slab of ventricular tissue. The mean JT area increased by 36.5% following the administration of sotalol in patients. Simulations in the slab tissue showed that sotalol increased action potential duration preferentially in the midmyocardium, which led to increased transmural dispersion of repolarization and JT area. In conclusion, JT area reflects the transmural dispersion of repolarization and may be a potentially useful surrogate/supplemental ECG biomarker to assess drug safety.
QT间期延长是药物性心脏毒性唯一经临床证实但并不充分的心电图生物标志物。本研究的目的是使用信号处理和计算建模方法，评估JT面积（即T波总面积）是否可作为药物性心脏毒性的心电图生物标志物。分析了一个包含对照和索他洛尔条件下患者记录的心电图数据集。为了将索他洛尔引起的心电图变化与其对离子通道水平的影响（即延迟整流钾通道快速成分（I(Kr)）的阻断）联系起来，在心室组织切片中模拟了不同程度的I(Kr)阻断。患者服用索他洛尔后，平均JT面积增加了36.5%。组织切片模拟显示，索他洛尔优先增加心肌中层的动作电位持续时间，这导致复极跨壁离散度增加和JT面积增加。总之，JT面积反映复极跨壁离散度，可能是评估药物安全性的潜在有用替代/补充心电图生物标志物。
