Hnatkova Katerina, Vicente Jose, Johannesen Lars, Garnett Christine, Strauss David G, Stockbridge Norman, Malik Marek
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food & Drug Administration, Silver Spring, MD, United States.
Front Physiol. 2019 Jul 25;10:934. doi: 10.3389/fphys.2019.00934. eCollection 2019.
Electrocardiogram (ECG) studies of drug-induced prolongation of the interval between the J point and the peak of the T wave (JTp interval) distinguished QT prolonging drugs that predominantly block the delayed potassium rectifier current from those affecting multiple cardiac repolarisation ion channel currents. Since the peak of the T wave depends on ECG lead, a "global" T peak requires to combine ECG leads into one-dimensional signal in which the T wave peak can be measured. This study aimed at finding the optimum one-dimensional representation of 12-lead ECGs for the most stable JTp measurements. Seven different one-dimensional representations were investigated including the vector magnitude of the orthogonal XYZ transformation, root mean square of all 12 ECG leads, and the vector magnitude of the 3 dominant orthogonal leads derived by singular value decomposition. All representations were applied to the median waveforms of 660,657 separate 10-s 12-lead ECGs taken from repeated day-time Holter recordings in 523 healthy subjects aged 33.5 ± 8.4 years (254 women). The JTp measurements were compared with the QT intervals and with the intervals between the J point and the median point of the area under the T wave one-dimensional representation (JT50 intervals) by means of calculating the residuals of the subject-specific curvilinear regression models relating the measured interval to the hysteresis-corrected RR interval of the underlying heart rate. The residuals of the regression models (equal to the intra-subject standard deviations of individually heart rate corrected intervals) expressed intra-subject stability of interval measurements. For both the JTp intervals and the JT50 intervals, the curvilinear regression residuals of measurements derived from the orthogonal XYZ representation were marginally but statistically significantly lower compared to the other representations. Using the XYZ representation, the residuals of the QT/RR, JTp/RR and JT50/RR regressions were 5.6 ± 1.1 ms, 7.2 ± 2.2 ms, and 4.9 ± 1.2 ms, respectively (all statistically significantly different; < 0.0001). The study concludes that the orthogonal XYZ ECG representation might be proposed for future investigations of JTp and JT50 intervals. If the ability of classifying QT prolonging drugs is further confirmed for the JT50 interval, it might be appropriate to replace the JTp interval since with JT50 it appears more stable.
关于药物诱导的J点与T波峰之间间期（JTp间期）延长的心电图（ECG）研究，区分了主要阻断延迟钾整流电流的QT延长药物和影响多种心脏复极离子通道电流的药物。由于T波峰取决于ECG导联，因此“整体”T波峰需要将ECG导联组合成一维信号，以便测量T波峰。本研究旨在找到用于最稳定JTp测量的12导联ECG的最佳一维表示形式。研究了七种不同的一维表示形式，包括正交XYZ变换的矢量大小、所有12个ECG导联的均方根，以及通过奇异值分解得出的3个主要正交导联的矢量大小。所有表示形式均应用于从523名年龄为33.5±8.4岁（254名女性）的健康受试者的重复日间动态心电图记录中获取的660657份单独的10秒12导联ECG的中位数波形。通过计算将测量间期与基础心率的滞后校正RR间期相关联的受试者特异性曲线回归模型的残差，将JTp测量值与QT间期以及J点与T波一维表示形式下面积的中位数点之间的间期（JT50间期）进行比较。回归模型的残差（等于个体心率校正间期的受试者内标准差）表示间期测量的受试者内稳定性。对于JTp间期和JT50间期，与其他表示形式相比，源自正交XYZ表示形式的测量的曲线回归残差略低但具有统计学显著性。使用XYZ表示形式时，QT/RR、JTp/RR和JT50/RR回归的残差分别为5.6±1.1毫秒、7.2±2.2毫秒和4.9±1.2毫秒（均具有统计学显著性差异；<0.0001）。该研究得出结论，对于未来JTp和JT50间期的研究，可能建议采用正交XYZ ECG表示形式。如果进一步证实JT50间期对QT延长药物的分类能力，由于JT50似乎更稳定，用其取代JTp间期可能是合适的。
