Session P94.3

Identify ECG Parameters Reflecting Repolarization Heterogeneity with a Cell-to-ECG Model

JQ Xue, WH Gao, Y Chen, XD Han*

GE Healthcare
Wauwatosa, WI, USA

Background: It has been shown that increase of heart repolarization heterogeneity is one of the key factors causing drug-induced Torsades-de-Points (TdP), together with the action potential duration (APD) prolongation, and Early Afterdepolarization (EAD) as a trigger. Before any new ECG parameters can be used side-by-side or independently in drug clinical trials, we first need to understand more clearly how sensitive those new parameters are to the heterogeneity changes, and their link with specific type of heterogeneity. The new morphology parameters also need to be robust, meaning good reproducibility.
Method: The aim of this study is to use a Cell-to-ECG model to study ECG morphology changes with three different type of heterogeneity changes: Transmural (Endo to Epicardium layers), Longitudinal (Apex to Base), Interventricular (Left to right). The heterogeneity is simulated by increasing Ikr block factors on different layers of myocardium. The model simulated ECGs were processed and measured. The ECG parameters studied include QT interval dispersion (QTeD) of standard 12-lead, QT peak dispersion (QTpD), and T peak to T end intervals (TpTe) of different lead configuration. An ECG vector magnitude signal based on 12-lead ECG was formed to estimate the global QT interval (vs. lead by lead QT interval used for calculating QT dispersion), also a robust algorithm for calculating the global T-peak to T-end interval (TpTe_VM) was created.
Results: The results based on the model simulation shows that the robust algorithm TpTe_VM based on the new robust algorithm is highly correlated with transmural dispersion of repolarization (TDR) with correlation coefficient of 0.97. The correlation coefficients for QTeD and QTpD with TDR are 0.53 and 0.82. And T peak dispersion of precordial leads has a correlation with interventricular dispersion (rr=0.84).
Conclusion: In conclusion, the Cell-to-ECG model provides is a very useful tool for studying electrophysiology and to link physiological factors to ECG morphology changes. The simulation results suggest that global T peak to T end interval can be a strong indicator of transmural dispersion of repolarization, and T peak dispersion has a good correlation with the interventricular dispersion.

(Abstract Control Number: 12)