Abstract:

Congenital Long-QT Syndrome (LQTS) is a genetic dis- order affecting the repolarization of the heart. The most prevalent subtypes of LQTS are LQT1-3. In this work, we aim to evaluate the differences in the T-waves of simu- lated LQT1-3 in order to identify markers in the ECG that might help to classify patients solely based on ECG mea- surements. For LQT1, mutation S277L was used to char- acterize IKs and mutation S818L in IKr for LQT2. Volt- age clamp data were used to parametrize the ion channel equations of the ten Tusscher and Panfilov model of hu- man ventricular electrophysiology. LQT3 was integrated using an existing mutant INa model. The monodomain model was used in a transmural and apico-basal heteroge- neous model of the ventricles to calculate ventricular exci- tation propagation. The forward calculation on a torso model was performed to determine body surface ECGs. Compared to the physiological case with a QT-time of 375 ms, this interval was prolonged in all LQTS (LQT1 423 ms; LQT2 394 ms; LQT3 405 ms). The T-wave ampli- tude was changed (Einthoven lead II: LQT1 108%; LQT2 91%; LQT3 103%). Also, the width of the T-wave was en- larged (full width at half maximum: LQT1 111%; LQT2 125%; LQT3 109%). At the current state of modeling and data analysis, the three LQTS have not been distinguish- able solely by ECG data.

Abstract:

Heterogeeities of the ventricular electrophysiol- ogy play a major role in the generation of the T-wave mor- phology and amplitude. The exact way of the distribution of electrophysiological differences is not known. In this work, a numerical approach is presented in which the excitation propagation of different heterogeneity distributions of IKs are simulated and the multi-channel ECG is calculated. The ECG data are evaluated against measured ECGs. The most realistic configuration is a combination of transmural and apico-basal heterogeneity with 35% of Endo, 30% of M and 35% of Epi cells and an apico-basal gradient with a factor of 2. This specific setup has a correlation of around 90% and a root mean square error of around 0.0795.