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.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.
Multiscale cardiac modeling has made great advances over the last decade. Highly detailed atrial models were created and used for the investigation of initiation and perpetuation of atrial fibrillation. The next challenge is the use of personalized atrial models in clinical practice. In this study, a framework of simple and robust tools is presented, which enables the generation and validation of patient-specific anatomical and electrophysiological atrial models. Introduction of rule-based atrial fiber orientation produced a realistic excitation sequence and a better correlation to the measured electrocardiograms. Personalization of the global conduction velocity lead to a precise match of the measured P-wave duration. The use of a virtual cohort of nine patient and volunteer models averaged out possible model-specific errors. Intra-atrial excitation conduction was personalized manually from left atrial local activation time maps. Inclusion of LE-MRI data into the simulations revealed possible gaps in ablation lesions. A fast marching level set approach to compute atrial depolarization was extended to incorporate anisotropy and conduction velocity heterogeneities and reproduced the monodomain solution. The presented chain of tools is an important step towards the use of atrial models for the patient-specific AF diagnosis and ablation therapy planing.
Complex fractionated atrial electrograms (CFAE) are a target for catheter ablation as they coincide with areas of slow conduction. In this study we simulated different vol- ume fractions of diffuse and patchy fibrosis up to 50 %. Catheter signals for different electrode spacings were cal- culated and characteristic features were compared to a clinical database of CFAE-signals. A linear slowing of global conduction velocities was found independent of the type of fibrosis. For patchy fibrosis, electrograms displayed fractionation, which was not seen for diffuse fibrosis of the same degree. In comparison to clinical data, simulated electrograms showed up to 10 zero crossings per electro- gram, which was also seen for clinical EGMs with medium fractionation (class 2 of 3). For both, clinical (84 %) and simulated (88 %) signals, a significant difference in ampli- tude is present between fractionated and non-fractionated signals.
Creating transmural ablation scars in a reliable way is a key issue in improvement of therapeutical pro- cedures for cardiac arrhythmias. About one third of the patients has to undergo several procedures till arrhythmic episodes are successfully treated. Morphological features of intracardiac electrograms might contribute to evaluate scar transmurality during the ablation procedure. We an- alyzed intracardiac signals before, during and after point- wise ablation in patients with atrial flutter. Unipolar elec- trograms of the distal electrode showed a relative decrease in amplitude of the second extremum of up to 99 % with a mean of 84±20.6 % after the endpoint of ablation.
Intracardiac electrograms are the key in under- standing, interpretation and treatment of cardiac arrhythmias. However, electrogram morphologies are strongly variable due to catheter position, orientation and contact. Simulations of intracardiac electrograms can improve comprehension and quantification of influencing parameters and therefore reduce misinterpretations. In this study simulated intracardiac electro- grams are analyzed regarding tilt angles of the catheter relative to the propagation direction, electrode tissue distances as well as clinical filter settings. Catheter signals are computed on a realistic 3D catheter geometry using bidomain simulations of cardiac electrophysiology. Thereby high conductivities of the catheter electrodes are taken into account. For validation, simulated electrograms are compared with in vivo electrograms recorded during an EP-study with direct annotation of catheter orientation and tissue contact. Good agreement was reached regarding timing and signal width of simulated and measured electrograms. Correlation was 0.92±0.07 for bipolar, 0.92±0.05 for unipolar distal and 0.80 ± 0.12 for unipolar proximal electrograms for different catheter orientations and locations.
Local activation time (LAT) maps help to understand the path of electrical excitation in cardiac arrhythmias. They can be generated automatically from intracardiac electrograms using various criteria provided by commercial electroanatomical mapping systems. This study compares existing criteria and a novel method based on the non-linear energy operator (NLEO) with respect to their precision and robustness.
Intracardiac electrograms are essential for the diagnosis and treatment of various cardiac arrhythmias. To gain reliable information about structural alterations of underlying tissue, it is necessary to interpret these electrograms correctly. Therefore it has to be understood how other parameters influence the signal. Realistic 3D geometries were created and simulated using the bidomain model. Based on these simulations, the influences of catheter orientation, tissue thickness and conduction velocity on the amplitudes of intracardiac electrograms were evaluated.
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.