BUNDLE BRANCH BLOCKS SIMULATIONS IN VENTRICULAR MODEL WITH REALISTIC GEOMETRY AND CONDUCTION SYSTEM

The goal of the study was to design a model of cardiac ventricles with realistic geometry that enables simulation of the ventricular activation with normal conduction system functions, as well as with bundle branch blocks. In ventricles, electrical activation propagates from the His bundle to the left and right bundle branches and continues to the fascicles and branching fibers of the Purkinje system. The role of these parts of the conduction system is to lead the activation rapidly and synchronously to the left and right ventricle. The velocity of propagation in the conduction system is several times higher than in the surrounding ventricular myocardium. If the conduction system works normally, QRS duration representing the total activation time of the ventricles lies in the physiological range of about 80 to 120 ms but it is more than 120 ms in the case of bundle branch blocks. In our study, the realistic geometry of the ventricles was constructed on the base of a patient CT scan, defining epicardial and endocardial surfaces. The first part of the conduction system (fast-conducting bundle branches, fascicles in the left ventricle and initial parts of the Purkinje fibers) was modeled as polyline pathways isolated from the surrounding ventricular tissue. The remaining part of the Purkinje system was modeled as an endocardial layer with higher conduction velocity. The propagation of the electrical activation in the ventricular model was modeled using reaction-diffusion (RD) equations, except for the first part of the conduction system, where the activation times were evaluated algebraically with respect to predefined velocity of propagation and estimated distance between the His bundle and particular entry point to the layer with higher conduction velocity. Propagation of activation in cardiac ventricles was numerically solved in Comsol Multiphysics environment. Several configurations of the first part of the conduction system with different number of polyline pathways and entry points were proposed and tested to achieve realistic activation propagation. For the model with 9 starting points, realistic total activation time (TAT) of the whole ventricles of about 108 ms was obtained for the model with normal conduction system, and realistic TAT of 126 ms and 149 ms were obtained for the right and left bundle branch block (RBBB, LBBB), respectively. Very similar TAT was found also for the model with 7 starting points, but unrealistically long TAT was obtained in LBBB simulation for the model with only 5 starting points

The Effect of Segmentation Variability in Forward ECG Simulation

International audienceSegmentation of patient-specific anatomical models is one of the first steps in Electrocardiographic imaging (ECGI). However, the effect of segmentation variability on ECGI remains unexplored. In this study, we assess the effect of heart segmentation variability on ECG simulation. We generated a statistical shape model from segmentations of the same patient and generated 262 cardiac geometries to run in an ECG forward computation of body surface potentials (BSPs) using an equivalent dipole layer cardiac source model and 5 ventricular stimulation protocols. Variability between simulated BSPs for all models and protocols was assessed using Pearson's correlation coefficient (CC). Compared to the BSPs of the mean cardiac shape model, the lowest variability (average CC = 0.98 ± 0.03) was found for apical pacing whereas the highest variability (average CC = 0.90 ± 0.23) was found for right ventricular free wall pacing. Furthermore, low amplitude BSPs show a larger variation in QRS morphology compared to high amplitude signals. The results indicate that the uncertainty in cardiac shape has a significant impact on ECGI

Noninvasive mapping of repolarization:Validation in healthy and diseased hearts

The initiation and maintenance of (reentrant) arrhythmias is facilitated by local heterogeneities in cardiac activation and repolarization. Detection of these heterogeneities by cardiac mapping is important for guiding local therapy and for early risk stratification of patients, and is presently mostly performed by invasive techniques. A non-invasive method for localization of functional heterogeneities may help the treatment of patients with life threatening ventricular arrhythmias, may support risk stratification and may help to reduce mortality caused by these arrhythmias. This thesis investigates a non-invasive method to determine and localize functional repolarization heterogeneities based on potentials measured at the body surface. It demonstrates that parameters that highlight multiple repolarization moments in the standard 12-lead ECG, better characterize the underlying repolarization gradient than the single time point of latest global repolarization (QTtime). For further localization of possible heterogeneities, this thesis uses the equivalent dipole layer (EDL) method for the solution of the inverse problem of electrocardiography; the mathematical reconstruction of cardiac electrical activity from body surface electrograms and a geometric model of the torso. The accuracy was investigated in in-silico, ex-vivo, and in-vivo settings, showing good correlations with gold standard repolarization times, even in the presence of noise, abnormal repolarization or myocardial infarction. In addition, comparison of the EDL method with the more commonly used epicardial potential (EP) method shows that both methods provide accurate reconstruction of cardiac activation and repolarization patterns and beat origins, with the EDL method showing a better correlation for activation timings and beat origins than the EP method. Although the use of this technique for noninvasive mapping of repolarization is promising, we provide directions for future research to improve accuracy of inverse reconstruction

In silico validation of electrocardiographic imaging to reconstruct the endocardial and epicardial repolarization pattern using the equivalent dipole layer source model

The solution of the inverse problem of electrocardiology allows the reconstruction of the spatial distribution of the electrical activity of the heart from the body surface electrocardiogram (electrocardiographic imaging, ECGI). ECGI using the equivalent dipole layer (EDL) model has shown to be accurate for cardiac activation times. However, validation of this method to determine repolarization times is lacking. In the present study, we determined the accuracy of the EDL model in reconstructing cardiac repolarization times, and assessed the robustness of the method under less ideal conditions (addition of noise and errors in tissue conductivity). A monodomain model was used to determine the transmembrane potentials in three different excitationrepolarization patterns (sinus beat and ventricular ectopic beats) as the gold standard. These were used to calculate the body surface ECGs using a finite element model. The resulting body surface electrograms (ECGs) were used as input for the EDLbased inverse reconstruction of repolarization times. The reconstructed repolarization times correlated well (COR > 0.85) with the gold standard, with almost no decrease in correlation after adding errors in tissue conductivity of the model or noise to the body surface ECG. Therefore, ECGI using the EDL model allows adequate reconstruction of cardiac repolarization times

Patient-Specific Identification of Atrial Flutter Vulnerability–A Computational Approach to Reveal Latent Reentry Pathways

Atypical atrial flutter (AFlut) is a reentrant arrhythmia which patients frequently develop after ablation for atrial fibrillation (AF). Indeed, substrate modifications during AF ablation can increase the likelihood to develop AFlut and it is clinically not feasible to reliably and sensitively test if a patient is vulnerable to AFlut. Here, we present a novel method based on personalized computational models to identify pathways along which AFlut can be sustained in an individual patient. We build a personalized model of atrial excitation propagation considering the anatomy as well as the spatial distribution of anisotropic conduction velocity and repolarization characteristics based on a combination of a priori knowledge on the population level and information derived from measurements performed in the individual patient. The fast marching scheme is employed to compute activation times for stimuli from all parts of the atria. Potential flutter pathways are then identified by tracing loops from wave front collision sites and constricting them using a geometric snake approach under consideration of the heterogeneous wavelength condition. In this way, all pathways along which AFlut can be sustained are identified. Flutter pathways can be instantiated by using an eikonal-diffusion phase extrapolation approach and a dynamic multifront fast marching simulation. In these dynamic simulations, the initial pattern eventually turns into the one driven by the dominant pathway, which is the only pathway that can be observed clinically. We assessed the sensitivity of the flutter pathway maps with respect to conduction velocity and its anisotropy. Moreover, we demonstrate the application of tailored models considering disease-specific repolarization properties (healthy, AF-remodeled, potassium channel mutations) as well as applicabiltiy on a clinical dataset. Finally, we tested how AFlut vulnerability of these substrates is modulated by exemplary antiarrhythmic drugs (amiodarone, dronedarone). Our novel method allows to assess the vulnerability of an individual patient to develop AFlut based on the personal anatomical, electrophysiological, and pharmacological characteristics. In contrast to clinical electrophysiological studies, our computational approach provides the means to identify all possible AFlut pathways and not just the currently dominant one. This allows to consider all relevant AFlut pathways when tailoring clinical ablation therapy in order to reduce the development and recurrence of AFlut

ECGSIM: un programma per la simulazione interattiva di tracciati ECG a scopo didattico e di ricerca.

ECGSIM è un simulatore interattivo utile allo studio e alla comprensione delle relazioni tra le attività elettriche delle cellule miocardiche e i potenziali elettrici registrati tramite elettrodi sulla superficie cutanea del corpo umano. Con ECGSIM è possibile modificare i parametri di attivazione di nodi sulla superficie del cuore, del quale viene mostrata una immagine tridimensionale, e verificarne gli effetti sui tracciati ECG. Sono presenti pannelli che mostrano cuore, torace, potenziale del nodo selezionato sul cuore e tracciati ECG. Finestre e comandi appositi consentono di agire su diversi parametri, come i tempi di depolarizzazione, ripolarizzazione e plateau delle cellule miocardiche. Uno degli scopi principali di ECGSIM è quello di fornire uno strumento per l’apprendimento da parte degli studenti dei fondamenti dell’elettrocardiografia, sia per lo studio individuale che come supporto all'insegnamento in aula. Può essere utilizzato anche come strumento di ricerca da tutti coloro che vogliono testare le ipotesi di patologie cardiache come possibile causa di anomalie nel tracciato ECG

Patient-Specific Identification of Atrial Flutter Vulnerability–A Computational Approach to Reveal Latent Reentry Pathways

Atypical atrial flutter (AFlut) is a reentrant arrhythmia which patients frequently develop after ablation for atrial fibrillation (AF). Indeed, substrate modifications during AF ablation can increase the likelihood to develop AFlut and it is clinically not feasible to reliably and sensitively test if a patient is vulnerable to AFlut. Here, we present a novel method based on personalized computational models to identify pathways along which AFlut can be sustained in an individual patient. We build a personalized model of atrial excitation propagation considering the anatomy as well as the spatial distribution of anisotropic conduction velocity and repolarization characteristics based on a combination of a priori knowledge on the population level and information derived from measurements performed in the individual patient. The fast marching scheme is employed to compute activation times for stimuli from all parts of the atria. Potential flutter pathways are then identified by tracing loops from wave front collision sites and constricting them using a geometric snake approach under consideration of the heterogeneous wavelength condition. In this way, all pathways along which AFlut can be sustained are identified. Flutter pathways can be instantiated by using an eikonal-diffusion phase extrapolation approach and a dynamic multifront fast marching simulation. In these dynamic simulations, the initial pattern eventually turns into the one driven by the dominant pathway, which is the only pathway that can be observed clinically. We assessed the sensitivity of the flutter pathway maps with respect to conduction velocity and its anisotropy. Moreover, we demonstrate the application of tailored models considering disease-specific repolarization properties (healthy, AF-remodeled, potassium channel mutations) as well as applicabiltiy on a clinical dataset. Finally, we tested how AFlut vulnerability of these substrates is modulated by exemplary antiarrhythmic drugs (amiodarone, dronedarone). Our novel method allows to assess the vulnerability of an individual patient to develop AFlut based on the personal anatomical, electrophysiological, and pharmacological characteristics. In contrast to clinical electrophysiological studies, our computational approach provides the means to identify all possible AFlut pathways and not just the currently dominant one. This allows to consider all relevant AFlut pathways when tailoring clinical ablation therapy in order to reduce the development and recurrence of AFlut

Application of the fastest route algorithm in the interactive simulation of the effect of local ischemia on the ECG

A method is described to determine the effect on the ECG of a reduced propagation velocity within an ischemic zone. The method was designed to change the activation sequence throughout the ventricles interactively, i.e. with a response time in the order of a second. The timing of ventricular ischemic activation was computed by using the fastest route algorithm, based on locally reduced values of the propagation velocities derived from a standard, normal activation sequence. The effect of these local reductions of the velocities on the total activation sequence, as well as the changes in the electrocardiogram that these produce, are presented