Acute Changes in P-Wave Morphology by Pulmonary Vein Isolation in Atrial Fibrillation Patients

International audiencePulmonary vein (PV) plays an important role in atrial fibrillation (AF) initiation, progression, and stability. Successful PV isolation (PVI), either by radiofrequency catheter or Cryoballoon ablation, may terminate AF and prevent its recurrence. Whereas, incomplete PV isolation or reconnection of isolated PVs underlies mechanisms of AF recurrence. Hence, defining parameters able to predict a successful PVI and detect reconnections can assist clinicians in treatment of AF patients. Here, we developed a highly detailed human atrial model to simulate PVI and its acute effect on the P-wave morphology. Afterwards, the simulation results were compared and validated by recorded ECGs from patients before and after PVI procedure. In both simulation data and clinical recordings, we observed morphological changes in P-wave after PVI. More importantly our simulation helped us to find electrode positions in which the differences in P-wave morphology before and after PVI were more pronounced

Automatic Segmentation of Left Atrial Scar from Delayed-Enhancement Magnetic Resonance Imaging

Abstract. Delayed-enhancement magnetic resonance imaging is an effective technique for imaging left atrial (LA) scars both pre-and post-radio-frequency ablation for the treatment of atrial fibrillation. Existing techniques for LA scar segmentation require expert manual interaction making them tedious and prone to high observer variability. In this paper, we propose a novel automatic segmentation algorithm for segmenting LA scar based on a probabilistic tissue intensity model. This is implemented as a Markov random field-based energy formulation and solved using graph-cuts. It was evaluated against an existing semi-automatic approach and expert manual segmentations using 9 patient data sets. Surface representations were used to compare the methods. The segmented LA scar was expressed as a percentage of the total LA surface. Statistical analysis showed that the novel algorithm was not significantly different to the manual method and that it compared more favorably with this than the semi-automatic approach

Estimating the time scale and anatomical location of atrial fibrillation spontaneous termination in a biophysical model

Due to their transient nature, spontaneous terminations of atrial fibrillation (AF) are difficult to investigate. Apparently, confounding experimental findings about the time scale of this phenomenon have been reported, with values ranging from 1 s to 1 min. We propose a biophysical modeling approach to study the mechanisms of spontaneous termination in two models of AF with different levels of dynamical complexity. 8 s preceding spontaneous terminations were studied and the evolution of cycle length and wavefront propagation were documented to assess the time scale and anatomical location of the phenomenon. Results suggest that termination mechanisms are dependent on the underlying complexity of AF. During simulated AF of low complexity, the total process of spontaneous termination lasted 3,200 ms and was triggered in the left atrium 800 ms earlier than in the right atrium. The last fibrillatory activity was observed more often in the right atrium. These asymmetric termination mechanisms in both time and space were not observed during spontaneous terminations of complex AF simulations, which showed less predictable termination patterns lasting only 1,600 ms. This study contributes to the interpretation of previous clinical observations, and illustrates how computer modeling provides a complementary approach to study the mechanisms of cardiac arrhythmias

Signal reconstruction of pulmonary vein recordings using a phenomenological mathematical model: Application to pulmonary vein isolation therapy

This is the final version of the article. Available from Frontiers Media via the DOI in this record.Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is commonly initiated by ectopic beats originating from a small myocardial sleeve extending over the pulmonary veins. Pulmonary vein isolation therapy attempts to isolate the pulmonary veins from the left atrium by ablating tissue, commonly by using radiofrequency ablation. During this procedure, the cardiologist records electrical activity using a lasso catheter, and the activation pattern recorded is used as a guide toward which regions to ablate. However, poor contact between electrode and tissue ca n lead to important regions of electrical activity not being recorded in clinic. We reproduce these signals through the use of a phenomenological model of the cardiac action potential on a cylinder, which we fit to post-AF atrial cells, and model the bipolar electrodes of the lasso catheter by an approximation of the surface potential. The resulting activation pattern is validated by direct comparison with those of clinical recordings. A potential application of the model is to reconstruct the missing electrical activity, minimizing the impact of the information loss on the clinical procedure, and we present results to demonstrate this.JT acknowledges the generous support of the Wellcome Trust via Institutional Strategic Support Award (WT105618MA). JT further acknowledges financial support of the EPSRC via grant EP/N014391/1. HG acknowledges the financial support of the University of Exeter

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

Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue

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

Circ Res

Atrial fibrillation (AF) is the most common sustained arrhythmia in humans. The mechanisms that govern AF initiation and persistence are highly complex, of dynamic nature, and involve interactions across multiple temporal and spatial scales in the atria. This article aims to review the mathematical modeling and computer simulation approaches to understanding AF mechanisms and aiding in its management. Various atrial modeling approaches are presented, with descriptions of the methodological basis and advancements in both lower-dimensional and realistic geometry models. A review of the most significant mechanistic insights made by atrial simulations is provided. The article showcases the contributions that atrial modeling and simulation have made not only to our understanding of the pathophysiology of atrial arrhythmias, but also to the development of AF management approaches. A summary of the future developments envisioned for the field of atrial simulation and modeling is also presented. The review contends that computational models of the atria assembled with data from clinical imaging modalities that incorporate electrophysiological and structural remodeling could become a first line of screening for new AF therapies and approaches, new diagnostic developments, and new methods for arrhythmia prevention.DP1 HL123271/HL/NHLBI NIH HHS/United StatesDP1HL123271/DP/NCCDPHP CDC HHS/United States2015-04-25T00:00:00Z24763468PMC4043630vault:242

Modélisation d'arythmies auriculaires modulées par le système nerveux autonome

La fibrillation auriculaire (FA) est la forme d’arythmie la plus fréquente et représente environ un tiers des hospitalisations attribuables aux troubles du rythme cardiaque. Les mécanismes d’initiation et de maintenance de la FA sont complexes et multiples. Parmi ceux-ci, une contribution du système nerveux autonome a été identifiée mais son rôle exact demeure mal compris. Ce travail cible l’étude de la modulation induite par l’acétylcholine (ACh) sur l’initiation et le maintien de la FA, en utilisant un modèle de tissu bidimensionnel. La propagation de l’influx électrique sur ce tissu est décrite par une équation réaction-diffusion non-linéaire résolue sur un maillage rectangulaire avec une méthode de différences finies, et la cinétique d'ACh suit une évolution temporelle prédéfinie qui correspond à l’activation du système parasympathique. Plus de 4400 simulations ont été réalisées sur la base de 4 épisodes d’arythmies, 5 tailles différentes de région modulée par l’ACh, 10 concentrations d’ACh et 22 constantes de temps de libération et de dégradation d’ACh. La complexité de la dynamique des réentrées est décrite en fonction de la constante de temps qui représente le taux de variation d’ACh. Les résultats obtenus suggèrent que la stimulation vagale peut mener soit à une dynamique plus complexe des réentrées soit à l’arrêt de la FA en fonction des quatre paramètres étudiés. Ils démontrent qu’une décharge vagale rapide, représentée par des constantes de temps faibles combinées à une quantité suffisamment grande d’ACh, a une forte probabilité de briser la réentrée primaire provoquant une activité fibrillatoire. Cette activité est caractérisée par la création de plusieurs ondelettes à partir d’un rotor primaire sous l’effet de l’hétérogénéité du gradient de repolarisation causé par l’activité autonomique.Atrial fibrillation (AF) is the most frequent arrhythmia and accounts for about one-third of hospitalizations for cardiac rhythm disturbances. The mechanisms of initiation and maintenance of atrial fibrillation are complex and multifaceted. Among them, a contribution of the autonomic nervous system has been identified but its exact role remains poorly understood. This work targets the study of the effect of autonomic modulation induced by acetylcholine (ACh) on the initiation and maintenance of AF, using a two-dimensional tissue model. Electrical impulse propagation in the tissue was described by as a non-linear reaction-diffusion equation solved on a rectangular mesh with finite difference methods, and ACh kinetics followed a predefined time evolution corresponding to parasympathetic activation. More than 4400 simulations were performed based on 4 fibrillatory initial conditions, 5 sizes of ACh patch, 10 ACh concentrations and 22 time constants representing ACh release and degradation speed. Our results suggest that vagal stimulation can sustain or terminate AF depending on the 4 parameters studied. Results demonstrate that rapid vagal discharge, represented by low time constants combined with sufficient quantities of ACh, has a high probability of breaking the primary reentry and causing fibrillatory activity. This activity is characterized by the generation of several wavelets from a primary rotor under the heterogeneity of repolarization gradient due to autonomic modulation

Modélisation de l’activité électrique des oreillettes avant et après ablation par cathéter

- Réalisé au centre de recherche de l'hospital du Sacré-Coeur de Montréal. - Programme conjoint entre Université de Montréal et École Polytechnique de Montréal.La fibrillation auriculaire (FA) est la forme d’arythmie la plus fréquente chez les êtres humains. Les mécanismes qui gouvernent l’initiation et les manifestations de cette maladie sont complexes, de nature dynamique, incluant des interactions à travers multiples échelles temporelles et spatiales dans les oreillettes. Ceci conduit très souvent à des manifestations imprévisibles et à des phénomènes qui émergent à l’échelle de l’organe, et qui se reflètent à l’échelle de tout le torse. Pour remédier à ce problème, on peut effectuer une ablation par cathéter, qui consiste à créer sur le tissu auriculaire des lésions linéaires qui bloquent et contraignent la propagation électrique. Parfois, ces lignes se reconnectent quelque temps après l’intervention, ce qui mène à des récidives, nécessitant ainsi une nouvelle intervention. Le but de ce projet est de modéliser un suivi de l’onde P post-opératoire pour détecter de manière non-invasive la reconnexion des lignes d’ablation et ainsi prédire les récidives de fibrillation auriculaire. À l’aide d’un modèle mathématique des oreillettes et du thorax, les ondes P sont simulées avant et après ablation, ainsi qu’après reconnexion de certaines lignes d’ablation. Les résultats montrent que la morphologie et les caractéristiques de l’onde P, ainsi que la carte d’activation sont affectées significativement par l’ablation et les reconnexions subséquentes. Ces différences sont plus facilement détectables lorsque les reconnexions naissent sur la veine pulmonaire inférieure gauche. Les changements sont plus importants pour les électrodes placées sur certaines zones du torse, notamment dans le dos. Ces nouvelles données aident actuellement à la conception d’une étude clinique pour valider l’approche.Atrial fibrillation (AF) is the most common form of arrhythmia in humans. The mechanisms governing the initiation and manifestations of that disease are complex, dynamic in nature, including interactions across multiple spatial and temporal scales in the atria. This often leads to unpredictable manifestations and phenomena that arise at the level of the organ, and are reflected across the entire torso. To remedy that problem, catheter ablation can be carried out, which consists in creating linear lesions which block and force the electrical propagation in the atrial tissue. Sometimes these lines reconnect after the procedure, which leads to atrial fibrillation recurrence, thus requiring a new intervention. The purpose of this work is to model the monitoring of the postoperative P wave to detect non-invasively the reconnection of ablation lines and to predict atrial fibrillation recurrences. Using a mathematical model of the atria and thorax, the P waves are simulated before and after ablation, as well as after reconnection of some ablation lines. The results show that the morphology and the characteristics of the P wave as well as the activation map are significantly affected by the ablation lines and the subsequent reconnections. These differences are more easily detected when reconnections arise on the left inferior pulmonary vein. The changes are most important in electrodes placed in certain areas of the torso, notably in the back. These new data are helping to plan a clinical study to validate the approach