Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity

It has become widely accepted that the most dangerous cardiac arrhythmias are due to re- entrant waves, i.e., electrical wave(s) that re-circulate repeatedly throughout the tissue at a higher frequency than the waves produced by the heart's natural pacemaker (sinoatrial node). However, the complicated structure of cardiac tissue, as well as the complex ionic currents in the cell, has made it extremely difficult to pinpoint the detailed mechanisms of these life-threatening reentrant arrhythmias. A simplified ionic model of the cardiac action potential (AP), which can be fitted to a wide variety of experimentally and numerically obtained mesoscopic characteristics of cardiac tissue such as AP shape and restitution of AP duration and conduction velocity, is used to explain many different mechanisms of spiral wave breakup which in principle can occur in cardiac tissue. Some, but not all, of these mechanisms have been observed before using other models; therefore, the purpose of this paper is to demonstrate them using just one framework model and to explain the different parameter regimes or physiological properties necessary for each mechanism (such as high or low excitability, corresponding to normal or ischemic tissue, spiral tip trajectory types, and tissue structures such as rotational anisotropy and periodic boundary conditions). Each mechanism is compared with data from other ionic models or experiments to illustrate that they are not model-specific phenomena. The fact that many different breakup mechanisms exist has important implications for antiarrhythmic drug design and for comparisons of fibrillation experiments using different species, electromechanical uncoupling drugs, and initiation protocols.Comment: 128 pages, 42 figures (29 color, 13 b&w

Theory, modelling and applications of electrocardiographic mapping

In this thesis, the genesis and applications of electromagnetic signals from the human heart are investigated through theory, modelling, signal processing and clinical studies. One objective of the thesis was to develop and test signal processing methods that would be applicable to multichannel electro- and magnetocardiographic data. A signal processing method based on a type of neural networks called the self-organizing maps is introduced for spatiotemporal analysis of the body surface potential maps produced by the beating heart. This method is capable of utilizing both the spatial morphology of the potential distributions on the body surface as well as their temporal development. A signal processing method aimed at providing a reliable electric baseline for more traditional isointegral analysis of the body surface potential mapping (BSPM) data is also introduced. Another objective of the thesis was to show the utility of electrocardiographic mapping in clinical use. This was demonstrated by applying electro- and magnetocardiographic mapping to evaluation of the propensity to life-threatening arrhythmias in postinfarction patients. Electrocardiographic mapping was found to perform equally well compared to more traditional SA-ECG, but electrocardiographic mapping may be more robust against individual variability in anatomy. A third objective of the thesis was to build a computer model of the human heart that is capable of simulating the normal ventricular activation. The propagation model is based on a bidomain formulation of the cardiac tissue applied to realistic geometry of the ventricles. An anatomically accurate model of the human conduction system that reproduces measured activation sequence of the human heart was developed in this thesis. The body surface potentials and the magnetic fields computed from the simulated activation corresponded to recordings from normal subjects. In summary, the thesis demonstrates the utility of electrocardiographic mapping in clinical use and introduces new signal processing methods that can be applied to this use. Finally, a computer model of the human heart binds together the physiology and anatomy of the human heart and body, classical electromagnetic theory, and computer science to explain the genesis and characteristics of the electromagnetic signals from the human heart.reviewe

Caractérisation et traitement du substrat électrique pour la thérapie de resynchronisation cardiaque

We aimed to characterize the electrical substrate amenable to biventricular pacing (BVP) and to assess the actual value of electrical resynchronization. We showed, both with respect to surface ECG and detailed ventricular electrocardiographic mapping (ECM), a strong relationship between the baseline electrical dyssnchrony and the hemodynamic response to BIV pacing. Compared with standard ECG, ECM allows a more detailed analysis of the ventricular dyssynchrony and better predicts clinical outcomes after BVP. A minimal amount of electrical dyssynchrony, in particular a sufficient LV activation delay relative to right ventricular activation, is a prerequisite to the hemodynamic response to BVP. Due to their advanced electrical dyssynchrony, patients with left bundle branch block present potential for BVP positive response which acts by electrical resynchronization. Conversely, BVP worsens the electrical activation (iatrogenic dyssynchrony) and hemodynamics in patients with narrow QRS suffering from insufficient electrical dyssynchrony at baseline. Patients with unspecified conduction disorders show variable levels of electrical dyssynchrony and as a consequence mixed results to BVP. Similarly, ECM reveals a variable degree of left ventricular activation delay in patients chronically paced in the right ventricle. Beside the electrical resynchronization, other mechanisms are involved in the cardiac pump function improvement such as the redistribution of the mechanical work over the right and left ventricles. Through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by single site LV pacing.L'objectif de ce travail était de mieux appréhender les mécanismes impliqués dans la réponse à la resynchronisation biventriculaire (BIV) en insistant sur la caractérisation du substrat électrique éligible à la thérapie et l'intérêt de la resynchronisation électrique. Nous avons démontré qu'il existe une relation forte entre l'asynchronisme électrique de base défini tant par l'ECG de surface que par cartographie détaillée de l'activation ventriculaire (ECM) et la réponse hémodynamique à la stimulation BIV. Par rapport à l'ECG de surface, l'ECM permet une caractérisation plus fine de l'asynchronisme électrique ventriculaire avec une meilleure prédiction de la réponse clinique à la stimulation BIV. La présence d'un asynchronisme de base minimum, en particulier d'un retard d'activation ventriculaire gauche (VG) par rapport au ventricule droit (typiquement >SOms), est un prérequis à l'efficacité de la thérapie. Les patients avec bloc de branche gauche présentent un haut degré d'asynchronisme et la stimulation BIV agit sur ce substrat par resynchronisation de l'activation électrique. A contrario, la stimulation BIV dégrade la séquence d'activation ainsi que l'hémodynamique des patients à QRS fins (dyssynchronie iatrogène). Les patients présentant un trouble de conduction aspécifique présentent des degrés variables d'asynchronie électrique et en conséquence des réponses contrastées à la stimulation BIV. De même, l'analyse ECM de l'asynchronisme des patients chroniquement stimulés sur le ventricule droit a permis de mettre en évidence des degrés variables de retard d'activation du VG. Si la resynchronisation électrique est garante d'une amélioration de la fonction cardiaque, d'autres mécanismes sont impliqués telle la redistribution du travail segmentaire au sein du myocarde ventriculaire. L'efficacité de la stimulation mono-VG implique une participation accrue du ventricule droit au travail global (interaction ventriculaire)

2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias

2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias

New Engineering Approaches to Arrhythmias and Myocardial Infarction

In this thesis, we present new engineering approaches to several important cardiac diseases. Chapter 1 considers the dynamics of arrhythmias. The most dangerous arrhythmias are reentrant arrhythmias, including ventricular fibrillation and ventricular tachycardia. During these arrhythmias, there are one or several rotating excitation waves present in the heart. Because of their shape, these waves are called scroll waves; their center of rotation is a one-dimensional curve called the filament. Filaments largely constrain the configuration of a scroll wave but are much simpler, so much effort has gone into describing scroll wave dynamics in terms of the dynamics of their filaments. In particular, the “geodesic principle” for filaments, which says that stable filaments are geodesics in a metric derived from the diffusivity, has been proposed and established for certain restrictive conditions. In this project, we show that the geodesic principle applies much more broadly, including for very large filament curvatures. We also discuss under which conditions the geodesic principle fails, particularly the case that the filament gets close to very heterogeneous substrate. Chapters 2-4 introduce a new approach to cardiac defibrillation. The only existing effective treatment to ventricular fibrillation is to deliver high-energy electric shocks to the heart using a defibrillator to terminate fibrillation and restore organized rhythm. Defibrillators currently available are effective in treating ventricular fibrillation, however, because of the large amount of energy deposited during the treatment can cause damaging effects to the tissue. In this project, we present results of a new technology using nanosecond pulsed electric fields to defibrillate the heart, while depositing only a fraction of energy needed by conventional defibrillators. In the final part of this thesis, Chapters 5-7, we present results of an injectable therapeutic agent to regenerate the myocardium (heart muscle) affected by infarction. Myocardial infarction is a serious coronary artery disease that occurs when a coronary artery is so severely blocked that there is a dramatic reduction or complete disruption of blood supply, causing damage or death to the territory of the myocardium that was supplied by the blocked coronary vessel. Our results show how the injection of the therapeutic agent helps in preserving the electrical activity in the affected area, and also reduces pathological effects on the ejection fraction and heart rate. In summary, we contribute to the understanding of the mechanisms of reentrant arrhythmias, develop new technology for ventricular defibrillation, and test a therapeutic agent for myocardial infarction