There is a growing consensus that life-threatening cardiac arrhythmias like ventricular tachycardia (VT) or ventricular fibrillation (VF) arise because of the formation of spiral waves of electrical activation in cardiac tissue; unbroken spiral waves are associated with VT and broken ones with VF. Several experimental studies have shown that inhomogeneities in cardiac tissue can have dramatic effects on such spiral waves. In this thesis we try to understand these experimental results by carrying out detailed and systematic studies of the interaction of spiral waves with different types of inhomogeneities in mathematical models for cardiac tissue. In Chapter 1 we begin with a general introduction to cardiac arrhythmias, the cardiac conduction system, and the connection between electrical activation waves in cardiac tissue and cardiac arrhythmias. As we have noted above, VT and VF are believed to be associated with spiral waves of electrical activation on cardiac tissue; such spiral waves form because cardiac tissue is an excitable medium. Thus we give an overview of excitable media, in which sub-threshold perturbations decay but super-threshold perturbations lead to an action potential that consists of a rapid stage of depolarization of cardiac cells followed by a slow phase of repolarization. During this repolarization phase the cells are refractory. We then give an overview of earlier studies of the effects of inhomogeneities in cardiac tissue; and we end with a brief description of the principal problems we study here. Chapter 2 describes the models we use in our work. We start with a general introduction to the cable equation and then discuss the Hodgkin-Huxley-formalism for the transport of ions across a cell membrane through voltage-gated ion channels. We then describe in detail the three models that we use for cardiac tissue, which are, in order of increasing complexity, the Panfilov model, the Luo Rudy Phase I (LRI) model, and the reduced Priebe Beuckelmann (RPB)model. We then give the numerical schemes we use for solving these model equations and the initial conditions that lead to the formation of spiral waves. For all these models we give representative results from our simulations and compare the states with spiral turbulence. In Chapter 3 we investigate the effects of conduction inhomogeneities (obstacles) in the three models introduced in Chapter 2. We outline first the experimental results that have provided the motivation for our study. We then discuss how we introduce obstacles in our simulations of the Panffilov, LRI, and RPB models for cardiac tissue. Next we present the results of our numerical studies of the effects, on spiral-wave dynamics, of the sizes, shapes, and positions of the obstacles. Our Principal result is that spiral-wave dynamics in these models depends sensitively on the position of the obstacle. We find, in particular, that, merely by changing the position of a conduction inhomogeneity, we may convert spiral turbulence (the analogue in our models of VF) to a single rotating spiral (the analogue of VT) anchored to the obstacle or vice versa; even more exciting is the possibility that, at the boundary between these two types of behaviour, we find a quiescent state Q with no spiral waves. Thus our study obtains all the possible qualitative behaviours found in experiments, namely, (1) VF might persist even in the presence of an obstacle, (2) it might be suppressed partially and become VT, or (3) it might be eliminated completely. In Chapter 4 we extend our work on conduction inhomogeneities (Chapter 3) to ionic inhomogeneities. Unlike conduction inhomogeneities, ionic inhomogeneities allow the conduction of activation waves. We find, nevertheless, that they too can lead to the anchoring of spiral waves or even the complete elimination of spiral-wave turbulence. Since spiral waves can enter the region in which there is an ionic inhomogeneity, their behaviours in the presence of such an inhomogeneity are richer than those with conduction inhomogeneities. We find, in particular, that a single spiral wave anchored at an ionic inhomogeneity can show temporal evolution that may be periodic, quasiperiodic, or even chaotic. In the last case the spiral wave shows a chaotic pattern inside the ionic inhomogeneity and a regular one outside it. Defibrillation is the control of arrhythmias such as VF. Most often defibrillation is effected electrically by administering a shock, either externally or via an internally implanted defibrillator. The development of low-amplitude defibrillation schemes, which minimise the deleterious effects of the applied shock, is a major challenge in the treatment of cardiac arrhythmias. Numerical studies of models for cardiac tissue provide us with convenient means of studying the elimination of spiral-wave turbulence by the application of external electrical stimuli; this is the numerical analogue of defibrillation. Over the years some low-amplitude defibrillation schemes have been suggested on the basis of such numerical studies. In Chapter 5 we discuss two such schemes that have been shown to suppress spiral-wave turbulence in two-dimensional models for cardiac tissue and also scroll-wave turbulence in three-dimensional models. One of these schemes uses local electrical pacing, typically in the centre of the simulation domain; the other applies the external electrical stimuli over a mesh. We study the efficacy of these schemes in the presence of conduction inhomogeneities. We find, in particular, that the local-pacing scheme, though effective in a homogeneous simulation domain, fails to control spiral turbulence in the presence of an obstacle and, indeed, might even facilitate spiral-wave break up. By contrast, the second scheme, which uses a mesh, succeeds in eliminating spiral-wave turbulence even in the presence of an obstacle. We end with some concluding remarks about the possible experimental implications of our study in Chapter 6.

Les arythmies ventriculaires conduisant à la mort subite ont été précédemment associées àun type de cellules spécialisées, les fibres de Purkinje (FP). Elles font partie du systèmede conduction cardiaque, et possèdent un rôle majeur dans l’impulsion électrique et l’activationsynchrone des ventricules. Néanmoins, elles peuvent être impliquées dans des phénomènespro-arythmogéniques à l’origine de l’initiation ou du maintien de la fibrillation ventriculaire(FV) au sein de structures normales ou dans le cas d’un large spectre de maladies cardiaques.Cependant, les caractéristiques électrophysiologiques et structurelles des FP etles mécanismes sous-jacents des arythmies liées au Purkinje restent inconnus. Le systèmePurkinje semblerait jouer un rôle important de substrat de l’arythmie en raison de son impactsur l’hétérogénéité transmurale de repolarisation.Six études décrivant les propriétés électrophysiologiques et les propriétés macro/microstructurellesde ventricules gauches de brebis et de ventricules gauches humains ont étédéveloppées en utilisant une combinaison de méthodes classiques et innovantes.Les résultats ont permis de montrer que les FP, à travers leurs jonctions avec le myocarde,modulaient localement la durée du potentiel d'action et jouaient un rôle dans la dispersionde la repolarisation, révélant ainsi le rôle potentiel des FP dans le déclenchement etle maintien de la FV.Ce travail ouvre de nouvelles perspectives thérapeutiques dans le traitement préventifde l'arythmie ventriculaire afin de lutter contre la mort subite d'origine cardiaque. / Arrhythmias that lead to sudden death have previously been associated with a specializedcell type, the Purkinje fibers (PF). They form the cardiac conduction system, and have a majorrole in the electrical impulse and synchronous activation of the ventricles. However, they maybe involved in pro-arrhythmic phenomena causing the initiation or maintenance of ventricularfibrillation (VF) in structurally normal and a broad spectrum of cardiac diseases.Nevertheless, electrophysiological and structural characteristics of PF and mechanismsunderlying Purkinje-related arrhythmias are poorly understood. It is hypothesized thatthe Purkinje system plays an important role as a substrate for arrhythmias due to, in part,its impact on transmural repolarization heterogeneity.Here within are six studies describing electrophysiological and macro/micro structuralproperties of sheep and human left ventricles using a combination of conventional andinnovative methods.Results showed that PF, through junctions with the myocardium, locally modulatedthe action potential duration and played a role in the dispersion of repolarization. Therefore,revealing a potential role for PF in both, trigger and maintenance of VF.This work opens new therapeutic perspectives in preventive treatment of ventriculararrhythmia to fight against sudden cardiac death.

No description available.

The theme for this thesis is based on the European Resuscitation Council's guidelines for cardiopulmonary resuscitation of 2015. One of the important points of these procedures is the use of an automatic external defibrillator (AED). These devices were developed for informed responders without the knowledge of cardiac rhythm diagnostics and allow to perform an early defibrillation of the heart, before the arrival of emergency services. AED is a sophisticated device that is a part of the equipment of I - firefighters and policemen. Training of these so-called first aid responders performs the local emergency service team. Over the years 2015 and 2016, the majority of the professionally active firefighters and police officers in one selected Czech district who have the automatic external defibrillator in their equipment attended a training in how to use this device. The aim of this thesis is to determine whether the concept of the training courses is sufficient. If the theoretical part is well understandable for the respondents, and whether the practical training is sufficient - not only the actual compressions and ventilation, but also the use of an automatic external defibrillator, or whether it would be appropriate to extend this training. In this research I used a quantitative method - an...

There is a growing consensus that life-threatening cardiac arrhythmias like ven- tricular tachycardia (VT) or ventricular fibrillation (VF) arise because of the formation of spiral waves of electrical activation in cardiac tissue; unbroken spiral waves are associated with VT and broken ones with VF. Several experimental studies have shown that in homogeneities in cardiac tissue can have dramatic effects on such spiral waves. In this thesis we focus on spiral-wave dynamics in mathematical models of human ventricular tissue which contain (a) conduction in homogeneities, (b) ionic in- homogeneities, (c) fibroblasts, (d) Purkinje fibers. We also study the effect of a periodic deformation of the simulation domain on spiral wave-dynamics. Chapter 2 contains our study of “Spiral-Wave Dynamics and Its Control in the Presence of In homogeneities in Two Mathematical Models for Human Cardiac Tissue”; this chapter follows closely parts of a paper we have published [1]. Chapter 3 contains our study of “Spiral-wave dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Fibroblasts”; this chapter follows closely a paper that we have submitted for publication. Chapter 4 contains our study of “Spiral-wave Dynamics in Ionically Realistic Mathematical Models for Human Ventricular Tis- sue: The Effects of Periodic Deformation”; this chapter follows closely a paper that we have submitted for publication. Chapter 5 contains our study of “Spiral-wave dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Purkinje fibers”; this chapter follows closely a paper that we will submit for publication soon. In chapter 2, we study systematically the AP morphology in a state-of-the-art mathematical model of human ventricular tissue due to ten-Tusscher, Noble, Noble, and Panfilov (the TNNP04 model); we also look at the contribution of individual ionic currents to the AP by partially or completely blocking ion channels associated with the ionic currents. We then carry out systematic studies of plane- wave and circular-wave dynamics in the TNNP04 model for cardiac tissue model. We present a detailed and systematic study of spiral-wave turbulence and spa- tiotemporal chaos in two mathematical models for human cardiac tissue due to (a) ten-Tusscher and Panfilov (the TP06 model) and (b) ten-Tusscher, Noble, Noble, and Panfilov (the TNNP04 model). In particular, we use extensive numerical simulations to elucidate the interaction of spiral waves in these models with conduction and ionic in homogeneities. Our central qualitative result is that, in all these models, the dynamics of such spiral waves depends very sensitively on such in homogeneities. A major goal here is to develop low amplitude defibrillation schemes for the elimination of VT and VF, especially in the presence of in homogeneities that occur commonly in cardiac tissue. Therefore, we study a control scheme that has been suggested for the control of spiral turbulence, via low-amplitude current pulses, in such mathematical models for cardiac tissue; our investigations here are designed to examine the efficacy of such control scheme in the presence of in homogeneities in biophysical realistic models. We find that a scheme that uses control pulses on a spatially extended mesh is more successful in the elimination of spiral turbulence than other control schemes. We discuss the theoretical and experimental implications of our study that have a direct bearing on defibrillation, the control of life-threatening cardiac arrhythmias such as ventricular fibrillation. In chapter 3, we study the role of cardiac fibroblasts in ventricular tissue; we use the TNNP04 model for the myocyte cell, and the fibroblasts are modelled as passive cells. Cardiac fibroblasts, when coupled functionally with myocytes, can modulate their electrophysiological properties at both cellular and tissue levels. Therefore, it is important to study the effects of such fibroblasts when they are coupled with myocytes. Chapter 3 contains our detailed and systematic study of spiral-wave dynamics in the presence of fibroblasts in both homogeneous and inhomogeneous domains of the TNNP04 model for cardiac tissue. We carry out extensive numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for no, one-way, or two-way MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as Ef , the fibroblast resting membrane potential, the fibroblast conductance Gf , and the MF gap-junctional coupling Ggap. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as Ggap, Gf , and Ef , and (c) intercellular couplings that can be no, one-way, and two-way connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity CV decreases as a function of Ggap, for no and one-way couplings; however, for two-sided coupling, CV decreases initially and then increases as a function of Ggap, and, eventually, we observe that conduction failure occurs for low values of Ggap. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling Ggap or Ef . Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities. In chapter 4, we carry out a detailed, systematic study of spiral-wave dynamics in the presence of periodic deformation (PD) in two state-of-the-art mathematical models of human ventricular tissue, namely, the TNNP04 model and the TP06 model. To the best of our knowledge, our work is the first, systematic study of the dynamics of spiral waves of electrical activation and their transitions, in the presence of PD, in such biophysically realistic mathematical models of cardiac tissue. In our studies, we use three types of initial conditions whose time evolutions lead to the following states in the absence of PD: (a) a single rotating spiral (RS), (b) a spiral-turbulence (ST) state, with a single meandering spiral, and (c) an ST state with multiple broken spirals for both these models. We then show that the imposition of PD in these three cases leads to a rich variety of spatiotemporal pat- terns in the transmembrane potential including states with (a) an RS state with n-cycle temporal evolution (here n is a positive integer), (b) rotating-spiral states with quasiperiodic (QP) temporal evolution, (c) a state with a single meandering spiral MS, which displays spatiotemporal chaos, (d) an ST state, with multiple bro- ken spirals, and (e) a quiescent state in which all spirals are absorbed (SA). For all three initial conditions, precisely which one of the states is obtained depends on the amplitudes and the frequencies of the PD in the x and y directions. We also suggest specific experiments that can test the results of our simulations. We also study, in the presence of PD, the efficacy of a low-amplitude control scheme that has been suggested, hitherto only without PD, for the control of spiral-wave turbulence, via low-amplitude current pulses applied on a square mesh, in mathematical models for cardiac tissue. We also develop line-mesh and rectangular-mesh variants of this control scheme. We find that square- and line-mesh-based, low-amplitude control schemes suppress spiral-wave turbulence in both the TP06 and TNNP04 models in the absence of PD; however, we show that the line-based scheme works with PD only if the PD is applied along one spatial direction. We then demonstrate that a minor modification of our line-based control scheme can suppress spiral-wave turbulence: in particular, we introduce a rectangular-mesh-based control scheme, in which we add a few control lines perpendicular to the parallel lines of the line- based control scheme; this rectangular-mesh scheme is a significant improvement over the square-mesh scheme because it uses fewer control lines than the one based on a square mesh. In chapter 5, we have carried out detailed numerical studies of (a) a single unit of an endocardial cell and Purkinje cell (EP) composite and (b) a two-dimensional bilayer, which contains such EP composites at each site. We have considered bio- physically realistic ionic models for human endocardial cells (Ecells) and Purkinje cells (Pcells) to model EP composites. Our study has been designed to elucidate the sensitive dependence, on parameters and initial conditions, of (a) the dynamics of EP composites and (b) the spatiotemporal evolution of spiral waves of electrical activation in EP-bilayer domains. We examine this dependence on myocyte parameters by using the three different parameter sets P1, P2, and P3; to elucidate the initial-condition dependence we vary the time at which we apply the S2 pulse in our S1-S2 protocol; we also investigate the dependence of the spatiotemporal dynamics of our system on the EP coupling Dgap, and on the number of Purkinje- ventricular junctions (PVJs), which are measured here by the ratio R, the ratio of the total number of sites to the number of PVJs in our simulation domain. Our studies on EP composites show that the frequency of autorhythmic activity of a P cell depends on the diffusive gap-junctional conductance Dgap. We perform a set of simulations to understand the source-sink relation between the E and P cells in an EP composite; such a source-sink relation is an important determinant of wave dynamics at the tissue level. Furthermore, we have studied the restitution properties of an isolated E cell and a composite EP unit to uncover this effect on wave dynamics in 2D, bilayers of EP composites. Autorhythmicity is an important property of Purkinje cell; it helps to carry electrical signals rapidly from bundle of His to the endocardium. Our investigation of an EP composite shows that the cycle length (CL) of autorhythmic activity decreases, compared to that of an uncoupled Purkinje cell. Furthermore, we find that the APD increases for an EP composite, compared to that of an uncoupled P cell. In our second set of simulations for an EP-composite unit, we have obtained the AP behaviors and the amount of flux that flows from the E to the P cell during the course of the AP. The direction of flow of this flux is an important quantity that identifies which one of these cells act as a source or a sink in this EP composite. We have found that the P cell in an EP composite acts as a stimulation-current source for the E cell in the depolarization phase of the AP, when the stimulus is applied to both cells or to the P cell only. However, the P cell behaves both as a source and a sink when the stimulus is applied to the E cell only. In our third set of simulations for an EP composite unit, we have calculated the restitution of the APD; this plays an important role in deciding the stability of spiral waves in mathematical models for cardiac tissue. Our simulation shows that, for the EP composite with high coupling (Dgap = Dmm~10), the APDR slope decreases, relative to its value for an isolated E cell, for parameter sets P1 and P2, and first increases (for 50 ≤ DI ≤ 100 ms) and then decreases for the parameter set P3 ; however, for low coupling (Dgap = Dmm~100), the variation of the AP D as function of DI, for an EP composite, shows biphasic behavior for all these three parameter sets. We found that the above dynamics in EP cable type domains, with EP composites, depends sensitively on R. We hope our in silico studies of spiral-wave dynamics in a variety of state-of-the- art ionic models for ventricular tissue will stimulate more experimental studies that examine such dynamics.

Introduction: Ventricular arrhythmias (VAs) are common after an acute coronary syndrome (ACS) and are associated with worse clinical outcomes. However, little is known about recent trends in their occurrence, their association with serum glucose levels, and their psychological impact in ACS setting. Methods: We examined 25-year (1986-2011) trends in the incidence rates (IRs) and hospital case-fatality rates (CFRs) of VAs, and the association between serum glucose levels and VAs in patients with an acute myocardial infarction (AMI) in the Worcester Heart Attack Study. Lastly, we examined the relationship between in-hospital occurrence of VAs and 12-month progression of depression and anxiety among hospital survivors of an ACS in the longitudinal TRACE-CORE study. Results: We found the IRs declined for several major VAs between 1986 and 2011while the hospital CFRs declined in both patients with and without VAs over this period. Elevated serum glucose levels at hospital admission were associated with a higher risk of developing in-hospital VAs. Occurrence of VAs, however, was not associated with worsening progression of symptoms of depression and/or anxiety over a 12-month follow-up period in patients discharged after an ACS. Conclusions: The burden and impact of VAs in patients with an AMI has declined over time. Elevated serum glucose levels at hospital admission may serve as a predictor for in-hospital occurrence of serious cardiac arrhythmias. In-hospital occurrence of VAs may not be associated with worsening progression of symptoms of depression and anxiety in patients with an ACS.

No description available.

The Thesis deals with the issue of provision of advanced life support in a Hospital. The main focus is the process, algorithm, of successive individual steps, its correct performance in practice should lead to the provision of effective CPR or to minimize subsequent post-resuscitation complications. The Thesis is mainly focused on non-medical health worker, as an important member of the healthcare team, his tasks, responsibilities and competences. The theoretical part will be processed according to the current guidelines of the European Resuscitation Council. Within the subsequent empirical part is included the methodology of realized research, the process of data collection, and the final interpretation of the results, followed by analysis and discussion. The survey is conducted by quantitative research, using the questionnaire survey. The aim of the research was to determine respondents' level of theoretical training, ways of continuing education and current conditions at selected workplaces. Based on detected results, the steps for nursing practice are proposed. KEY WORDS: advanced life support, sudden cardial arrest, sudden respiratory arrest, ventricular fibrillation, electrical defibrillation, algorithm of KPCR, post - resuscitation syndrome, activities of nurse.

L'arrêt cardiaque est principalement d'étiologie cardio-vasculaire. Dans le contexte actuel des arrêts cardiaques extrahospitaliers, 20 à 25% des victimes présentent une fibrillation ventriculaire. Environ 3 à 5% des personnes sont sauvées sans séquelle neurologique. La survie à un arrêt cardiaque extrahospitalier dépend d'une prise en charge précoce et rapide de la victime. Les premiers témoins actifs réalisant la réanimation cardio-pulmonaire combinée à l'utilisation d'un défibrillateur sont ainsi un maillon important pour sauver la victime.Notre objectif principal est d'améliorer le taux de survie à un arrêt cardiaque extrahospitalier. Une première voie d'investigation est de proposer un fonctionnement de défibrillateur optimal combinant judicieusement les différents modules de détection embarqués (détection de fibrillation ventriculaire, détection de massage cardiaque, détection d'interférences électromagnétiques) afin de réduire les temps de pause péri-choc durant la procédure de réanimation. En effet, pendant ces temps, dits « hands-off » en anglais, aucun geste de secours n'est administré au patient qui, lui, voit d'une part sa pression de perfusion coronarienne chuter, d'autre part la probabilité de succès des tentatives de défibrillation décroître. C'est pourquoi une deuxième voie d'investigation porte sur la prédiction de l'efficacité de choc. Dans ce contexte, nous proposons de combiner des paramètres de l'électrocardiogramme dans les domaines temporel, fréquentiel et de la dynamique non-linéaire. Un classifieur bayésien utilisant le modèle de mélange de gaussiennes a été appliqué aux vecteurs de paramètres les plus prédicteurs de l'issue de la défibrillation et l'algorithme Espérance-Maximisation a permis de mener à bien la procédure d'apprentissage des paramètres du modèle probabiliste représentant les distributions conditionnelles de classe.L'ensemble des méthodes proposées a permis d'atteindre des résultats prometteurs pour à la fois réduire les temps de pause péri-choc et prédire l'efficacité de défibrillation et ainsi espérer améliorer le taux de survie à un arrêt cardiaque / The cardiac arrest is mainly of cardiovascular etiology. In the actual context of out-of-hospital cardiac arrests, 20 to 25% of the victims present a ventricular fibrillation. About 3 to 5% of the victims are saved without neurological damage. The chance of surviving a cardiac arrest outside an hospital depends on the early and fast support of the victim. The first active witnesses performing cardiopulmonary resuscitation combined with the use of a defibrillator are an important link to save the victim.Our main objective is to improve survival rate in out-of-hospital cardiac arrest cases. A first way of investigation is to propose an optimal functioning of defibrillator combining wisely the different processes of detection embedded (ventricular fibrillation detection, chest compressions detection, electromagnetic interferences detection), in order to reduce the peri-shock pauses during the resuscitation procedure. In fact, during these pauses, known as "hands-off" pauses, no emergency action is provided to the patient, what is correlated to a drop of the coronary pression, but also to a decrease of the chance of successful defibrillation. That is the reason why, a second way of investigation is based on the prediction of the efficiency of defibrillation. In this context, we propose to use a combination of parameters extracted from electrocardiogram in time, frequency and non-linear dynamics domains. A bayesian classifier using a gaussian mixture model was applied to the vectors of parameters, which are the most predictor of the defibrillation outcome and the algorithm Expectation-Maximization allowed to learn the parameters of the probabilistic model representing the class conditional distributions.All of the proposed methods allowed to reach promising results for both reducing the peri-shock pauses and predicting the efficiency of defibrillation in hope to improve the survival rate in cardiac arrest cases

[ES] Las arritmias cardíacas son un problema importante para los sistemas de salud en el mundo desarrollado debido a su alta incidencia y prevalencia a medida que la población envejece. La fibrilación auricular (FA) y la fibrilación ventricular (FV) se encuentran entre las arritmias más complejas observadas en la práctica clínica. Las consecuencias clínicas de tales alteraciones arrítmicas incluyen el desarrollo de eventos cardioembólicos complejos en la FA, y repercusiones dramáticas debido a procesos fibrilatorios sostenidos que amenazan la vida infringiendo daño neurológico tras paro cardíaco por FV, y que pueden provocar la muerte súbita cardíaca (MSC). Sin embargo, a pesar de los avances tecnológicos de las últimas décadas, sus mecanismos intrínsecos se comprenden de forma incompleta y, hasta la fecha, las estrategias terapéuticas carecen de una base mecanicista suficiente y poseen bajas tasas de éxito. Entre los mecanismos implicados en la inducción y perpetuación de arritmias cardíacas, como la FA, se cree que las dinámicas de las fuentes focales y reentrantes de alta frecuencia, en sus diferentes modalidades, son las fuentes primarias que mantienen la arritmia. Sin embargo, se sabe poco sobre los atractores, así como, de la dinámica espacio-temporal de tales fuentes fibrilatorias primarias, específicamente, las fuentes focales o rotacionales dominantes que mantienen la arritmia. Por ello, se ha desarrollado una plataforma computacional, para comprender los factores (activos, pasivos y estructurales) determinantes, y moduladores de dicha dinámica. Esto ha permitido establecer un marco para comprender la compleja dinámica de los rotores con énfasis en sus propiedades deterministas para desarrollar herramientas basadas en los mecanismos para ayuda diagnóstica y terapéutica. Comprender los procesos fibrilatorios es clave para desarrollar marcadores y herramientas fisiológica- y clínicamente relevantes para la ayuda de diagnóstico temprano. Específicamente, las propiedades espectrales y de tiempo-frecuencia de los procesos fibrilatorios han demostrado resaltar el comportamiento determinista principal de los mecanismos intrínsecos subyacentes a las arritmias y el impacto de tales eventos arrítmicos. Esto es especialmente relevante para determinar el pronóstico temprano de los supervivientes comatosos después de un paro cardíaco debido a fibrilación ventricular (FV). Las técnicas de mapeo electrofisiológico, el mapeo eléctrico y óptico cardíaco, han demostrado ser recursos muy valiosos para dar forma a nuevas hipótesis y desarrollar nuevos enfoques mecanicistas y estrategias terapéuticas mejoradas. Esta tecnología permite además el trabajo multidisciplinar entre clínicos y bioingenieros, para el desarrollo y validación de dispositivos y metodologías para identificar biomarcadores multi-dominio que permitan rastrear con precisión la dinámica de las arritmias identificando fuentes dominantes y atractores con alta precisión para ser dianas de estrategias terapeúticas innovadoras. Es por ello que uno de los objetivos fundamentales ha sido la implantación y validación de nuevos sistemas de mapeo en distintas configuraciones que sirvan de plataforma de desarrollo de nuevas estrategias terapeúticas. Aunque el mapeo panorámico es el método principal y más completo para rastrear simultáneamente biomarcadores electrofisiológicos, su adopción por la comunidad científica es limitada principalmente debido al coste elevado de la tecnología. Aprovechando los avances tecnológicos recientes, nos hemos enfocado en desarrollar, y validar, sistemas de mapeo óptico de alta resolución para registro panorámico cardíaco, utilizando modelos clínicamente relevantes para la investigación básica y la bioingeniería. / [CAT] Les arítmies cardíaques són un problema important per als sistemes de salut del món desenvolupat a causa de la seva alta incidència i prevalença a mesura que la població envelleix. La fibril·lació auricular (FA) i la fibril·lació ventricular (FV), es troben entre les arítmies més complexes observades a la pràctica clínica. Les conseqüències clíniques d'aquests trastorns arítmics inclouen el desenvolupament d'esdeveniments cardioembòlics complexos en FA i repercussions dramàtiques a causa de processos fibril·latoris sostinguts que posen en perill la vida amb danys neurològics posteriors a la FV, que condueixen a una aturada cardíaca i a la mort cardíaca sobtada (SCD). Tanmateix, malgrat els avanços tecnològics de les darreres dècades, els seus mecanismes intrínsecs s'entenen de forma incompleta i, fins a la data, les estratègies terapèutiques no tenen una base mecanicista suficient i tenen baixes taxes d'èxit. La majoria dels avenços en el desenvolupament de biomarcadors òptims i noves estratègies terapèutiques en aquest camp provenen de tècniques valuoses en la investigació de mecanismes d'arítmia. Entre els mecanismes implicats en la inducció i perpetuació de les arítmies cardíaques, es creu que les fonts primàries subjacents a l'arítmia són les fonts focals reingressants d'alta freqüència dinàmica i AF, en les seves diferents modalitats. Tot i això, se sap poc sobre els atractors i la dinàmica espaciotemporal d'aquestes fonts primàries fibril·ladores, específicament les fonts rotacionals o focals dominants que mantenen l'arítmia. Per tant, s'ha desenvolupat una plataforma computacional per entendre determinants actius, passius, estructurals i moduladors d'aquestes dinàmiques. Això va permetre establir un marc per entendre la complexa dinàmica multidomini dels rotors amb ènfasi en les seves propietats deterministes per desenvolupar enfocaments mecanicistes per a l'ajuda i la teràpia diagnòstiques. La comprensió dels processos fibril·latoris és clau per desenvolupar puntuacions i eines rellevants fisiològicament i clínicament per ajudar al diagnòstic precoç. Concretament, les propietats espectrals i de temps-freqüència dels processos fibril·latoris han demostrat destacar un comportament determinista important dels mecanismes intrínsecs subjacents a les arítmies i l'impacte d'aquests esdeveniments arítmics. Mitjançant coneixements previs, processament de senyals, tècniques d'aprenentatge automàtic i anàlisi de dades, es va desenvolupar una puntuació de risc mecanicista a la aturada cardíaca per FV. Les tècniques de cartografia òptica cardíaca i electrofisiològica han demostrat ser recursos inestimables per donar forma a noves hipòtesis i desenvolupar nous enfocaments mecanicistes i estratègies terapèutiques. Aquesta tecnologia ha permès durant molts anys provar noves estratègies terapèutiques farmacològiques o ablatives i desenvolupar mètodes multidominis per fer un seguiment precís de la dinàmica d'arrímies que identifica fonts i atractors dominants. Tot i que el mapatge panoràmic és el mètode principal per al seguiment simultani de paràmetres electrofisiològics, la seva adopció per part de la comunitat multidisciplinària d'investigació cardiovascular està limitada principalment pel cost de la tecnologia. Aprofitant els avenços tecnològics recents, ens centrem en el desenvolupament i la validació de sistemes de mapes òptics de baix cost per a imatges panoràmiques mitjançant models clínicament rellevants per a la investigació bàsica i la bioenginyeria. / [EN] Cardiac arrhythmias are a major problem for health systems in the developed world due to their high incidence and prevalence as the population ages. Atrial fibrillation (AF) and ventricular fibrillation (VF), are amongst the most complex arrhythmias seen in the clinical practice. Clinical consequences of such arrhythmic disturbances include developing complex cardio-embolic events in AF, and dramatic repercussions due to sustained life-threatening fibrillatory processes with subsequent neurological damage under VF, leading to cardiac arrest and sudden cardiac death (SCD). However, despite the technological advances in the last decades, their intrinsic mechanisms are incompletely understood, and, to date, therapeutic strategies lack of sufficient mechanistic basis and have low success rates. Most of the progress for developing optimal biomarkers and novel therapeutic strategies in this field has come from valuable techniques in the research of arrhythmia mechanisms. Amongst the mechanisms involved in the induction and perpetuation of cardiac arrhythmias such AF, dynamic high-frequency re-entrant and focal sources, in its different modalities, are thought to be the primary sources underlying the arrhythmia. However, little is known about the attractors and spatiotemporal dynamics of such fibrillatory primary sources, specifically dominant rotational or focal sources maintaining the arrhythmia. Therefore, a computational platform for understanding active, passive and structural determinants, and modulators of such dynamics was developed. This allowed stablishing a framework for understanding the complex multidomain dynamics of rotors with enphasis in their deterministic properties to develop mechanistic approaches for diagnostic aid and therapy. Understanding fibrillatory processes is key to develop physiologically and clinically relevant scores and tools for early diagnostic aid. Specifically, spectral and time-frequency properties of fibrillatory processes have shown to highlight major deterministic behaviour of intrinsic mechanisms underlying the arrhythmias and the impact of such arrhythmic events. Using prior knowledge, signal processing, machine learning techniques and data analytics, we aimed at developing a reliable mechanistic risk-score for comatose survivors of cardiac arrest due to VF. Cardiac optical mapping and electrophysiological mapping techniques have shown to be unvaluable resources to shape new hypotheses and develop novel mechanistic approaches and therapeutic strategies. This technology has allowed for many years testing new pharmacological or ablative therapeutic strategies, and developing multidomain methods to accurately track arrhymia dynamics identigying dominant sources and attractors. Even though, panoramic mapping is the primary method for simultaneously tracking electrophysiological parameters, its adoption by the multidisciplinary cardiovascular research community is limited mainly due to the cost of the technology. Taking advantage of recent technological advances, we focus on developing and validating low-cost optical mapping systems for panoramic imaging using clinically relevant models for basic research and bioengineering. / Calvo Saiz, CJ. (2022). Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182329 / TESIS