Computer-Assisted Electroanatomical Guidance for Cardiac Electrophysiology Procedures

Cardiac arrhythmias are serious life-threatening episodes affecting both the aging population and younger patients with pre-existing heart conditions. One of the most effective therapeutic procedures is the minimally-invasive catheter-driven endovascular electrophysiology study, whereby electrical potentials and activation patterns in the affected cardiac chambers are measured and subsequent ablation of arrhythmogenic tissue is performed. Despite emerging technologies such as electroanatomical mapping and remote intraoperative navigation systems for improved catheter manipulation and stability, successful ablation of arrhythmias is still highly-dependent on the operator’s skills and experience. This thesis proposes a framework towards standardisation in the electroanatomical mapping and ablation planning by merging knowledge transfer from previous cases and patient-specific data. In particular, contributions towards four different procedural aspects were made: optimal electroanatomical mapping, arrhythmia path computation, catheter tip stability analysis, and ablation simulation and optimisation. In order to improve the intraoperative electroanatomical map, anatomical areas of high mapping interest were proposed, as learned from previous electrophysiology studies. Subsequently, the arrhythmic wave propagation on the endocardial surface and potential ablation points were computed. The ablation planning is further enhanced, firstly by the analysis of the catheter tip stability and the probability of slippage at sparse locations on the endocardium and, secondly, by the simulation of the ablation result from the computation of convolutional matrices which model mathematically the ablation process. The methods proposed by this thesis were validated on data from patients with complex congenital heart disease, who present unusual cardiac anatomy and consequently atypical arrhythmias. The proposed methods also build a generic framework for computer guidance of electrophysiology, with results showing complementary information that can be easily integrated into the clinical workflow.Open Acces

Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the leading cause of ischemic stroke and is the most commonly observed arrhythmia in clinical cardiology. Catheter ablation of AF, in which specific regions of cardiac anatomy associated with AF are intenionally injured to create scar tissue, has been honed over the last 15 years to become a relatively common and safe treatment option. However, the success of these anatomically driven ablation strategies, particularly in hearts that have been exposed to AF for extended periods, remains poor. AF induces changes in the electrical and structural properties of the cardiac tissue that further promotes the permanence of AF. In a process known as electroanatomical (EAM) mapping, clinicians record time signals known as electrograms (EGMs) from the heart and the locations of the recording sites to create geometric representations, or maps, of the electrophysiological properties of the heart. Analysis of the maps and the individual EGM morphologies can indicate regions of abnormal tissue, or substrates that facilitate arrhythmogenesis and AF perpetuation. Despite this progress, limitations in the control of devices currently used for EAM acquisition and reliance on suboptimal metrics of tissue viability appear to be hindering the potential of treatment guided by substrate mapping. In this research, we used computational models of cardiac excitation to evaluate param- eters of EAM that affect the performance of substrate mapping. These models, which have been validated with experimental and clinical studies, have yielded new insights into the limitations of current mapping systems, but more importantly, they guided us to develop new systems and metrics for robust substrate mapping. We report here on the progress in these simulation studies and on novel measurement approaches that have the potential to improve the robustness and precision of EAM in patients with arrhythmias. Appropriate detection of proarrhythmic substrates promises to improve ablation of AF beyond rudimentary destruction of anatomical targets to directed targeting of complicit tissues. Targeted treatment of AF sustaining tissues, based on the substrate mapping approaches described in this dissertation, has the potential to improve upon the efficacy of current AF treatment options

Sensitivity and specificity of substrate mapping: An in silico framework for the evaluation of electroanatomical substrate mapping strategies

pre-printBackground - Voltage mapping is an important tool for characterizing proarrhythmic electrophysiological substrate, yet it is subject to geometric factors that influence bipolar amplitudes and thus compromise performance. The aim of this study was to characterize the impact of catheter orientation on the ability of bipolar amplitudes to accurately discriminate between healthy and diseased tissues. Methods and Results - We constructed a three-dimensional, in-silico, bidomain model of cardiac tissue containing transmural lesions of varying diameter. A planar excitation wave was stimulated and electrograms were sampled with a realistic catheter model at multiple positions and orientations. We carried out validation studies in animal experiments of acute ablation lesions mapped with a clinical mapping system. Bipolar electrograms sampled at higher inclination angles of the catheter with respect to the tissue demonstrated improvements in both sensitivity and specificity of lesion detection. Removing low voltage electrograms with concurrent activation of both electrodes, suggesting false attenuation of the bipolar electrogram due to alignment with the excitation wavefront, had little effect on the accuracy of voltage mapping. Conclusions - Our results demonstrate possible mechanisms for the impact of catheter orientation on voltage mapping accuracy. Moreover, results from our simulations suggest that mapping accuracy may be improved by selectively controlling the inclination of the catheter to record at higher angles with respect to the tissue

Statistical and Graph-Based Signal Processing: Fundamental Results and Application to Cardiac Electrophysiology

The goal of cardiac electrophysiology is to obtain information about the mechanism, function, and performance of the electrical activities of the heart, the identification of deviation from normal pattern and the design of treatments. Offering a better insight into cardiac arrhythmias comprehension and management, signal processing can help the physician to enhance the treatment strategies, in particular in case of atrial fibrillation (AF), a very common atrial arrhythmia which is associated to significant morbidities, such as increased risk of mortality, heart failure, and thromboembolic events. Catheter ablation of AF is a therapeutic technique which uses radiofrequency energy to destroy atrial tissue involved in the arrhythmia sustenance, typically aiming at the electrical disconnection of the of the pulmonary veins triggers. However, recurrence rate is still very high, showing that the very complex and heterogeneous nature of AF still represents a challenging problem. Leveraging the tools of non-stationary and statistical signal processing, the first part of our work has a twofold focus: firstly, we compare the performance of two different ablation technologies, based on contact force sensing or remote magnetic controlled, using signal-based criteria as surrogates for lesion assessment. Furthermore, we investigate the role of ablation parameters in lesion formation using the late-gadolinium enhanced magnetic resonance imaging. Secondly, we hypothesized that in human atria the frequency content of the bipolar signal is directly related to the local conduction velocity (CV), a key parameter characterizing the substrate abnormality and influencing atrial arrhythmias. Comparing the degree of spectral compression among signals recorded at different points of the endocardial surface in response to decreasing pacing rate, our experimental data demonstrate a significant correlation between CV and the corresponding spectral centroids. However, complex spatio-temporal propagation pattern characterizing AF spurred the need for new signals acquisition and processing methods. Multi-electrode catheters allow whole-chamber panoramic mapping of electrical activity but produce an amount of data which need to be preprocessed and analyzed to provide clinically relevant support to the physician. Graph signal processing has shown its potential on a variety of applications involving high-dimensional data on irregular domains and complex network. Nevertheless, though state-of-the-art graph-based methods have been successful for many tasks, so far they predominantly ignore the time-dimension of data. To address this shortcoming, in the second part of this dissertation, we put forth a Time-Vertex Signal Processing Framework, as a particular case of the multi-dimensional graph signal processing. Linking together the time-domain signal processing techniques with the tools of GSP, the Time-Vertex Signal Processing facilitates the analysis of graph structured data which also evolve in time. We motivate our framework leveraging the notion of partial differential equations on graphs. We introduce joint operators, such as time-vertex localization and we present a novel approach to significantly improve the accuracy of fast joint filtering. We also illustrate how to build time-vertex dictionaries, providing conditions for efficient invertibility and examples of constructions. The experimental results on a variety of datasets suggest that the proposed tools can bring significant benefits in various signal processing and learning tasks involving time-series on graphs. We close the gap between the two parts illustrating the application of graph and time-vertex signal processing to the challenging case of multi-channels intracardiac signals

High-Density Mapping Analysis of Electrical Spatiotemporal Behaviour in Atrial Fibrillation

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), 2022, Universidade de Lisboa, Faculdade de CiênciasDoenças cardiovasculares, tais como arritmias, são a principal causa de morte no mundo, especialmente no Sul e no Este da Ásia, e nos Estados Unidos da América [1]. As arritmas são caracterizadas pela alteração no ritmo sinusal normal do coração. Em particular, a fibrilhação auricular (FA) é a arritmia cardíaca mais comum na prática clínica, contribuindo para mais de 200 mil mortes globalmente em 2017 [2]. Caracteriza-se pela contração rápida e dessincronizada das aurículas, e está associada ao aumento da mortalidade e afecta de forma negativa a qualidade de vida dos pacientes. A FA é geralmente tratada através de medicação, porém quando esta falha, a ablação por cateter é indicada, sendo um tratamento de referência para combater esta patologia. A ablação apresenta uma taxa de sucesso de aproximadamente 50% no primeiro procedimento, sendo necessário efectuar vários procedimentos para aumentar a eficácia do tratamento [3]. A detecção desta patologia envolve, numa primeira fase, a realização de um electrocardiograma (ECG) e, posteriormente um estudo electrofisiológico para saber com precisão onde se localiza e o mecanismo subjacente à mesma. Este último implica o registo da actividade eléctrica através de electrogramas (EGM) locais em diferentes pontos das aurículas e dos ventrículos, com o auxílio de sistemas de mapeamento tridimensionais (3D) electroanatómicos, sendo um procedimento invasivo. Existem diversos métodos lineares e não lineares que permitem a análise dos EGMs nos domínios do tempo, frequência, fase, entre outros, com a finalidade de melhor compreender os mecanismos subjacentes à FA e, consequentemente aumentar a taxa de sucesso do processo de ablação e melhorar a sua eficiência. Esta área de estudo progrediu significativamente, tanto a nível de hardware, como de software. Apesar disso, os métodos desenvolvidos não têm nem acrescentado benefícios adicionais, nem melhorado significativamente a taxa de sucesso do processo de ablação. Existem várias razões para tal, e grande parte deve-se ao facto destes métodos de análise estarem incorporados nos sistemas de mapeamento e o seu software ser exclusivo. Isto leva a que não consigamos perceber como é que os algoritmos funcionam nos diferentes sistemas de mapeamento para comparar as suas diferenças e semelhanças. Devido a estes constrangimentos, os investigadores são compelidos a desenvolver os seus próprios métodos de análise e técnicas de mapeamento, o que leva à existência de uma multitude de métodos e técnicas de mapeamento que parecem ser diferentes entre si, resultando em informação ambígua e conflituosa no que diz respeito aos mecanismos da FA, e a conclusões distintas entre estudos. O sucesso do tratamento poderia aumentar se tivéssemos uma melhor compreensão dos métodos de análise e da sua aplicação no contexto da FA; perceber se os métodos apontam para o mesmo fenómeno de fibrilhação, se existe alguma correlação entre os métodos, e se a informação fornecida pelos mesmos é complementar ou redundante. Assim, o objectivo deste trabalho consistiu em implementar diferentes métodos para analisar os EGMs e a estrutura 3D da aurícula esquerda (AE) de doentes com FA, numa tentativa de responder às questões que motivaram a realização deste projecto. Em última análise, ao observar os mapas 3D da AE tendo uma melhor compreensão dos métodos, poderemos identificar com precisão as regiões na AE responsáveis por iniciar a FA, e ter mais conhecimento sobre os mecanismos responsáveis pela mesma. Desta forma, o processo de ablação poderá alcançar o seu potencial. Para este projecto, foram incluídos os mapas 3D electroanatómicos da AE de dez doentes com FA paroxística ou persistente do hospital de Santa Marta, recolhidos com o sistema de mapeamento CARTO 3. Cada ponto electroanatómico dos mapas inclui as 12 derivações do ECG, e os EGMs unipolares e bipolares registados com o cateter de mapeamento Pentaray de 20 pólos. Porém, apenas os EGMs bipolares foram incluídos na análise. Processaram-se os sinais bipolares e, devido a algumas limitações, foi possível apenas a implementação de dois métodos diferentes para os analisar: um no domínio da frequência – Frequência Dominante (FD) –, e outro no domínio da Teoria da Informação – a entropia de Shannon. De seguida, criaram-se três tipos de mapas 3D electroanatómicos da AE para cada doente: um de voltagem, cuja informação foi adquirida com o sistema de mapeamento, um de FD, e outro de entropia. A informação de cada mapa estava organizada segundo um padrão de cores. Observando os diferentes tipos de mapas da AE paralelamente, foi possível comparar os métodos, e perceber que tipo de informação cada um deles fornecia, numa tentativa de melhor compreender os mecanismos da FA. Foi possível observar em algumas regiões da AE, principalmente nos mapas de voltagem e de FD, a presença de “centros de activação” ou “centros de fibrilhação”, que poderão ser os gatilhos responsáveis por desencadear ou manter o mecanismo de fibrilhação. Para confirmar se de facto aquelas regiões eram os gatilhos de fibrilhação, seria necessário submeter os doentes ao processo de ablação e queimar essas zonas; e posteriormente acompanhar os doentes para observar os efeitos do procedimento e confirmar a hipótese. Contudo, dadas as limitações do trabalho e o facto desta área de investigação ser pouco explorada, é fulcral obter um maior número de estudo comparativos entre mais métodos de diferentes domínios e confirmar se apontam ou não para o mesmo fenómeno de fibrilhação. Apesar de terem sido implementados apenas dois métodos de análise dos EGMs, o projecto permitiu a comparação entre os mesmos, uma área de estudo por onde ainda há muito para investigar. Com mais conhecimento sobre os diferentes métodos, a sua aplicação, inter-relação e adequação no estudo dos mecanismos da FA e das propriedades electrofisiológicas desta patologia, é possível desenvolver procedimentos de ablação mais eficientes e selectivos, de forma a diminuir os riscos e aumentar a taxa de sucesso do tratamento.Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice and is described by rapid and irregular contractions of the atria. Despite catheter ablation (CA) being a well-established treatment for AF, it is sub-optimal, with a success rate of approximately 50 % after a single procedure, with some patients requiring multiple procedures to achieve long-term freedom from this pathology. This prompted the proposal and development of various quantitative electrogram (EGM)-based methods along with different mapping systems with their respective mapping techniques, to better understand the mechanisms responsible for initiating and maintaining AF, thus improving ablation outcomes. However, this diversification of methods and tools resulted in disperse and inconsistent data regarding the mechanisms of AF. This work consisted of employing two different methods to analyse the electrograms (EGM): dominant frequency (DF) and Shannon entropy (ShEn). From these EGMs, metrics were then extracted and displayed in colour-coded fashion on a 3D mesh of the left atrium (LA) from patients with paroxysmal or persistent AF. The two methods were compared to understand whether or not these indicated different phenomena/mechanisms, and if these could locate sites suspected of triggering and maintaining AF. The results, while not fully conforming to the literature, allowed the comparison between different EGM analysis methods, a field of study that requires further research. Overall, this project highlighted the limited data available within the topic, hindering our understanding of AF mechanisms and development of more effective and selective ablation procedures to avoid unnecessary complications, and ultimately improve the effects of the treatment's outcomes

Multichannel Intracardiac Electrogram Analysis to Estimate the Depolarisation Wavefront Propagation: Supporting Diagnostics and Treatment of Atrial Fibrillation

Kardiale Arrhythmien sind Störungen des Herzrhythmus, welche von unregelmäßigem Herzschlag kommen. Vorhofflimmern ist die am weitesten verbreitete Herzrhythmusstörung und ist mit zunehmendem Alter weiter verbreitet. Thromboembolische Ereignisse und Störungen der Hämodynamik können als Begleiterscheinungen von Vorhofflimmern (AFib) auftreten und eine signifikant gesteigerte Morbidität und Mortalität zur Folge haben. Die Be- handlung von AFib erfolgt mit Medikamenten und zudem mit Hilfe der Katheterablation. Im Zuge der Ablation versuchen Ärzte die Bereiche arrhythmogenen Substrats zu lokalisieren. Danach werden kleine Ablationsnarben im Herzgewebe erzeugt, welche die Ausbreitung abnormaler elektrischer Erregungen im Herzen unterdrücken sollen. Die Erfolgsraten dieser Prozedur erreichen bis zu 70% nach zwei oder drei Ablationen. Im Zuge diese Arbeiten wurden die Regionen arrhythmogenen Substrats lokalisiert, und die Details der Erregungsausbreitung über dieses Substrat wurden bestimmt. Im Verlauf dieser Arbeit wurden klinische Daten, experimentelle Daten und Simulationen für die Analyse genutzt. Simulationen wurden genutzt um die lokale Aktivierungszeit (LAT) auf klinischen Anatomien zu bestimmen. Experimentelle Daten wurden mit Hilfe eines Elektrodenpatches von einem Hund herzen erfasst. Klinische Daten wurden mit Hilfe eines elektroanatomischen Mappingsystems im Rahmen klinischer Routineuntersuchungen aufgezeichnet. Die aufgezeichneten Daten wurden einer Vorverarbeitung unterzogen um messtechnische und geometrische Artefakte wie das ventrikuläre Fernfeld (VFF) oder hoch- und niederfrequentes Rauschen zu unterdrücken. Eine Vielzahl von Merkmalen wurden aus den vorbearbeiteten Daten gewonnen. Dies waren die Bestimmung des Stimulationsprokotolls, die Abschätzung der Dauer der fraktionierten Aktivität, die Korrelation der Morphologie, Spitzen-zu-Spitzen Amplitude, Bestimmung der QRS Komplexe, lokale Aktivierungszeit, die Bestimmung einer stabilen Katheterposition und die Markierung der Region des arrhythmogenen Substrats. Die Methode zur Bestimmung von Richtung und Geschwindigkeit der Erregungsausbreitung wurde bestimmt. Ein grafisches Nutzerinterface (GUI) wurde entwickelt zur Bestimmung der Ausbreitungsgeschwindigkeit und darauf basierender regionaler Analyse. Simulierte Daten wurden genutzt um die Leistungsfähigkeit der entwickelten Algorithmen zu beurteilen. Zur Simulation der LAT auf klinischen Anatomien wurde die fast marching Methode (FaMaS) genutzt. In diesen Simulationen war die goldene Wahrheit für eine Beurteilung der Parameterabschätzung bekannt. Ein umsichtiger und erfolgreicher Versuch wurde unternommen, um Muster und Geschwindig- keit der Erregungsausbreitung auf dem Vorhof zu bestimmen. Dies wurde auf Basis der LAT Zeit und stabiler Katheterpositionen durchgeführt. Interessante Regionen wurden zudem als wahrscheinliche Regionen eines arrhythmogenen Substrats im linken Vorhof markiert. Dies wurde auf Grundlage mehr als eines Merkmals und visueller Beurteilung deren Verteilung im Vorhof durchgeführt. Für die stimulierten Daten wurde die Aktivität der S1 und S2 Erregung verglichen um Änderungen in der Erregungsausbreitung abzuschätzen. Die Auswertung der experimentellen Daten wurde in Kooperation mit internationalen Part- nern aus den USA durchgeführt. Für verschiedene Szenarien wurden dabei Richtung und Muster der Erregungsausbreitung abgeschätzt. Die zeitliche und räumliche Informationen der vorgeschlagenen Method war dabei genau kontrolliert. Mit den Auswertemethoden aus dieser Arbeit können die wahrscheinliche Region des arrhythmogenen Substrats und der Verlauf der Erregungsausbreitung auf dem Vorhof für Vorhofflimmern und Vorhofflattern bestimmt werden. Diese können dem behandelnden Arzt bei der Planung der Ablationstherapie und erfolgreicher Durchführung helfen

Computational modelling of the human heart and multiscale simulation of its electrophysiological activity aimed at the treatment of cardiac arrhythmias related to ischaemia and Infarction

[ES] Las enfermedades cardiovasculares constituyen la principal causa de morbilidad y mortalidad a nivel mundial, causando en torno a 18 millones de muertes cada año. De entre ellas, la más común es la enfermedad isquémica cardíaca, habitualmente denominada como infarto de miocardio (IM). Tras superar un IM, un considerable número de pacientes desarrollan taquicardias ventriculares (TV) potencialmente mortales durante la fase crónica del IM, es decir, semanas, meses o incluso años después la fase aguda inicial. Este tipo concreto de TV normalmente se origina por una reentrada a través de canales de conducción (CC), filamentos de miocardio superviviente que atraviesan la cicatriz del infarto fibrosa y no conductora. Cuando los fármacos anti-arrítmicos resultan incapaces de evitar episodios recurrentes de TV, la ablación por radiofrecuencia (ARF), un procedimiento mínimamente invasivo realizado mediante cateterismo en el laboratorio de electrofisiología (EF), se usa habitualmente para interrumpir de manera permanente la propagación eléctrica a través de los CCs responsables de la TV. Sin embargo, además de ser invasivo, arriesgado y requerir mucho tiempo, en casos de TVs relacionadas con IM crónico, hasta un 50% de los pacientes continúa padeciendo episodios recurrentes de TV tras el procedimiento de ARF. Por tanto, existe la necesidad de desarrollar nuevas estrategias pre-procedimiento para mejorar la planificación de la ARF y, de ese modo, aumentar esta tasa de éxito relativamente baja. En primer lugar, realizamos una revisión exhaustiva de la literatura referente a los modelos cardiacos 3D existentes, con el fin de obtener un profundo conocimiento de sus principales características y los métodos usados en su construcción, con especial atención sobre los modelos orientados a simulación de EF cardíaca. Luego, usando datos clínicos de un paciente con historial de TV relacionada con infarto, diseñamos e implementamos una serie de estrategias y metodologías para (1) generar modelos computacionales 3D específicos de paciente de ventrículos infartados que puedan usarse para realizar simulaciones de EF cardíaca a nivel de órgano, incluyendo la cicatriz del infarto y la región circundante conocida como zona de borde (ZB); (2) construir modelos 3D de torso que permitan la obtención del ECG simulado; y (3) llevar a cabo estudios in-silico de EF personalizados y pre-procedimiento, tratando de replicar los verdaderos estudios de EF realizados en el laboratorio de EF antes de la ablación. La finalidad de estas metodologías es la de localizar los CCs en el modelo ventricular 3D para ayudar a definir los objetivos de ablación óptimos para el procedimiento de ARF. Por último, realizamos el estudio retrospectivo por simulación de un caso, en el que logramos inducir la TV reentrante relacionada con el infarto usando diferentes configuraciones de modelado para la ZB. Validamos nuestros resultados mediante la reproducción, con una precisión razonable, del ECG del paciente en TV, así como en ritmo sinusal a partir de los mapas de activación endocárdica obtenidos invasivamente mediante sistemas de mapeado electroanatómico en este último caso. Esto permitió encontrar la ubicación y analizar las características del CC responsable de la TV clínica. Cabe destacar que dicho estudio in-silico de EF podría haberse efectuado antes del procedimiento de ARF, puesto que nuestro planteamiento está completamente basado en datos clínicos no invasivos adquiridos antes de la intervención real. Estos resultados confirman la viabilidad de la realización de estudios in-silico de EF personalizados y pre-procedimiento de utilidad, así como el potencial del abordaje propuesto para llegar a ser en un futuro una herramienta de apoyo para la planificación de la ARF en casos de TVs reentrantes relacionadas con infarto. No obstante, la metodología propuesta requiere de notables mejoras y validación por medio de es[CA] Les malalties cardiovasculars constitueixen la principal causa de morbiditat i mortalitat a nivell mundial, causant entorn a 18 milions de morts cada any. De elles, la més comuna és la malaltia isquèmica cardíaca, habitualment denominada infart de miocardi (IM). Després de superar un IM, un considerable nombre de pacients desenvolupen taquicàrdies ventriculars (TV) potencialment mortals durant la fase crònica de l'IM, és a dir, setmanes, mesos i fins i tot anys després de la fase aguda inicial. Aquest tipus concret de TV normalment s'origina per una reentrada a través dels canals de conducció (CC), filaments de miocardi supervivent que travessen la cicatriu de l'infart fibrosa i no conductora. Quan els fàrmacs anti-arítmics resulten incapaços d'evitar episodis recurrents de TV, l'ablació per radiofreqüència (ARF), un procediment mínimament invasiu realitzat mitjançant cateterisme en el laboratori de electrofisiologia (EF), s'usa habitualment per a interrompre de manera permanent la propagació elèctrica a través dels CCs responsables de la TV. No obstant això, a més de ser invasiu, arriscat i requerir molt de temps, en casos de TVs relacionades amb IM crònic fins a un 50% dels pacients continua patint episodis recurrents de TV després del procediment d'ARF. Per tant, existeix la necessitat de desenvolupar noves estratègies pre-procediment per a millorar la planificació de l'ARF i, d'aquesta manera, augmentar la taxa d'èxit, que es relativament baixa. En primer lloc, realitzem una revisió exhaustiva de la literatura referent als models cardíacs 3D existents, amb la finalitat d'obtindre un profund coneixement de les seues principals característiques i els mètodes usats en la seua construcció, amb especial atenció sobre els models orientats a simulació de EF cardíaca. Posteriorment, usant dades clíniques d'un pacient amb historial de TV relacionada amb infart, dissenyem i implementem una sèrie d'estratègies i metodologies per a (1) generar models computacionals 3D específics de pacient de ventricles infartats capaços de realitzar simulacions de EF cardíaca a nivell d'òrgan, incloent la cicatriu de l'infart i la regió circumdant coneguda com a zona de vora (ZV); (2) construir models 3D de tors que permeten l'obtenció del ECG simulat; i (3) dur a terme estudis in-silico de EF personalitzats i pre-procediment, tractant de replicar els vertaders estudis de EF realitzats en el laboratori de EF abans de l'ablació. La finalitat d'aquestes metodologies és la de localitzar els CCs en el model ventricular 3D per a ajudar a definir els objectius d'ablació òptims per al procediment d'ARF. Finalment, a manera de prova de concepte, realitzem l'estudi retrospectiu per simulació d'un cas, en el qual aconseguim induir la TV reentrant relacionada amb l'infart usant diferents configuracions de modelatge per a la ZV. Validem els nostres resultats mitjançant la reproducció, amb una precisió raonable, del ECG del pacient en TV, així com en ritme sinusal a partir dels mapes d'activació endocardíac obtinguts invasivament mitjançant sistemes de mapatge electro-anatòmic en aquest últim cas. Això va permetre trobar la ubicació i analitzar les característiques del CC responsable de la TV clínica. Cal destacar que aquest estudi in-silico de EF podria haver-se efectuat abans del procediment d'ARF, ja que el nostre plantejament està completament basat en dades clíniques no invasius adquirits abans de la intervenció real. Aquests resultats confirmen la viabilitat de la realització d'estudis in-silico de EF personalitzats i pre-procediment d'utilitat, així com el potencial de l'abordatge proposat per a arribar a ser en un futur una eina de suport per a la planificació de l'ARF en casos de TVs reentrants relacionades amb infart. No obstant això, la metodologia proposada requereix de notables millores i validació per mitjà d'estudis de simulació amb grans cohorts de pacients.[EN] Cardiovascular diseases represent the main cause of morbidity and mortality worldwide, causing around 18 million deaths every year. Among these diseases, the most common one is the ischaemic heart disease, usually referred to as myocardial infarction (MI). After surviving to a MI, a considerable number of patients develop life-threatening ventricular tachycardias (VT) during the chronic stage of the MI, that is, weeks, months or even years after the initial acute phase. This particular type of VT is typically sustained by reentry through slow conducting channels (CC), which are filaments of surviving myocardium that cross the non-conducting fibrotic infarct scar. When anti-arrhythmic drugs are unable to prevent recurrent VT episodes, radiofrequency ablation (RFA), a minimally invasive procedure performed by catheterization in the electrophysiology (EP) laboratory, is commonly used to interrupt the electrical conduction through the CCs responsible for the VT permanently. However, besides being invasive, risky and time-consuming, in the cases of VTs related to chronic MI, up to 50% of patients continue suffering from recurrent VT episodes after the RFA procedure. Therefore, there exists a need to develop novel pre-procedural strategies to improve RFA planning and, thereby, increase this relatively low success rate. First, we conducted an exhaustive review of the literature associated with the existing 3D cardiac models in order to gain a deep knowledge about their main features and the methods used for their construction, with special focus on those models oriented to simulation of cardiac EP. Later, using a clinical dataset of a chronically infarcted patient with a history of infarct-related VT, we designed and implemented a number of strategies and methodologies to (1) build patient-specific 3D computational models of infarcted ventricles that can be used to perform simulations of cardiac EP at the organ level, including the infarct scar and the surrounding region known as border zone (BZ); (2) construct 3D torso models that enable to compute the simulated ECG; and (3) carry out pre-procedural personalized in-silico EP studies, trying to replicate the actual EP studies conducted in the EP laboratory prior to the ablation. The goal of these methodologies is to allow locating the CCs into the 3D ventricular model in order to help in defining the optimal ablation targets for the RFA procedure. Lastly, as a proof-of-concept, we performed a retrospective simulation case study, in which we were able to induce an infarct-related reentrant VT using different modelling configurations for the BZ. We validated our results by reproducing with a reasonable accuracy the patient's ECG during VT, as well as in sinus rhythm from the endocardial activation maps invasively recorded via electroanatomical mapping systems in this latter case. This allowed us to find the location and analyse the features of the CC responsible for the clinical VT. Importantly, such in-silico EP study might have been conducted prior to the RFA procedure, since our approach is completely based on non-invasive clinical data acquired before the real intervention. These results confirm the feasibility of performing useful pre-procedural personalized in-silico EP studies, as well as the potential of the proposed approach to become a helpful tool for RFA planning in cases of infarct-related reentrant VTs in the future. Nevertheless, the developed methodology requires further improvements and validation by means of simulation studies including large cohorts of patients.During the carrying out of this doctoral thesis, the author Alejandro Daniel López Pérez was financially supported by the Ministerio de Economía, Industria y Competitividad of Spain through the program Ayudas para contratos predoctorales para la formación de doctores, with the grant number BES-2013-064089.López Pérez, AD. (2019). Computational modelling of the human heart and multiscale simulation of its electrophysiological activity aimed at the treatment of cardiac arrhythmias related to ischaemia and Infarction [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124973TESI