An electromechanics-driven fluid dynamics model for the simulation of the whole human heart

We introduce a multiphysics and geometric multiscale computational model, suitable to describe the hemodynamics of the whole human heart, driven by a four-chamber electromechanical model. We first present a study on the calibration of the biophysically detailed RDQ20 active contraction model (Regazzoni et al., 2020) that is able to reproduce the physiological range of hemodynamic biomarkers. Then, we demonstrate that the ability of the force generation model to reproduce certain microscale mechanisms, such as the dependence of force on fiber shortening velocity, is crucial to capture the overall physiological mechanical and fluid dynamics macroscale behavior. This motivates the need for using multiscale models with high biophysical fidelity, even when the outputs of interest are relative to the macroscale. We show that the use of a high-fidelity electromechanical model, combined with a detailed calibration process, allows us to achieve a remarkable biophysical fidelity in terms of both mechanical and hemodynamic quantities. Indeed, our electromechanical-driven CFD simulations – carried out on an anatomically accurate geometry of the whole heart – provide results that match the cardiac physiology both qualitatively (in terms of flow patterns) and quantitatively (when comparing in silico results with biomarkers acquired in vivo). Moreover, we consider the pathological case of left bundle branch block, and we investigate the consequences that an electrical abnormality has on cardiac hemodynamics thanks to our multiphysics integrated model. The computational model that we propose can faithfully predict a delay and an increasing wall shear stress in the left ventricle in the pathological condition. The interaction of different physical processes in an integrated framework allows us to faithfully describe and model this pathology, by capturing and reproducing the intrinsic multiphysics nature of the human heart

Modelling mitral valvular dynamics–current trend and future directions

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state-of-the-art modelling of the mitral valve, including static and dynamics models, models with fluid-structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed

Numerical simulation of electrocardiograms for full cardiac cycles in healthy and pathological conditions

This work is dedicated to the simulation of full cycles of the electrical activity of the heart and the corresponding body surface potential. The model is based on a realistic torso and heart anatomy, including ventricles and atria. One of the specificities of our approach is to model the atria as a surface, which is the kind of data typically provided by medical imaging for thin volumes. The bidomain equations are considered in their usual formulation in the ventricles, and in a surface formulation on the atria. Two ionic models are used: the Courtemanche-Ramirez-Nattel model on the atria, and the "Minimal model for human Ventricular action potentials" (MV) by Bueno-Orovio, Cherry and Fenton in the ventricles. The heart is weakly coupled to the torso by a Robin boundary condition based on a resistor- capacitor transmission condition. Various ECGs are simulated in healthy and pathological conditions (left and right bundle branch blocks, Bachmann's bundle block, Wolff-Parkinson-White syndrome). To assess the numerical ECGs, we use several qualitative and quantitative criteria found in the medical literature. Our simulator can also be used to generate the signals measured by a vest of electrodes. This capability is illustrated at the end of the article

Three-dimensional cardiac computational modelling: methods, features and applications

[EN] The combination of computational models and biophysical simulations can help to interpret an array of experimental data and contribute to the understanding, diagnosis and treatment of complex diseases such as cardiac arrhythmias. For this reason, three-dimensional (3D) cardiac computational modelling is currently a rising field of research. The advance of medical imaging technology over the last decades has allowed the evolution from generic to patient-specific 3D cardiac models that faithfully represent the anatomy and different cardiac features of a given alive subject. Here we analyse sixty representative 3D cardiac computational models developed and published during the last fifty years, describing their information sources, features, development methods and online availability. This paper also reviews the necessary components to build a 3D computational model of the heart aimed at biophysical simulation, paying especial attention to cardiac electrophysiology (EP), and the existing approaches to incorporate those components. We assess the challenges associated to the different steps of the building process, from the processing of raw clinical or biological data to the final application, including image segmentation, inclusion of substructures and meshing among others. We briefly outline the personalisation approaches that are currently available in 3D cardiac computational modelling. Finally, we present examples of several specific applications, mainly related to cardiac EP simulation and model-based image analysis, showing the potential usefulness of 3D cardiac computational modelling into clinical environments as a tool to aid in the prevention, diagnosis and treatment of cardiac diseases.This work was partially supported by the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain (TIN2012-37546-C03-01 and TIN2011-28067) and the European Commission (European Regional Development Funds - ERDF - FEDER) and by "eTorso project" (GVA/2013-001404) from the Generalitat Valenciana (Spain). ALP is financially supported by the program "Ayudas para contratos predoctorales para la formacion de doctores" from the Ministerio de Economia y Competitividad of Spain (BES-2013-064089).López Pérez, AD.; Sebastián Aguilar, R.; Ferrero De Loma-Osorio, JM. (2015). 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Electro-mechanical whole-heart digital twins: A fully coupled multi-physics approach

Mathematical models of the human heart are evolving to become a cornerstone of precision medicine and support clinical decision making by providing a powerful tool to understand the mechanisms underlying pathophysiological conditions. In this study, we present a detailed mathematical description of a fully coupled multi-scale model of the human heart, including electrophysiology, mechanics, and a closed-loop model of circulation. State-of-the-art models based on human physiology are used to describe membrane kinetics, excitation-contraction coupling and active tension generation in the atria and the ventricles. Furthermore, we highlight ways to adapt this framework to patient specific measurements to build digital twins. The validity of the model is demonstrated through simulations on a personalized whole heart geometry based on magnetic resonance imaging data of a healthy volunteer. Additionally, the fully coupled model was employed to evaluate the effects of a typical atrial ablation scar on the cardiovascular system. With this work, we provide an adaptable multi-scale model that allows a comprehensive personalization from ion channels to the organ level enabling digital twin modeling

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

Biomechanical analysis of hypoplastic left heart syndrome and calcific aortic stenosis: a statistical and computational study

2021 Fall.Includes bibliographical references.Cardiovascular diseases are a leading cause of death in the United States. In this dissertation, a congenital heart disease (CHD) and a valvular disease are discussed. CHDs occur in ~5% of live births. Structural CHDs can be complex and difficult to treat, such as hypoplastic left heart syndrome (HLHS) in which the left ventricle is generally underdeveloped, representing ~9% of all congenital heart diseases. Calcific aortic stenosis is one of the most common valvular diseases in which valves thicken and stiffen, and in some cases nodular deposits form, limiting valve function that may result in flow regurgitation and outflow obstruction. The overarching hypothesis of this research is that patient-specific heart geometry and valve characteristics are linked to cardiovascular diseases and may play an important role in regulating hemodynamics within the heart. This hypothesis is studied through three specific aims. In specific aim 1, a computational fluid dynamics study was developed to quantify the hemodynamic characteristics within the right ventricles of healthy fetuses and fetuses with HLHS, using 4D patient-specific ultrasound scans. In these simulations, we find that the HLHS right ventricle exhibits a greater cardiac output than normal; yet, hemodynamics are relatively similar between normal and HLHS right ventricles. Overall, this study provides detailed quantitative flow patterns for HLHS, which has the potential to guide future prevention and therapeutic interventions, while more immediately providing additional functional detail to cardiologists to aid in decision making. The specific aim 2 is a comprehensive review in which we highlight underlying molecular mechanisms of acquired aortic stenosis calcification in relation to hemodynamics, complications related to the disease, diagnostic methods, and evolving treatment practices for calcific aortic stenosis and, bioprosthetic or native aortic scallop intentional laceration (BASILICA) procedure to free coronary arteries from obstruction. In specific aim 3, we use statistical trends and relationships to identify the role of patient-specific aortic valve characteristics in post-BASILICA coronary obstruction. The findings of this study shows that in addition to direct anatomical measurements of the aortic valve, the aspect ratios of the anatomical features are important in determining the cause of post-BASILICA coronary obstruction. The overall significance of this dissertation is that computational and statistical analysis of patient's specific flow hemodynamics and geometric characteristics can provide more insight into the cardiovascular disease and treatment approaches which can ultimately assist surgeons with procedural planning

A comprehensive and biophysically detailed computational model of the whole human heart electromechanics

While ventricular electromechanics is extensively studied, four-chamber heart models have only been addressed recently; most of these works however neglect atrial contraction. Indeed, as atria are characterized by a complex physiology influenced by the ventricular function, developing computational models able to capture the physiological atrial function and atrioventricular interaction is very challenging. In this paper, we propose a biophysically detailed electromechanical model of the whole human heart that considers both atrial and ventricular contraction. Our model includes: i) an anatomically accurate whole-heart geometry; ii) a comprehensive myocardial fiber architecture; iii) a biophysically detailed microscale model for the active force generation; iv) a 0D closed-loop model of the circulatory system; v) the fundamental interactions among the different core models; vi) specific constitutive laws and model parameters for each cardiac region. Concerning the numerical discretization, we propose an efficient segregated-intergrid-staggered scheme and we employ recently developed stabilization techniques that are crucial to obtain a stable formulation in a four-chamber scenario. We are able to reproduce the healthy cardiac function for all the heart chambers, in terms of pressure-volume loops, time evolution of pressures, volumes and fluxes, and three-dimensional cardiac deformation, with unprecedented matching (to the best of our knowledge) with the expected physiology. We also show the importance of considering atrial contraction, fibers-stretch-rate feedback and suitable stabilization techniques, by comparing the results obtained with and without these features in the model. The proposed model represents the state-of-the-art electromechanical model of the iHEART ERC project and is a fundamental step toward the building of physics-based digital twins of the human heart

Personalized Electromechanical Modeling of the Human Heart : Challenges and Opportunities for the Simulation of Pathophysiological Scenarios

Mathematische Modelle des menschlichen Herzens entwickeln sich zu einem Eckpfeiler der personalisierten Medizin. Sie sind ein nützliches Instrument und helfen klinischen Entscheidungsträgern die zugrundeliegenden Mechanismen von Herzkrankheiten zu erforschen und zu verstehen. Aufgrund der Komplexität des Herzens benötigen derartige Modelle allerdings eine detaillierte Beschreibung der physikalischen Prozesse, welche auf verschiedenen räumlichen und zeitlichen Skalen miteinander interagieren. Aus mathematischer Perspektive stellen vor allem die Entwicklung robuster numerischer Methoden für die Lösung des Modells in Raum und Zeit sowie die Identifizierung von Parametern aus patientenspezifischen Messungen eine Herausforderung dar. In dieser Arbeit wird ein detailliertes mathematisches Modell vorgestellt, welches ein vollgekoppeltes Multiskalenmodell des menschlichen Herzens beschreibt. Das Modell beinhaltet unter anderem die Ausbreitung des elektrischen Signals und die mechanische Verformung des Herzmuskels sowie eine Beschreibung des Herz-Kreislauf-Systems. Basierend auf dem neusten Stand der Technik wurden Modelle der Membrankinetik sowie der Entwicklung der aktiven Kraft zu einem einheitlichen Modell einer Herzmuskelzelle zusammengeführt. Dieses beschreibt die elektromechanische Kopplung in Herzmuskelzellen der Vorhöfe und der Herzkammern basierend auf der Physiologie im Menschen und wurde mit Hilfe von experimentellen Daten aus einzelnen Zellen neu parametrisiert. Um das elektromechanisch gekoppelte Modell des menschlichen Herzens lösen zu können, wurde ein gestaffeltes Lösungsverfahren entwickelt, welches auf bereits existierenden Softwarelösungen der Elektrophysiologie und Mechanik aufbaut. Das neue Modell wurde verwendet, um den Einfluss elektromechanischer Rückkopplungseffekte auf das Herz im Sinusrhythmus zu untersuchen. Die Simulationsergebnisse zeigten, dass elektromechanische Rückkopplungseffekte auf zellulärer Ebene einen wesentlichen Einfluss auf das mechanische Verhalten des Herzens haben. Dahingegen hatte die Verformung des Herzens nur einen geringen Einfluss auf den Diffusionskoeffizienten des elektrischen Signals. Um die verschiedenen Komponenten der Simulationssoftware zu verifizieren, wurden spezielle Probleme definiert, welche die wichtigsten Aspekte der Elektrophysiologie und der Mechanik abdecken. Zusätzlich wurden diese Probleme dazu verwendet, den Einfluss von räumlicher und zeitlicher Diskretisierung auf die numerische Lösung zu bewerten. Die Ergebnisse zeigten, dass Raum- und Zeitdiskretisierung vor allem für das elektrophysiologische Problem die limitierenden Faktoren sind, während die Mechanik hauptsächlich anfällig für volumenversteifende Effekte ist. Weiterhin wurde das Modell verwendet, um zu untersuchen, wie sich eine Verteilung der Faserspannung auf den gesamten Herzmuskel auf die Funktion der linken Herzkammer auswirkt. Hierzu wurde zusätzlich eine Spannung in die Normalenrichtungen der Fasern einer idealisierten linken Herzkammer angewandt. Es zeigte sich, dass insbesondere eine Spannung senkrecht zu den Faserschichten zu einer physiologischeren Kontraktion der Kammer führte. Allerdings konnten diese Ergebnisse auf einem ganzen Herzen nicht vollständig bestätigt werden. In einem zweiten Projekt wurde mit Hilfe eines Modells der linken Herzkammer untersucht, wie sich das Rotationsmuster der Kammer unter Modifikation der lokalen elektromechanischen Eigenschaften verändert. Hierzu wurden in vivo Daten elektromechanischer Parameter von 30 Patienten mit Herzversagen und Linksschenkelblock in das Modell integriert, simuliert und ausgewertet. Die Ergebnisse konnten die klinisch aufgestellte Hypothese nicht bestätigen und es zeigte sich keine Korrelation zwischen den elektromechanischen Parametern und dem Rotationsverhalten. Die Auswirkungen von standardisierten Ablationsstrategien zur Behandlung von Vorhofflimmern in Bezug auf die kardiovaskuläre Leistung wurde in einem Modell des ganzen Herzens untersucht. Aufgrund der Narben im linken Vorhof wurde die elektrische Aktivierung und die Steifigkeit des Herzmuskels verändert. Dies führte zu einem reduzierten Auswurfvolumen, welches in direktem Zusammenhang mit dem inaktiven Gewebe steht. Abhängig von der Steifigkeit der Narben hat sich zusätzlich der Druck im linken Vorhof erhöht. Die linke Herzkammer war nur wenig beeinflusst. Zu guter Letzt wurden schrittweise pathologische Mechanismen in das Herzmodell integriert, welche in Zusammenhang mit Herzversagen stehen und in Patienten mit dilatativer Kardiomyopathie zu beobachten sind. Die Simulationen zeigten, dass vor allem zelluläre Veränderungen bezüglich der elektrophysiologischen Eigenschaften für die schlechte mechanische Aktivtät des Herzens verantwortlich sind. Weiterhin zeigte sich, dass strukturelle Veränderungen der Anatomie und die erhöhte Steifigkeit des Herzmuskels und die damit einhergehenden Anpassungen des Herz-Kreislauf-Systems nötig sind, um in vivo Messungen zu reproduzieren. In dieser Arbeit wurde eine Simulationsumgebung vorgestellt, welche die Berechnung der elektromechanischen Aktivität des Herzens und des Herz-Kreislauf-Systems ermöglicht. Die Simulationsumgebung wurde mit Hilfe von einfachen Beispielen verifiziert und unter Einbeziehung von Daten aus der Magnetresonanztomographie validiert. Zu guter Letzt wurde die Simulationsumgebung genutzt, um klinische Fragen zu beantworten, welche andernfalls im Dunkeln blieben