Download or read book Multi scale Modeling of Cardiac Arrhythmias written by Francisco Sahli and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: In the United States, almost half a million people die each year as a result of cardiac arrhythmias. These diseases comprise a number of abnormal rhythms, where the electrical activity of the heart is disturbed. Despite decades of research, the mechanisms by which arrhythmias develop remain poorly explained. One of the main challenges is that even though arrhythmias appear at the organ level, they can be triggered by sub-cellular changes, creating an inherently multi-scale problem. Computational models can bridge across scales to provide mechanistic understanding of these conditions. This thesis elaborates on the development of these models and their applicability to different types of arrhythmias. We study how different components of these models affect their response and the consequences of clinical applications. Moreover, we develop a high resolution, multi-scale model of the heart. We model from the ionic channels in the cell, to the different distributions of cell populations, to the entire heart. This tool allow us to study, for example, the development of drug-induced arrhythmias, where if specific ionic channels are blocked, arrhythmias appear spontaneously. We also apply machine learning techniques to extract knowledge and alleviate the computational cost of these high resolution models. We anticipate the newly developed models and methodologies will help to elaborate mechanistic explanations of the development of arrhythmias and elucidate new treatments.
Download or read book Multiscale Modeling of Cardiac Electrophysiology Adaptation to Atrial and Ventricular Rhythm Disorders and Pharmacological Treatment written by Mathias Wilhelms and published by KIT Scientific Publishing. This book was released on 2014-05-22 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiscale modeling of cardiac electrophysiology helps to better understand the underlying mechanisms of atrial fibrillation, acute cardiac ischemia and pharmacological treatment. For this purpose, measurement data reflecting these conditions have to be integrated into models of cardiac electrophysiology. Several methods for this model adaptation are introduced in this thesis. The resulting effects are investigated in multiscale simulations ranging from the ion channel up to the body surface.AbstractEnglisch = Multiscale modeling of cardiac electrophysiology helps to better understand the underlying mechanisms of atrial fibrillation, acute cardiac ischemia and pharmacological treatment. For this purpose, measurement data reflecting these conditions have to be integrated into models of cardiac electrophysiology. Several methods for this model adaptation are introduced in this thesis. The resulting effects are investigated in multiscale simulations ranging from the ion channel up to the body surface.
Download or read book Multiscale Modeling of Cardiac Arrhythmogenesis Beyond the Trigger Substrate Paradigm written by Michael B Liu and published by . This book was released on 2019 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: Arrhythmias and sudden cardiac death (SCD) represent a leading cause of mortality in the US and worldwide. Currently, the most effective therapy for preventing SCD is the implantable cardioverter-defibrillator (ICD). ICDs however can only terminate arrhythmias after they have already occurred and have numerous severe side effects and poor cost-effectiveness. Therefore, the ideal anti-arrhythmic strategy is the prevention of arrhythmia initiation, or arrhythmogenesis, in the first place. Unfortunately, multiple clinical trials have demonstrated that many of the currently available anti-arrhythmic drugs are not generally effective in the prevention of ventricular arrhythmias, and in some cases may even be pro-arrhythmic unintuitively causing increased mortality. Thus, improved anti-arrhythmic strategies are needed which require improved mechanistic understanding of the arrhythmogenesis process. Computational modeling is a powerful research tool, complementary to experimental and clinical studies, to study the underlying mechanisms of arrhythmias. In this dissertation, we use computer modeling and patch clamp experiments to investigate the spontaneous initiation of triggered and reentrant ventricular arrhythmias as related to delayed afterdepolarizations (DADs) and long QT syndrome (LQTS). We first describe a dynamical threshold for DAD-mediated triggered activity which is lower than the sodium channel threshold and manifests under conditions of hypokalemia and slow spontaneous calcium release. Next, we investigate the critical factors that determine DAD-mediated triggered activity formation in cardiac tissue. Thirdly, we study whether sub-threshold DADs can act as an arrhythmogenic trigger and find that DADs can generate both triggers and a reentry substrate simultaneously. And finally, we detail a novel common mechanism of arrhythmia initiation across different genotypes of LQTS called "R-from-T", which blurs the usual notions between arrhythmia trigger and substrate beyond the traditional paradigm. The mechanistic insights gained from these studies help inform the development of new arrhythmia prevention strategies.
Download or read book Multi Scale Cardiac Electrophysiology written by Kevin Patrick Vincent and published by . This book was released on 2016 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac arrhythmias are a major source of morbidity, mortality, and healthcare cost in the United States. Arrhythmias are inherently multi-scale phenomena where cellular and subcellular abnormalities result in pathological impulse propagation. The failure of clinical therapies to sufficiently prevent or terminate arrhythmias is due, in part, to a lack of understanding of the underlying mechanisms. Integrating experimental results across spatial and temporal scales using computation modeling presents an important paradigm for investigating arrhythmia mechanisms. In this dissertation, computational modeling and experimental data at the subcellular, cellular, and tissue scales are used together to gain insight in to mechanisms of arrhythmias for clinically relevant cardiac diseases. On the cellular and subcellular scale, the ability of caveolin-3 to modulate action potential duration through ion channel regulation was investigated using action potential models to interpreting ion channel data. Two examples are presented in Chapter 2. In the first example, a mouse ventricular action potential model is able to link changes in Kv4.3 channel expression to observed QT shortening from the electrocardiogram of caveolin-3-overexpressing mice. The second example parameterizes ionic currents in a human ventricular action potential model with patch clamp data from ion channels co-expressed with Long QT Syndrome causing mutations in caveolin-3. The results identify slowed calcium-dependent inactivation of the L-type calcium channel as an potentially arrhythmogenic mechanisms. Integrating the subcellular, cellular, and tissue scales for multi-scale cardiac electrophysiology modeling presents numerical, computational, and physiological challenges. Chapter 3 examines these numerical challenges and presents a new high order finite element method to potentially reduce computational expense. This multi-scale electrophysiology solver is used to investigate the behavior of electrical rotors in the human atria in Chapter 4. Specifically, discontinuities in the fiber architecture of the right atria are shown to anchor rotors. Transgenic mouse models present a unique ability investigate genome effects on the tissue scale. The final two chapters provide literature reviews aimed towards future work investigating triggered arrhythmia mechanisms. Chapter 5 reviews the mechanisms of CaMKII mediated afterdepolarization in cardiac disease. Finally, Chapter 6 provides a detailed methodological review of Langendorff perfusion and optical mapping of ex-vivo transgenic mouse hearts.
Download or read book Personalized Multi Scale Modeling of the Atria Heterogeneities Fiber Architecture Hemodialysis and Ablation Therapy written by Martin Wolfgang Krüger and published by KIT Scientific Publishing. This book was released on 2014-05-22 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book targets three fields of computational multi-scale cardiac modeling. First, advanced models of the cellular atrial electrophysiology and fiber orientation are introduced. Second, novel methods to create patient-specific models of the atria are described. Third, applications of personalized models in basic research and clinical practice are presented. The results mark an important step towards the patient-specific model-based atrial fibrillation diagnosis, understanding and treatment.
Download or read book Theoretical Modeling of Triggered Activity in Cardiac Arrhythmias written by Mingwang Zhong and published by . This book was released on 2019 with total page 223 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Cardiovascular disease is a leading cause of death in the world and accounts for annual deaths over 800,000 in the United States. Triggered activity, describing abnormal depolarizations interrupting normal action potentials or diastole, is a mechanism underlying cardiac arrhythmias. Underlying triggered activity is the early afterdepolarization (EAD) during an action potential and the delayed afterdepolarization (DAD) during diastole. This thesis aims to investigate: 1) how Ca2+ waves present in many heart diseases, such as heart failure, emerge from Ca2+ sparks, 2) why EADs occur in the long QT syndrome types 1 and 2 (LQT1 and LQT2), 3) how antiarrhythmic targets, including the small-conductance Ca2+-activated K+ (SK) current and the late sodium current, prevent EADs, and 4) how cellular triggered activity evolves into cardiac arrhythmias at the tissue level. I primarily perform the studies by using an improved physiologically multi-scale model, which incorporates spatially distributed Ca2+ release units and the bi-directional interplay between Ca2+ and membrane voltage. In addition, the studies of LQT syndromes are carried out using experimentally measured ion currents as input into the model, which turns out to be crucial to uncover the mechanisms underlying arrhythmias. Investigation of DADs reveals that strong coupling between ryanodine receptors (RyR) is critical to induce Ca2+ waves, and the low incidence of DADs in the healthy heart with strong RyR coupling is because of the low Ca2+ sensitivity of RyR. Moreover, EADs in the transgenic LQT2 rabbit model are caused by enhanced Ca2+ sensitivity of RyR, reduced Ca2+ spark refractoriness, and nonlinearity of Na+/Ca2+ exchanger as a function of Ca2+ concentration. Blocking of late sodium current in LQT2 has been shown to prevent EADs by removing a depolarizing current and reducing intracellular Na+ load. Moreover, we propose a four-state model of the SK channel, which efficiently eliminates EADs. For the transgenic LQT1 rabbits, we use an improved whole-cell model to study EAD formation. Heterogeneity of transient outward K+ current is found to be essential to explain EAD initiation in right ventricles while no EADs but prolonged action potential in left ventricles. This heterogeneity is also critical to initiating premature ventricular contractions in a one-dimensional cable consisting of LQT1 myocytes. These studies advance the current understanding of triggered activity initiation and suggest that the SK current and the late sodium current could be therapeutic targets to prevent cardiac arrhythmias."--Author's abstract.
Download or read book Personalized Multi scale Model of Cardiac Function in Patients with Dilated Cardiomyopathy written by Ali Amr and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book A Multiscale Model to Predict the Effects of Antiarrhythmic Drugs on Cardiac Rhythms written by Jonathan D. Moreno and published by . This book was released on 2012 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: A long sought, and thus far elusive, goal has been to develop drugs to manage diseases of excitability. One such disease affecting millions each year is cardiac arrhythmia, which occurs when electrical impulses in the heart become disordered. A major reason that pharmacological management of cardiac arrhythmia has failed is because there is no adequate framework currently available to predict how drugs that target cardiac ion channels, and that have intrinsically complex dynamics, will alter the emergent electrical behavior generated in the heart. In Part I of this thesis, I present a computational modeling approach, based on and validated by experimental data, that defines key measurable parameters necessary to accurately simulate the kinetics of antiarrhythmic drugs with cardiac Na + channels, and then predicts their effects on simulated human cardiac rhythms. The model forecasts the timing of specific activation sequences where clinically relevant concentrations of the antiarrhythmic drugs flecainide and lidocaine will cause, rather than prevent, arrhythmia. We then conducted experiments in rabbit hearts to validate the model predictions. Simulations in virtual human cardiac tissue suggest a "safe concentration range" for therapeutic use. In Part II of this thesis, I extend our analysis to a congenital disease of cardiac arrhythmia - the long QT3 syndrome (LQT3) - and study a particular variant, the ?KPQ mutation. I model the effects of a new drug, ranolazine, which specifically targets the mutation-induced late Na + current, on the AKPQ mutant heart, and assess antiarrhythmic efficacy by simulating pacing sequences common in these patients. The model framework presented in this thesis is the foundation for development of a high-throughput virtual drug testing system that will allow for integration of data on drug / channel interactions, more accurate prediction of treatment efficacy that is genotype specific, and prediction of drug effects on emergent dynamics in a complex excitable system.
Download or read book Multiscale Modelling of the Cardiac Specialized Conduction System written by Rafel Bodras and published by . This book was released on 2011 with total page 172 pages. Available in PDF, EPUB and Kindle. Book excerpt: Death due to lethal cardiac arrhythmias is the leading cause of mortality in Western society. Many of the fundamental mechanisms underlying the onset of arrthythmias, their maintenance and termination, still remain poorly understood. The specialized conduction (or His-Purkinje) system is fundamental to ventricular electrophysiological function and is a key player in various cardiac diseases. In recent years, computational simulation has become an important tool in im- proving our understanding ofthese mechanisms. Current state-of-the-art computational ventric- ular electrophysiology models often do not feature a detailed representation of the specialized conduction system. Ventricular models that do incorporate the specialized conduction system often use a simplified anatomical description and are commonly based on the monodomain equations, rather than the more general bidomain equations. Thus, using computational simula- tion to investigate both normal physiological function of the specialized conduction system and pathologies in which it is involved presents difficulties. This thesis develops the techniques and tools required to model the specialized conduction sys- tem at the ventricular scale. We derive one-dimensional bidomain equations that model elec- trical propagation in the system by reducing the equations associated with a three-dimensional fibre. To complement the derived equations, we develop a numerical solution scheme for the model that is efficient enough to allow ventricular simulations. The one-dimensional bido- main model allows defibrillation studies to be performed with the specialized conduction sys- tem. Secondly, we investigate the imaging and mesh generation tools required to integrate an anatomically detailed mesh of the specialized conduction system into a current state-of-the-art ventricular mesh. Using these tools, a highly detailed rabbit-specific specialized conduction system anatomical model is developed. Simulations are performed that dem~strate the re- sponse of the specialized conduction system to defibrillation strength shocks and we compare activation sequences generated using the model to experimental recordings. Finally, we investi- gate variability in the anatomy of the system. The tools and ventricular model presented in this thesis fulfil an important role in allowing the study of the e1ectrophysiological function of the specialized conduction system at the ventricular scale.
Download or read book Modeling the Heart and the Circulatory System written by Alfio Quarteroni and published by Springer. This book was released on 2015-04-24 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book comprises contributions by some of the most respected scientists in the field of mathematical modeling and numerical simulation of the human cardiocirculatory system. The contributions cover a wide range of topics, from the preprocessing of clinical data to the development of mathematical equations, their numerical solution, and both in-vivo and in-vitro validation. They discuss the flow in the systemic arterial tree and the complex electro-fluid-mechanical coupling in the human heart. Many examples of patient-specific simulations are presented. This book is addressed to all scientists interested in the mathematical modeling and numerical simulation of the human cardiocirculatory system.
Download or read book Cardiac Mapping written by Mohammad Shenasa and published by John Wiley & Sons. This book was released on 2012-10-17 with total page 968 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac Mapping is the cardiac electrophysiologist’s GPS. It will guide you to new places in the heart and help you find the old places more easily...a valuable addition to your bookshelf Douglas P. Zipes, from the Foreword. Over the course of three previous editions, this book has become the acknowledged gold standard reference on the electro-anatomical mapping of the heart. This new edition features greatly expanded coverage—the number of chapters have doubled to 80 with 40 new chapters—on leading edge science, new clinical applications and future frontiers, authored by a who’s-who of global electrophysiology. This unique text offers truly comprehensive coverage of all areas of cardiac mapping, from core scientific principals to methodological and technical considerations to the latest data that you can put to work caring for patients. In addition, the all new 4th edition adds essential content on: Mapping in experimental models of arrhythmias Mapping supraventricular and ventricular tachyarrhythmias New catheter-based techniques Also featuring a companion website with video clips illustrating essential techniques described in the text The only state-of-the-art, stand-alone text on this dynamic subject, Cardiac Mapping is an essential resource for basic scientists, clinical electrophysiologists, cardiologists and all physicians who care for patients with cardiac arrhythmias.
Download or read book Multi Scale Computational Cardiology written by Ling Xia and published by Frontiers Media SA. This book was released on 2022-03-07 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Multiscale Modelling of Rhythm Pattern and Information Generation from Genome to Physiome written by Shangbin Chen and published by Frontiers Media SA. This book was released on 2020-06-08 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Artificial Intelligence for Computational Modeling of the Heart written by Tommaso Mansi and published by Academic Press. This book was released on 2019-12 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: Artificial Intelligence for Computational Modeling of the Heart presents recent research developments towards streamlined and automatic estimation of the digital twin of a patient's heart by combining computational modeling of heart physiology and artificial intelligence. The book first introduces the major aspects of multi-scale modeling of the heart, along with the compromises needed to achieve subject-specific simulations. Reader will then learn how AI technologies can unlock robust estimations of cardiac anatomy, obtain meta-models for real-time biophysical computations, and estimate model parameters from routine clinical data. Concepts are all illustrated through concrete clinical applications. Presents recent advances in computational modeling of heart function and artificial intelligence technologies for subject-specific applications Discusses AI-based technologies for robust anatomical modeling from medical images, data-driven reduction of multi-scale cardiac models, and estimations of physiological parameters from clinical data Illustrates the technology through concrete clinical applications and discusses potential impacts and next steps needed for clinical translation
Download or read book Integrative Computational Modeling of Calcium Handling and Cardiac Arrhythmias written by Henry Sutanto and published by Henry Sutanto. This book was released on 2021-01-01 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiomyocyte calcium handling is a major determinant of excitation-contraction coupling. Alterations in one or more calcium-handling proteins may induce arrhythmias through the formation of ectopic activity, direct and indirect ion-channel regulation, and structural remodeling. Due to the complex and tight interactions between calcium and other molecules within a cardiomyocyte, it remains experimentally challenging to study the exact contributions of calcium-handling abnormalities to arrhythmogenesis. Multiscale computational studies performed in close collaboration with laboratory experiments create new opportunities to unravel the mechanisms of arrhythmogenesis. This thesis describes the roles of integrative computational modeling in unraveling the arrhythmogenic consequences of calcium-handling abnormalities.
Download or read book Electrocardiographic Imaging written by Maria S. Guillem and published by Frontiers Media SA. This book was released on 2020-04-17 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: Electrical activity in the myocardium coordinates the contraction of the heart, and its knowledge could lead to a better understanding, diagnosis, and treatment of cardiac diseases. This electrical activity generates an electromagnetic field that propagates outside the heart and reaches the human torso surface, where it can be easily measured. Classical electrocardiography aims to interpret the 12-lead electrocardiogram (ECG) to determine cardiac activity and support the diagnosis of cardiac pathologies such as arrhythmias, altered activations, and ischemia. More recently, a higher number of leads is used to reconstruct a more detailed quantitative description of the electrical activity in the heart by solving the so-called inverse problem of electrocardiography. This technique is known as ECG imaging. Today, clinical applications of ECG imaging are showing promising results in guiding a variety of electrophysiological interventions such as catheter ablation of atrial fibrillation and ventricular tachycardia. However, in order to promote the adoption of ECG imaging in the routine clinical practice, further research is required regarding more accurate mathematical methods, further scientific validation under different preclinical scenarios and a more extensive clinical validation
Download or read book Simulating Normal and Arrhythmic Dynamics From Sub Cellular to Tissue and Organ Level written by Hans Dierckx and published by Frontiers Media SA. This book was released on 2019-10-04 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt:
