Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

Gómez, Juan Francisco Cerón; Cardona, Karen; Martínez, Laura Marqués; Sáiz, Javier; Trénor, Beatriz

doi:10.1371/journal.pone.0103273

Cited by 31 publications

(36 citation statements)

References 63 publications

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“…Similarly to the results from Gomez et al, they found that intermediate fibrosis (within experimental ranges) increased vulnerability to arrhythmias [101]. These simulation results shed light into the mechanisms by which patients or animal models in moderate stages of HF are more prone to arrhythmias than patients in the end-stage of HF.…”

Section: Consequences Of Fibrosis Derived From Computational Studiessupporting

confidence: 75%

“…The vulnerability to reentry under HF conditions and several degrees of diffuse fibrosis was also assessed by considering active fibroblast interaction. The results showed that intermediate degrees of fibrosis (14% and 28%) increased the probability of reentrant arrhythmias [101]. Similarly, Nayak et al [102] focused on the influence of fibroblast features on spiral-wave control in a 2D model.…”

Section: Consequences Of Fibrosis Derived From Computational Studiesmentioning

confidence: 97%

“…They observed a non-linear influence of increased fibroblast to myocyte coupling coefficient on current density thresholds, with an initial increase of current magnitude followed by a relaxation phase down to the current magnitude threshold for the control condition with no fibrosis. In our previous works, we showed that an intermediate degree of cellular uncoupling increased the vulnerability to reentry of the failing heart and how the degree of cellular coupling could ensure conduction [101,110].…”

Section: Simulation Of Intercellular Uncouplingmentioning

confidence: 99%

“…Indeed, the electrical coupling of cardiomyocytes with fibroblasts cells alters the anisotropic action potential propagation in the human failing heart in a fashion that significantly depends on the density of fibrotic content and on the degree of intercellular coupling. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity [101].…”

Section: Reentrant Arrhythmias In Hfmentioning

confidence: 99%

“…Phase analysis was employed in Gomez et al (see Fig. 2) [101] and other studies [127,128]. These studies showed that the presence of structural heterogeneities, such as fibrosis, increased the number of phase singularities, and thus the risk of wave break [101,129].…”

Section: Reentrant Arrhythmias In Hfmentioning

confidence: 99%

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Intermittent Failure Dynamics Characterization

et al. 2012

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Heart failure constitutes a major public health problem worldwide. Affected patients experience a number of changes in the electrical function of the heart that predispose to potentially lethal cardiac arrhythmias. Due to the multitude of electrophysiological changes that may occur during heart failure, the scientific literature is complex and sometimes ambiguous, perhaps because these findings are highly dependent on the etiology, the stage of heart failure, and the experimental model used to study these changes. Nevertheless, a number of common features of failing hearts have been documented. Prolongation of the action potential (AP) involving ion channel remodeling and alterations in calcium handling have been established as the hallmark characteristics of myocytes isolated from failing hearts. Intercellular uncoupling and fibrosis are identified as major arrhythmogenic factors. Multi-scale computational simulations are a powerful tool that complements experimental and clinical research. The development of biophysically detailed computer models of single myocytes and cardiac tissues has contributed greatly to our understanding of processes underlying excitation and repolarization in the heart. The electrical, structural, and metabolic remodeling that arises in cardiac tissues during heart failure has been addressed from different computational perspectives to further understand the arrhythmogenic substrate. This review summarizes the contributions from computational modeling and simulation to predict the underlying mechanisms of heart failure phenotypes and their implications for arrhythmogenesis, ranging from the cellular level to whole-heart simulations. The main aspects of heart failure are presented in several related sections. An overview of the main electrophysiological and structural changes that have been observed experimentally in failing hearts is followed by the description and discussion of the simulation work in this field at the cellular level, and then in 2D and 3D cardiac structures. The implications for arrhythmogenesis in heart failure are also discussed including therapeutic measures, such as drug effects and cardiac resynchronization therapy. Finally, the future challenges in heart failure modeling and simulation will be discussed.

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Section: Consequences Of Fibrosis Derived From Computational Studiessupporting

confidence: 75%

Section: Consequences Of Fibrosis Derived From Computational Studiesmentioning

confidence: 97%

Section: Simulation Of Intercellular Uncouplingmentioning

confidence: 99%

Section: Reentrant Arrhythmias In Hfmentioning

confidence: 99%

Section: Reentrant Arrhythmias In Hfmentioning

confidence: 99%

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Intermittent Failure Dynamics Characterization

et al. 2012

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A dual adaptive explicit time integration algorithm for efficiently solving the cardiac monodomain equation

Mountris

Pueyo

2021

Numer Methods Biomed Eng

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The monodomain model is widely used in in‐silico cardiology to describe excitation propagation in the myocardium. Frequently, operator splitting is used to decouple the stiff reaction term and the diffusion term in the monodomain model so that they can be solved separately. Commonly, the diffusion term is solved implicitly with a large time step while the reaction term is solved by using an explicit method with adaptive time stepping. In this work, we propose a fully explicit method for the solution of the decoupled monodomain model. In contrast to semi‐implicit methods, fully explicit methods present lower memory footprint and higher scalability. However, such methods are only conditionally stable. We overcome the conditional stability limitation by proposing a dual adaptive explicit method in which adaptive time integration is applied for the solution of both the reaction and diffusion terms. We perform a set of numerical examples where cardiac propagation is simulated under physiological and pathophysiological conditions. Results show that the proposed method presents preserved accuracy and improved computational efficiency as compared to standard operator splitting‐based methods.

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Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na⁺‐Ca²⁺‐Ca²⁺/calmodulin‐dependent protein kinase II‐reactive oxygen species feedback

Morotti

Grandi

2018

WIREs Mechanisms of Disease

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Quantitative systems modeling aims to integrate knowledge in different research areas with models describing biological mechanisms and dynamics to gain a better understanding of complex clinical syndromes. Heart failure (HF) is a chronic complex cardiac disease that results from structural or functional disorders impairing the ability of the ventricle to fill with or eject blood. Highly interactive and dynamic changes in mechanical, structural, neurohumoral, metabolic, and electrophysiological properties collectively predispose the failing heart to cardiac arrhythmias, which are responsible for about a half of HF deaths. Multiscale cardiac modeling and simulation integrate structural and functional data from HF experimental models and patients to improve our mechanistic understanding of this complex arrhythmia syndrome. In particular, they allow investigating how disease-induced remodeling alters the coupling of electrophysiology, Ca and Na handling, contraction, and energetics that lead to rhythm derangements. The Ca /calmodulin-dependent protein kinase II, which expression and activity are enhanced in HF, emerges as a critical hub that modulates the feedbacks between these various subsystems and promotes arrhythmogenesis. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Cellular Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models.

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Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

Cited by 31 publications

References 63 publications

Intermittent Failure Dynamics Characterization

Intermittent Failure Dynamics Characterization

A dual adaptive explicit time integration algorithm for efficiently solving the cardiac monodomain equation

Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na⁺‐Ca²⁺‐Ca²⁺/calmodulin‐dependent protein kinase II‐reactive oxygen species feedback

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Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

Cited by 31 publications

References 63 publications

Intermittent Failure Dynamics Characterization

Intermittent Failure Dynamics Characterization

A dual adaptive explicit time integration algorithm for efficiently solving the cardiac monodomain equation

Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na+‐Ca2+‐Ca2+/calmodulin‐dependent protein kinase II‐reactive oxygen species feedback

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Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na⁺‐Ca²⁺‐Ca²⁺/calmodulin‐dependent protein kinase II‐reactive oxygen species feedback