scispace - formally typeset
Open accessJournal ArticleDOI: 10.1093/EUROPACE/EUAA405

Human biventricular electromechanical simulations on the progression of electrocardiographic and mechanical abnormalities in post-myocardial infarction.

04 Mar 2021-Europace (Oxford University Press (OUP))-Vol. 23
Abstract: AIMS Develop, calibrate and evaluate with clinical data a human electromechanical modelling and simulation framework for multiscale, mechanistic investigations in healthy and post-myocardial infarction (MI) conditions, from ionic to clinical biomarkers. METHODS AND RESULTS Human healthy and post-MI electromechanical simulations were conducted with a novel biventricular model, calibrated and evaluated with experimental and clinical data, including torso/biventricular anatomy from clinical magnetic resonance, state-of-the-art human-based membrane kinetics, excitation-contraction and active tension models, and orthotropic electromechanical coupling. Electromechanical remodelling of the infarct/ischaemic region and the border zone were simulated for ischaemic, acute, and chronic states in a fully transmural anterior infarct and a subendocardial anterior infarct. The results were compared with clinical electrocardiogram and left ventricular ejection fraction (LVEF) data at similar states. Healthy model simulations show LVEF 63%, with 11% peak systolic wall thickening, QRS duration and QT interval of 100 ms and 330 ms. LVEF in ischaemic, acute, and chronic post-MI states were 56%, 51%, and 52%, respectively. In linking the three post-MI simulations, it was apparent that elevated resting potential due to hyperkalaemia in the infarcted region led to ST-segment elevation, while a large repolarization gradient corresponded to T-wave inversion. Mechanically, the chronic stiffening of the infarct region had the benefit of improving systolic function by reducing infarct bulging at the expense of reducing diastolic function by inhibiting inflation. CONCLUSION Our human-based multiscale modelling and simulation framework enables mechanistic investigations into patho-physiological electrophysiological and mechanical behaviour and can serve as testbed to guide the optimization of pharmacological and electrical therapies.

... read more

Topics: QRS complex (50%)
Citations
  More

6 results found


Open accessJournal ArticleDOI: 10.3390/MATH9151785
28 Jul 2021-
Abstract: β-adrenergic receptor stimulation (β-ARS) is a physiological mechanism that regulates cardiovascular function under stress conditions or physical exercise. Triggered during the so-called “fight-or-flight” response, the activation of the β-adrenergic receptors located on the cardiomyocyte membrane initiates a phosphorylation cascade of multiple ion channel targets that regulate both cellular excitability and recovery and of different proteins involved in intracellular calcium handling. As a result, β-ARS impacts both the electrophysiological and the mechanical response of the cardiomyocyte. β-ARS also plays a crucial role in several cardiac pathologies, greatly modifying cardiac output and potentially causing arrhythmogenic events. Mathematical patient-specific models are nowadays envisioned as an important tool for the personalised study of cardiac disease, the design of tailored treatments, or to inform risk assessment. Despite that, only a reduced number of computational studies of heart disease have incorporated β-ARS modelling. In this review, we describe the main existing multiscale frameworks to equip cellular models of cardiac electrophysiology with a β-ARS response. We also outline various applications of these multiscale frameworks in the study of cardiac pathology. We end with a discussion of the main current limitations and the future steps that need to be taken to adapt these models to a clinical environment and to incorporate them in organ-level simulations.

... read more

4 Citations


Open accessJournal ArticleDOI: 10.1016/J.CMA.2021.114092
Abstract: Computer models of cardiac electro-mechanics (EM) show promise as an effective means for the quantitative analysis of clinical data and, potentially, for predicting therapeutic responses. To realize such advanced applications methodological key challenges must be addressed. Enhanced computational efficiency and robustness is crucial to facilitate, within tractable time frames, model personalization, the simulation of prolonged observation periods under a broad range of conditions, and physiological completeness encompassing therapy-relevant mechanisms is needed to endow models with predictive capabilities beyond the mere replication of observations. Here, we introduce a universal feature-complete cardiac EM modeling framework that builds on a flexible method for coupling a 3D model of bi-ventricular EM to the physiologically comprehensive 0D CircAdapt model representing atrial mechanics and closed-loop circulation. A detailed mathematical description is given and efficiency, robustness, and accuracy of numerical scheme and solver implementation are evaluated. After parameterization and stabilization of the coupled 3D–0D model to a limit cycle under baseline conditions, the model’s ability to replicate physiological behaviors is demonstrated, by simulating the transient response to alterations in loading conditions and contractility, as induced by experimental protocols used for assessing systolic and diastolic ventricular properties. Mechanistic completeness and computational efficiency of this novel model render advanced applications geared towards predicting acute outcomes of EM therapies feasible.

... read more

3 Citations


Book ChapterDOI: 10.1007/978-3-030-78710-3_34
Lei Wang1, Zhinuo J. Wang1, Ruben Doste1, Alfonso Santiago  +4 moreInstitutions (1)
21 Jun 2021-
Abstract: The helix orientated fibres in the ventricular wall modulate the cardiac electromechanical functions. Experimental data of the helix angle through the ventricular wall have been reported from histological and image-based methods, exhibiting large variability. It is, however, still unclear how this variability influences electrocardiographic characteristics and mechanical functions of human hearts, as characterized through computer simulations. This paper investigates the effects of the range and transmural gradient of the helix angle on electrocardiogram, pressure-volume loops, circumferential contraction, wall thickening, longitudinal shortening and twist, by using state-of-the-art computational human biventricular modelling and simulation. Five models of the helix angle are considered based on in vivo diffusion tensor magnetic resonance imaging data. We found that both electrocardiographic and mechanical biomarkers are influenced by these two factors, through the mechanism of regulating the proportion of circumferentially-orientated fibres. With the increase in this proportion, the T-wave amplitude decreases, circumferential contraction and twist increase while longitudinal shortening decreases.

... read more

Topics: Helix angle (57%)

Open accessJournal ArticleDOI: 10.3389/FPHYS.2021.716597
Renee Miller1, Eric Kerfoot1, Charlene Mauger2, Tevfik F Ismail1  +4 moreInstitutions (3)
Abstract: Parameterised patient-specific models of the heart enable quantitative analysis of cardiac function as well as estimation of regional stress and intrinsic tissue stiffness. However, the development of personalised models and subsequent simulations have often required lengthy manual setup, from image labelling through to generating the finite element model and assigning boundary conditions. Recently, rapid patient-specific finite element modelling has been made possible through the use of machine learning techniques. In this paper, utilising multiple neural networks for image labelling and detection of valve landmarks, together with streamlined data integration, a pipeline for generating patient-specific biventricular models is applied to clinically-acquired data from a diverse cohort of individuals, including hypertrophic and dilated cardiomyopathy patients and healthy volunteers. Valve motion from tracked landmarks as well as cavity volumes measured from labelled images are used to drive realistic motion and estimate passive tissue stiffness values. The neural networks are shown to accurately label cardiac regions and features for these diverse morphologies. Furthermore, differences in global intrinsic parameters, such as tissue anisotropy and normalised active tension, between groups illustrate respective underlying changes in tissue composition and/or structure as a result of pathology. This study shows the successful application of a generic pipeline for biventricular modelling, incorporating artificial intelligence solutions, within a diverse cohort.

... read more


Open accessPosted Content
Abstract: Fiber-reinforced soft biological tissues are typically modeled as hyperelastic, anisotropic, and nearly incompressible materials. To enforce incompressibility a multiplicative split of the deformation gradient into a volumetric and an isochoric part is a very common approach. However, due to the high stiffness of anisotropic materials in the preferred directions, the finite element analysis of such problems often suffers from severe locking effects and numerical instabilities. In this paper, we present novel methods to overcome locking phenomena for anisotropic materials using stabilized P1-P1 elements. We introduce different stabilization techniques and demonstrate the high robustness and computational efficiency of the chosen methods. In several benchmark problems we compare the approach to standard linear elements and show the accuracy and versatility of the methods to simulate anisotropic, nearly and fully incompressible materials. We are convinced that this numerical framework offers the possibility to accelerate accurate simulations of biological tissues, enabling patient-specfic parameterization studies, which require numerous forward simulations.

... read more


References
  More

31 results found


Open accessJournal ArticleDOI: 10.1161/01.CIR.101.23.E215
13 Jun 2000-Circulation
Abstract: —The newly inaugurated Research Resource for Complex Physiologic Signals, which was created under the auspices of the National Center for Research Resources of the National Institutes of He...

... read more

8,656 Citations


Open accessJournal ArticleDOI: 10.1093/EURHEARTJ/EHV316
Abstract: ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AGNES : Arrhythmia Genetics in the Netherlands AHA : American Heart Association AMIOVIRT : AMIOdarone Versus Implantable cardioverter-defibrillator:

... read more

Topics: Sudden cardiac death (62%), Implantable cardioverter-defibrillator (60%), Amiodarone (55%) ... show more

2,185 Citations


Open accessJournal ArticleDOI: 10.1093/EUROPACE/EUV319
01 Nov 2015-Europace
Abstract: ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AGNES : Arrhythmia Genetics in the Netherlands AHA : American Heart Association AMIOVIRT : AMIOdarone Versus Implantable cardioverter-defibrillator:

... read more

Topics: Sudden cardiac death (62%), Implantable cardioverter-defibrillator (60%), Amiodarone (55%) ... show more

1,465 Citations


Open accessJournal ArticleDOI: 10.1016/J.CPCARDIOL.2009.10.002
Abstract: Coronary heart disease (CHD) is the single largest cause of death in the developed countries and is one of the leading causes of disease burden in developing countries. In 2001, there were 7.3 million deaths due to CHD worldwide. Three-fourths of global deaths due to CHD occurred in the low- and middle-income countries. The rapid rise in CHD burden in most of the low- and middle-income countries is due to socio-economic changes, increase in lifespan, and acquisition of lifestyle-related risk factors. The CHD death rate, however, varies dramatically across the developing countries. The varying incidence, prevalence, and mortality rates reflect the different levels of risk factors, other competing causes of death, availability of resources to combat cardiovascular disease, and the stage of epidemiologic transition that each country or region finds itself. The economic burden of CHD is equally large but solutions exist to manage this growing burden.

... read more

Topics: Disease burden (60%), Mortality rate (56%), Cause of death (51%)

767 Citations


Journal ArticleDOI: 10.1056/NEJMOA043938
Abstract: Background The risk of sudden death from cardiac causes is increased among survivors of acute myocardial infarction with reduced left ventricular systolic function. We assessed the risk and time course of sudden death in high-risk patients after myocardial infarction. Methods We studied 14,609 patients with left ventricular dysfunction, heart failure, or both after myocardial infarction to assess the incidence and timing of sudden unexpected death or cardiac arrest with resuscitation in relation to the left ventricular ejection fraction. Results Of 14,609 patients, 1067 (7 percent) had an event a median of 180 days after myocardial infarction: 903 died suddenly, and 164 were resuscitated after cardiac arrest. The risk was highest in the first 30 days after myocardial infarction — 1.4 percent per month (95 percent confidence interval, 1.2 to 1.6 percent) — and decreased to 0.14 percent per month (95 percent confidence interval, 0.11 to 0.18 percent) after 2 years. Patients with a left ventricular ejection ...

... read more

699 Citations