Journal articles on the topic 'Cardiovascular multiscale modelling'
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Vergara, Christian, and Paolo Zunino. "Multiscale Boundary Conditions for Drug Release from Cardiovascular Stents." Multiscale Modeling & Simulation 7, no. 2 (January 2008): 565–88. http://dx.doi.org/10.1137/07070214x.
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Cerutti, Sergio, Dirk Hoyer, and Andreas Voss. "Multiscale, multiorgan and multivariate complexity analyses of cardiovascular regulation." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 367, no. 1892 (February 27, 2009): 1337–58. http://dx.doi.org/10.1098/rsta.2008.0267.
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Cardiovascular system complexity is confirmed by both its generally variegated structure of physiological modelling and the richness of information detectable from processing of the signals involved in it, with strong linear and nonlinear interactions with other biological systems. In particular, this behaviour may be accordingly described by means of what we call MMM paradigm (i.e. multiscale, multiorgan and multivariate). Such an approach to the cardiovascular system emphasizes where the genesis of its complexity is potentially allocated and how it is possible to detect information from it. No doubt that processing signals from multi-leads of the same system (multivariate), from the interaction of different physiological systems (multiorgan) and integrating all this information across multiple scales (from genes, to proteins, molecules, cells, up to the whole organ) could really provide us with a more complete look at the overall phenomenon of cardiovascular system complexity, with respect to the one which is obtainable from its single constituent parts. In this paper, some examples of approaches are discussed for investigating the cardiovascular system in different time and spatial scales, in studying a different organ involvement (such as sleep, depression and multiple organ dysfunction) and in using a multivariate approach via various linear and nonlinear methods for cardiovascular risk stratification and pathology assessment.
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Chabiniok, Radomir, Vicky Y. Wang, Myrianthi Hadjicharalambous, Liya Asner, Jack Lee, Maxime Sermesant, Ellen Kuhl, et al. "Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics." Interface Focus 6, no. 2 (April 6, 2016): 20150083. http://dx.doi.org/10.1098/rsfs.2015.0083.
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With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.
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Doste, Ruben, and Alfonso Bueno-Orovio. "Multiscale Modelling of β-Adrenergic Stimulation in Cardiac Electromechanical Function." Mathematics 9, no. 15 (July 28, 2021): 1785. http://dx.doi.org/10.3390/math9151785.
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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.
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Nikolić, Jovana, Aleksandar Atanasijević, Andreja Živić, Tijana Šušteršič, Miloš Ivanović, and Nenad Filipović. "Development of SGABU Platform for Multiscale Modeling." Ipsi Transactions on Internet research 18, no. 1 (January 1, 2022): 50–55. http://dx.doi.org/10.58245/ipsi.tir.22jr.09.
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SGABU platform was created as a computational platform for multiscale modelling in biomedical engineering. This is one of the few proposed integrated platforms that include different areas of bioengineering. The platform includes already developed solutions, various datasets and models related to cancer, cardiovascular, bone disorders, and tissue engineering. The biggest obstacle in designing a platform of this type is the use of different tools for each of the layers of architecture for models which are created using different technologies and their integration and visualization within a platform. This study describes the technologies that were used for building the platform and methods for data and models visualization. The goal was to build the most flexible system capable of executing tools of various nature and connecting them into a platform.
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HAREWOOD, F., J. GROGAN, and P. McHUGH. "A MULTISCALE APPROACH TO FAILURE ASSESSMENT IN DEPLOYMENT FOR CARDIOVASCULAR STENTS." Journal of Multiscale Modelling 02, no. 01n02 (March 2010): 1–22. http://dx.doi.org/10.1142/s1756973710000278.
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Cardiovascular stents are tiny scaffolds that are used in the treatment of heart disease. The recent development of drug-eluting stents has lead to stent implantation in arterial regions that would previously have been considered too complex. Deployment in these tortuous and branched regions results in an increased deformation of the stent. It is thus important to assess whether there is an increased likelihood of stent failure in deployment in such regions. A multiscale approach, incorporating the results of microscale modeling of failure in individual stent struts and macroscale modeling of stent deployment in realistic arterial geometries is considered in this work. Such an approach allows for a more accurate assessment of failure than is obtainable through the macroscale modeling of deployment in idealized arterial geometries alone, as is presented in previous studies. Results give an insight into failure risks for different stent implantation scenarios: stent failure is unlikely in deployment in tortuous vessels, however there may be risks associated with certain bifurcational stenting techniques.
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Quarteroni, A., A. Manzoni, and C. Vergara. "The cardiovascular system: Mathematical modelling, numerical algorithms and clinical applications." Acta Numerica 26 (May 1, 2017): 365–590. http://dx.doi.org/10.1017/s0962492917000046.
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Mathematical and numerical modelling of the cardiovascular system is a research topic that has attracted remarkable interest from the mathematical community because of its intrinsic mathematical difficulty and the increasing impact of cardiovascular diseases worldwide. In this review article we will address the two principal components of the cardiovascular system: arterial circulation and heart function. We will systematically describe all aspects of the problem, ranging from data imaging acquisition, stating the basic physical principles, analysing the associated mathematical models that comprise PDE and ODE systems, proposing sound and efficient numerical methods for their approximation, and simulating both benchmark problems and clinically inspired problems. Mathematical modelling itself imposes tremendous challenges, due to the amazing complexity of the cardiocirculatory system, the multiscale nature of the physiological processes involved, and the need to devise computational methods that are stable, reliable and efficient. Critical issues involve filtering the data, identifying the parameters of mathematical models, devising optimal treatments and accounting for uncertainties. For this reason, we will devote the last part of the paper to control and inverse problems, including parameter estimation, uncertainty quantification and the development of reduced-order models that are of paramount importance when solving problems with high complexity, which would otherwise be out of reach.
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Takizawa, Kenji, Yuri Bazilevs, Tayfun E. Tezduyar, Christopher C. Long, Alison L. Marsden, and Kathleen Schjodt. "ST and ALE-VMS methods for patient-specific cardiovascular fluid mechanics modeling." Mathematical Models and Methods in Applied Sciences 24, no. 12 (August 15, 2014): 2437–86. http://dx.doi.org/10.1142/s0218202514500250.
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This paper provides a review of the space–time (ST) and Arbitrary Lagrangian–Eulerian (ALE) techniques developed by the first three authors' research teams for patient-specific cardiovascular fluid mechanics modeling, including fluid–structure interaction (FSI). The core methods are the ALE-based variational multiscale (ALE-VMS) method, the Deforming-Spatial-Domain/Stabilized ST formulation, and the stabilized ST FSI technique. A good number of special techniques targeting cardiovascular fluid mechanics have been developed to be used with the core methods. These include: (i) arterial-surface extraction and boundary condition techniques, (ii) techniques for using variable arterial wall thickness, (iii) methods for calculating an estimated zero-pressure arterial geometry, (iv) techniques for prestressing of the blood vessel wall, (v) mesh generation techniques for building layers of refined fluid mechanics mesh near the arterial walls, (vi) a special mapping technique for specifying the velocity profile at an inflow boundary with non-circular shape, (vii) a scaling technique for specifying a more realistic volumetric flow rate, (viii) techniques for the projection of fluid–structure interface stresses, (ix) a recipe for pre-FSI computations that improve the convergence of the FSI computations, (x) the Sequentially-Coupled Arterial FSI technique and its multiscale versions, (xi) techniques for calculation of the wall shear stress (WSS) and oscillatory shear index (OSI), (xii) methods for stent modeling and mesh generation, (xiii) methods for calculation of the particle residence time, and (xiv) methods for an estimated element-based zero-stress state for the artery. Here we provide an overview of the special techniques for WSS and OSI calculations, stent modeling and mesh generation, and calculation of the residence time with application to pulsatile ventricular assist device (PVAD). We provide references for some of the other special techniques. With results from earlier computations, we show how these core and special techniques work.
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Gao, Yufang, and Zongguo Zhang. "Modelling and Analysis of Complex Viscous Fluid in Thin Elastic Tubes." Complexity 2020 (September 15, 2020): 1–10. http://dx.doi.org/10.1155/2020/9256845.
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Cardiovascular disease is a major threat to human health. The study on the pathogenesis and prevention of cardiovascular disease has received special attention. In this paper, we have contributed to the derivation of a mathematical model for the nonlinear waves in an artery. From the Navier–Stokes equations and continuity equation, the vorticity equation satisfied by the blood flow is established. And based on the multiscale analysis and perturbation method, a new model of the Boussinesq equation with viscous term is derived to describe the propagation of a viscous fluid through a thin tube. In order to be more consistent with the flow of the fluid, the time-fractional Boussinesq equation with viscous term is deduced by employing the semi-inverse method and the fractional variational principle. Moreover, the approximate analytical solution of the fractional equation is obtained, and the effect of viscosity on the amplitude and width of the wave is studied. Finally, the effects of the fractional order parameters and vessel radius on blood flow volume are discussed and analyzed.
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Dupuis, Lauren J., Theo Arts, Frits W. Prinzen, Tammo Delhaas, and Joost Lumens. "Linking cross-bridge cycling kinetics to response to cardiac resynchronization therapy: a multiscale modelling study." EP Europace 20, suppl_3 (November 1, 2018): iii87—iii93. http://dx.doi.org/10.1093/europace/euy230.
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Canuto, Daniel, Kwitae Chong, Cayley Bowles, Erik P. Dutson, Jeff D. Eldredge, and Peyman Benharash. "A regulated multiscale closed-loop cardiovascular model, with applications to hemorrhage and hypertension." International Journal for Numerical Methods in Biomedical Engineering 34, no. 6 (April 19, 2018): e2975. http://dx.doi.org/10.1002/cnm.2975.
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Gladding, P. A., N. James, and W. Hewitt. "A057 Multiscale Predictive Modelling in Heart Failure: Machine Learning Applied to Big Data, Imaging and Multiomics." Heart, Lung and Circulation 29 (2020): S24—S25. http://dx.doi.org/10.1016/j.hlc.2020.05.062.
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Boyle, Patrick M., Juan Carlos del Álamo, and Nazem Akoum. "Fibrosis, atrial fibrillation and stroke: clinical updates and emerging mechanistic models." Heart 107, no. 2 (October 23, 2020): 99–105. http://dx.doi.org/10.1136/heartjnl-2020-317455.
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The current paradigm of stroke risk assessment and mitigation in patients with atrial fibrillation (AF) is centred around clinical risk factors which, in the presence of AF, lead to thrombus formation. The mechanisms by which these clinical risk factors lead to thromboembolism, including any role played by atrial fibrosis, are not understood. In patients who had embolic stroke of undetermined source (ESUS), the problem is compounded by the absence of AF in a majority of patients despite long-term monitoring. Atrial fibrosis has emerged as a unifying mechanism that independently provides a substrate for arrhythmia and thrombus formation. Fibrosis-based computational models of AF initiation and maintenance promise to identify therapeutic targets in catheter ablation. In ESUS, fibrosis is also increasingly recognised as a major risk factor, but the underlying mechanism of this correlation is unclear. Simulations have uncovered potential vulnerability to arrhythmia induction in patients who had ESUS. Likewise, computational models of fluid dynamics representing blood flow in the left atrium and left atrium appendage have improved our understanding of thrombus formation, in particular left atrium appendage shapes and blood flow changes influenced by atrial remodelling. Multiscale modelling of blood flow dynamics based on structural fibrotic and morphological changes with associated cellular and tissue electrical remodelling leading to electromechanical abnormalities holds tremendous promise in providing a mechanistic understanding of the clinical problem of thromboembolisation. We present a review of clinical knowledge alongside computational modelling frameworks and conclude with a vision of a future paradigm integrating simulations in formulating personalised treatment plans for each patient.
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migliavacca, francesco, katia laganà, giancarlo pennati, marc r. de leval, edward l. bove, and gabriele dubini. "global mathematical modelling of the norwood circulation: a multiscale approach for the study of the pulmonary and coronary arterial perfusions." Cardiology in the Young 14, S3 (October 2004): 71–76. http://dx.doi.org/10.1017/s1047951104006614.
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the norwood procedure involves three separate stages of operative corrections. the first stage involves re-fashioning the pulmonary trunk into a neo-aorta so that it is possible to establish an unrestricted systemic circulation. an interpositional, or systemic-to-pulmonary arterial, shunt is then created between the neo-aorta and the pulmonary arteries to allow pulmonary perfusion and gas exchange. two of the available options for the systemic-to-pulmonary shunt are the central shunt and the right modified blalock-taussig shunt. in the setting of a central shunt, pulmonary perfusion is derived from a conduit placed between the pulmonary arterial bed and the neo-aorta whereas, in the modified blalock-taussig shunt, the conduit is interposed between one of the pulmonary arteries and the brachiocephalic artery. in subsequent stages, pulmonary perfusion is provided directly by deoxygenated blood. this is achieved by connecting, first, the superior caval vein, and then the inferior caval vein, to the pulmonary arteries. it is usually during the second stage that the systemic-to-pulmonary shunt is removed.
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Wu, Hsien-Tsai, Cyuan-Cin Liu, Men-Tzung Lo, Po-Chun Hsu, An-Bang Liu, Kai-Yu Chang, and Chieh-Ju Tang. "Multiscale Cross-Approximate Entropy Analysis as a Measure of Complexity among the Aged and Diabetic." Computational and Mathematical Methods in Medicine 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/324325.
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Complex fluctuations within physiological signals can be used to evaluate the health of the human body. This study recruited four groups of subjects: young healthy subjects (Group 1,n=32), healthy upper middle-aged subjects (Group 2,n=36), subjects with well-controlled type 2 diabetes (Group 3,n=31), and subjects with poorly controlled type 2 diabetes (Group 4,n=24). Data acquisition for each participant lasted 30 minutes. We obtained data related to consecutive time series with R-R interval (RRI) and pulse transit time (PTT). Using multiscale cross-approximate entropy (MCE), we quantified the complexity between the two series and thereby differentiated the influence of age and diabetes on the complexity of physiological signals. This study used MCE in the quantification of complexity between RRI and PTT time series. We observed changes in the influences of age and disease on the coupling effects between the heart and blood vessels in the cardiovascular system, which reduced the complexity between RRI and PTT series.
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Zun, P. S., A. J. Narracott, C. Chiastra, J. Gunn, and A. G. Hoekstra. "Location-Specific Comparison Between a 3D In-Stent Restenosis Model and Micro-CT and Histology Data from Porcine In Vivo Experiments." Cardiovascular Engineering and Technology 10, no. 4 (September 17, 2019): 568–82. http://dx.doi.org/10.1007/s13239-019-00431-4.
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Abstract Background Coronary artery restenosis is an important side effect of percutaneous coronary intervention. Computational models can be used to better understand this process. We report on an approach for validation of an in silico 3D model of in-stent restenosis in porcine coronary arteries and illustrate this approach by comparing the modelling results to in vivo data for 14 and 28 days post-stenting. Methods This multiscale model includes single-scale models for stent deployment, blood flow and tissue growth in the stented vessel, including smooth muscle cell (SMC) proliferation and extracellular matrix (ECM) production. The validation procedure uses data from porcine in vivo experiments, by simulating stent deployment using stent geometry obtained from micro computed tomography (micro-CT) of the stented vessel and directly comparing the simulation results of neointimal growth to histological sections taken at the same locations. Results Metrics for comparison are per-strut neointimal thickness and per-section neointimal area. The neointimal area predicted by the model demonstrates a good agreement with the detailed experimental data. For 14 days post-stenting the relative neointimal area, averaged over all vessel sections considered, was 20 ± 3% in vivo and 22 ± 4% in silico. For 28 days, the area was 42 ± 3% in vivo and 41 ± 3% in silico. Conclusions The approach presented here provides a very detailed, location-specific, validation methodology for in silico restenosis models. The model was able to closely match both histology datasets with a single set of parameters. Good agreement was obtained for both the overall amount of neointima produced and the local distribution. It should be noted that including vessel curvature and ECM production in the model was paramount to obtain a good agreement with the experimental data.
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Šušteršič, Tijana, Jelena Marković, Aleksandar Atanasijević, Andreja Živić, Miloš Ivanović, and Nenad Filipović. "SGABU PLATFORM – INTEGRATED PLATFORM FOR BIOMEDICAL DATASETS AND MULTISCALE MODELS." Contemporary Materials 13, no. 2 (October 10, 2022). http://dx.doi.org/10.7251/comen2202140s.
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The purpose of the SGABU platform is to include various models and datasets in the area of multiscale modelling. The main aspect of SGABU platform are various datasets and multiscale models related to cancer, cardiovascular, bone and tissue disorders. From the point of view of the dataset integration, a task requires implementation of the user interface that includes manipulation with either tabular data, or most of the datasets required further tuning carried out by front-end developers employing technologies such as Angular, Plotly.js, Paraview Glance, etc. From the point of view of integration of the multiscale models, most of the simulation modules provided by SGABU platform are implemented as Common Workflow Language (CWL) workflows. This method is an obvious choice since it makes use of Docker containerization and a standardized way of representing inputs, outputs, and intermediate results, giving findability, accessibility, inter-operability and reusability (FAIR principles). The effort of providing CWL type workflows consists of two distinct actions: (1) developing CWL implementation on FES (Functional Engine Service) backend and (2) developing an appropriate UI. Such integrated platform demonstratеs the use of different modelling examples and illustratеs the learning process from idea to implementation.
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Lyon, A., T. Arts, T. Delhaas, J. Lumens, and AAB Van Veen. "Development of a multiscale electromechanical computer model from cell to hemodynamics." EP Europace 23, Supplement_3 (May 1, 2021). http://dx.doi.org/10.1093/europace/euab116.509.
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Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CVON eDETECT 2015-12 Background Patients with genetic cardiomyopathies mostly remain asymptomatic until the occurrence of life-threatening arrhythmias and sudden cardiac death. The responsible pro-arrhythmic mechanisms, as well as the indicators for pro-arrhythmia, often remain unclear. Current research approaches are commonly based on experimental animal models or clinical data obtained from mutation carriers. The translation (and bridging) of results obtained from experimental models to humans and scale integration of these findings remains challenging. As a consequence, clinical relevance is often disputed. In light of these challenges, computer modelling shows strong potential for its ability to capture the complex dynamics of the cardiovascular system across different scales. Purpose We therefore aim to develop a multiscale electromechanical computer model coupling electrophysiology, sarcomere dynamics (contractility), whole-heart function and hemodynamics to investigate mechanisms (resulting from genetic predisposition to cardiomyopathy) of arrhythmogenicity and cardiac dysfunction in these patients. Methods We coupled our previously published model of cellular electromechanics to the CircAdapt computer model of the heart and circulation. Electromechanical coupling was performed through the amount of calcium bound to troponin (as described in the cellular model). The same electrophysiological properties were assumed in all cardiac walls. Diffusion of calcium from the sarcolemmal space to the membrane was described phenomenologically through a resistance model. Results Simulated hemodynamics properties were in range with control values with LVEDV = 110.8mL, LVESV = 38.7mL, RVEDV = 99.2mL, mLAP = 10.2mmHg, mRAP = 4.0mmHg. At the cellular level, sarcolemmal calcium transients showed the effect of mechanical change as illustrated by the bump in CaT. This effect was attenuated at the membrane due to the effect of diffusion. Alterations in the functionality of molecular entities underlying calcium homeostasis recapitulated cellular experimental findings as expected illustrated by implementing changes in adrenergic signaling. Conclusions We have established a new multiscale electromechanical computer model describing electrophysiology, sarcomere mechanics and hemodynamics. The model simulates normal values in the control situation. Current work focusses on parameter sensitivity analysis and validation. Feeding this new model with experimentally obtained data from patient-specific models (ranging from individual cells to e.g. transgenic mouse models based on relevant mutations) therefore has potential to bridge the gap between pathogenic experimental models and patient data. This will add to the understanding of underlying mechanisms responsible for disease onset and progression, and furthermore could develop into a tool to identify patients/mutation carriers at risk for severe disease outcome. Abstract Figure.
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Saglietto, Andrea, Stefania Scarsoglio, Matteo Fois, Luca Ridolfi, Gaetano Maria De Ferrari, and Matteo Anselmino. "108 Atrial fibrillation effects on coronary perfusion across the different myocardial layers: a computational analysis." European Heart Journal Supplements 23, Supplement_G (December 1, 2021). http://dx.doi.org/10.1093/eurheartj/suab127.039.
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Abstract Aims Atrial fibrillation (AF) patients may present ischaemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct haemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. Methods and results A computational fluid dynamics analysis was performed by means of a 1D-0D multiscale model of the entire human cardiovascular system, characterized by a detailed mathematical modelling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall, and subendocardial layers). Three mean ventricular rates were simulated in both sinus rhythm (SR) and AF: 75, 100, 125 b.p.m. We conducted inter-layer and inter-frequency analysis of the ratio between mean beat-to-beat blood flow in AF compared to SR (Q¯AP/Q¯SR Inter-layer analysis showed that, for each simulated ventricular rate, Q¯AP/Q¯SR progressively decreased from the epicardial to the endocardial layer in the distal left coronary artery districts (P-values < 0.001 for both left anterior descending artery—LAD, and left circumflex artery—LCx), while this was not the case for the distal right coronary artery (RCA) district. Inter-frequency analysis showed that, focusing on each myocardial layer, Q¯AP/Q¯SR progressively worsened as the ventricular rates increased in all investigated microcirculatory districts (LAD, LCx, and RCA) (P-values < 0.001 for all layer-specific comparisons). Conclusions AF exerts direct haemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (LAD and LCx).
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Passini, E., F. Margara, and B. Rodriguez. "Computational investigation of drug-induced effects on human cardiac electro-mechanics." EP Europace 23, Supplement_3 (May 1, 2021). http://dx.doi.org/10.1093/europace/euab116.513.
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Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NC3Rs Infrastructure for Impart Award (NC/P001076/1) Wellcome Trust Senior Research Fellowship in Basic Biomedical Sciences (214290/Z/18/Z) Background Human-based computer modelling and simulations have been widely used in cardiac electrophysiology, to provide a better understanding of the ionic mechanisms underlying risk of arrhythmias, and their modulation by drugs and diseased conditions. More recently, multiscale computer models of human cardiac electro-mechanics have been developed. These models provide the means for a comprehensive investigation of action potential, calcium transient, active force, and their variability in the population, and can predict drug-induced contractility changes in humans. Purpose This study aims to perform a computational investigation of variability in human cardiac contractility biomarkers and their modulation by well-known drugs. Methods We considered the most recent model of human ventricular electro-mechanics (Margara et al. 2020). We constructed a population of 300 cells by randomly varying the main ionic currents in the model, to represent the biological variability observed in human experimental data. We then simulated the effect of 10 reference compounds, 6 of which with known pro-arrhythmic risk. Simulations were performed at 1 Hz for multiple drug concentrations, using the Virtual Assay software. A set of action potential, calcium transient and active force biomarkers were computed, as well as the electro-mechanical window, and the occurrence of early after-depolarisations and after-contractions in the virtual population. Simulation results were compared against clinical risk of drug-induced arrhythmias and experimental recording from human ventricular myocytes from literature. Results Overall, biomarker variability in the virtual population increased following drug application compared to control conditions. All compounds had a negative inotropic effect in simulation, with a marked decrease of the active tension peak, e.g. -80% for nifedipine 8 nM. This is in agreement with human experimental data for all compounds except Dofetilide, for which no inotropic effect was observed in vitro. Compounds with known risk of arrhythmias provoked early after-depolarisations, which in turn caused after-contractions. Their occurrence in the population increased together with the drug concentration, e.g. 3.6% at 0.16 µM and 48% at 0.48 µM for droperidol. In addition, these compounds also displayed prolonged action potential and calcium transient, and a shortening of the electro-mechanical window, all known biomarkers of pro-arrhythmia. Conclusions We evaluated the effect and the cardiac safety of 10 reference compounds in a population of 300 human ventricular electro-mechanical models. Simulation results were in good agreement with experimental data in human ventricular cardiomyocytes, and they allowed to identify the compounds with a known pro-arrhythmic risk based on drug-induced early after-depolarisations and after-contractions. This methodology provides new insights into variability in human cardiac contractility and its modulation by drugs.