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      Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 4 , 9 , 1 , 5 , 10 , 11 , 12 , 8 , 9 , 10 , 7 , 13 , 9 , 14 , 4 , 15 , 9 , 5 , 1 , 13 , 14 , 2 , 6 , 6 , 7 , 1
      Proceedings. Mathematical, Physical, and Engineering Sciences / The Royal Society
      The Royal Society Publishing
      cardiac mechanics, verification, benchmark, VVUQ

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          Abstract

          Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.

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          Most cited references12

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          Verification of cardiac tissue electrophysiology simulators using an N-version benchmark.

          Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future.
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            Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease.

            Actin-myosin interactions provide the driving force underlying each heartbeat. The current view is that actin-bound regulatory proteins play a dominant role in the activation of calcium-dependent cardiac muscle contraction. In contrast, the relevance and nature of regulation by myosin regulatory proteins (for example, myosin light chain-2 [MLC2]) in cardiac muscle remain poorly understood. By integrating gene-targeted mouse and computational models, we have identified an indispensable role for ventricular Mlc2 (Mlc2v) phosphorylation in regulating cardiac muscle contraction. Cardiac myosin cycling kinetics, which directly control actin-myosin interactions, were directly affected, but surprisingly, Mlc2v phosphorylation also fed back to cooperatively influence calcium-dependent activation of the thin filament. Loss of these mechanisms produced early defects in the rate of cardiac muscle twitch relaxation and ventricular torsion. Strikingly, these defects preceded the left ventricular dysfunction of heart disease and failure in a mouse model with nonphosphorylatable Mlc2v. Thus, there is a direct and early role for Mlc2 phosphorylation in regulating actin-myosin interactions in striated muscle contraction, and dephosphorylation of Mlc2 or loss of these mechanisms can play a critical role in heart failure.
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              Simulation of the contraction of the ventricles in a human heart model including atria and pericardium.

              During the contraction of the ventricles, the ventricles interact with the atria as well as with the pericardium and the surrounding tissue in which the heart is embedded. The atria are stretched, and the atrioventricular plane moves toward the apex. The atrioventricular plane displacement (AVPD) is considered to be a major contributor to the ventricular function, and a reduced AVPD is strongly related to heart failure. At the same time, the epicardium slides almost frictionlessly on the pericardium with permanent contact. Although the interaction between the ventricles, the atria and the pericardium plays an important role for the deformation of the heart, this aspect is usually not considered in computational models. In this work, we present an electromechanical model of the heart, which takes into account the interaction between ventricles, pericardium and atria and allows to reproduce the AVPD. To solve the contact problem of epicardium and pericardium, a contact handling algorithm based on penalty formulation was developed, which ensures frictionless and permanent contact. Two simulations of the ventricular contraction were conducted, one with contact handling of pericardium and heart and one without. In the simulation with contact handling, the atria were stretched during the contraction of the ventricles, while, due to the permanent contact with the pericardium, their volume increased. In contrast to that, in the simulations without pericardium, the atria were also stretched, but the change in the atrial volume was much smaller. Furthermore, the pericardium reduced the radial contraction of the ventricles and at the same time increased the AVPD.
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                Author and article information

                Journal
                Proc Math Phys Eng Sci
                Proc. Math. Phys. Eng. Sci
                RSPA
                royprsa
                Proceedings. Mathematical, Physical, and Engineering Sciences / The Royal Society
                The Royal Society Publishing
                1364-5021
                1471-2946
                8 December 2015
                8 December 2015
                : 471
                : 2184
                : 20150641
                Affiliations
                [1 ]Department of Biomedical Engineering, King's College London, London, UK
                [2 ]Thomas J. Watson Research Center, IBM Research, Yorktown Heights, NY 10598, USA
                [3 ]Department of Physics and Astronomy, Ghent University , Ghent, Belgium
                [4 ]Institute of Biophysics, Medical University of Graz , Graz, Austria
                [5 ]Institute of Biomedical Engineering, Karlsruhe Institute of Technology , Karlsruhe, Germany
                [6 ]Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University , Baltimore, MD 21218, USA
                [7 ]Auckland Bioengineering Institute, University of Auckland , Auckland, New Zealand
                [8 ]Department of Structural and Geotechnical Engineering, Pontifica Universidad Católica de Chile , Chile
                [9 ]Center for Computational Medicine in Cardiology, Institute of Computational Science, Università della Svizzera italiana , Lugano, Switzerland
                [10 ]School of Mathematics and Statistics, University of Glasgow , Glasgow, UK
                [11 ]Department of Engineering, Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico of Rome , Rome, Italy
                [12 ]Interdisciplinary Applied Mathematics Center, University of North Carolina at Chapel Hill , Chapel Hill, NC, USA
                [13 ]Department of Engineering Science, University of Auckland , Auckland, New Zealand
                [14 ]Simula Research Laboratory, Fornebu, Norway
                [15 ]Civil and Environmental Engineering Department, Duke University , Durham, NC 27708-0287, USA
                Author notes
                Author information
                http://orcid.org/0000-0001-8572-251X
                Article
                rspa20150641
                10.1098/rspa.2015.0641
                4707707
                26807042
                0f470fe7-d748-4ad0-9304-d726d867c017
                © 2015 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 9 September 2015
                : 30 October 2015
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council, http://dx.doi.org/10.13039/501100000268;
                Award ID: BB/J017272/1
                Categories
                1006
                26
                44
                47
                Research Articles
                Custom metadata
                December 8, 2015

                Physics
                cardiac mechanics,verification,benchmark,vvuq
                Physics
                cardiac mechanics, verification, benchmark, vvuq

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