title: An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.
abstract: Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.
authors.affiliation: University College London, Mechanical Engineering Department, Torrington Place, WC1E 7JE London, UK. Electronic address: b.bhattacharya-ghosh@ucl.ac.uk.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bhattacharya-Ghosh
authors.affiliation: Eindhoven University of Technology, Biomedical Engineering, Materials Technology, PO Box 513, GEM-Z 4.18, 5600 MB, Eindhoven, The Netherlands. Electronic address: s.bozkurt@tue.nl.
authors.forename: Selim
authors.initials: S
authors.lastname: Bozkurt
authors.affiliation: Eindhoven University of Technology, Biomedical Engineering, Materials Technology, PO Box 513, GEM-Z 4.18, 5600 MB, Eindhoven, The Netherlands. Electronic address: m.c.m.rutten@tue.nl.
authors.forename: Marcel C M
authors.initials: MC
authors.lastname: Rutten
authors.affiliation: Eindhoven University of Technology, Biomedical Engineering, Materials Technology, PO Box 513, GEM-Z 4.18, 5600 MB, Eindhoven, The Netherlands. Electronic address: F.N.v.d.Vosse@tue.nl.
authors.forename: Frans N
authors.initials: FN
authors.lastname: van de Vosse
authors.affiliation: University College London, Mechanical Engineering Department, Torrington Place, WC1E 7JE London, UK. Electronic address: v.diaz@ucl.ac.uk.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Díaz-Zuccarini
mesh_terms: D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D019295:Computational Biology; D003198:Computer Simulation; D006321:Heart / Q000502:physiology; D006801:Humans; D008955:Models, Cardiovascular; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D017725:Ventricular Pressure / Q000502:physiology
chemical_list: D009124:Muscle Proteins; D002118:Calcium
keywords: Cardiovascular system; Heart failure; Idiopathic dilated cardiomyopathy; Modelling and simulation; Multi-scale modelling; Protein, cellular and organ level