Hemodynamic Effects of Alpha-Tropomyosin Mutations Associated with Inherited Cardiomyopathies: Multiscale Simulation

Fyodor Syomin, Albina Khabibullina, Anna Osepyan and Andrey Tsaturyan
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Fyodor Syomin: Institute of Mechanics, Lomonosov Moscow State University, 119192 Moscow, Russia
Albina Khabibullina: Mathematics and Mechanics Department, Lomonosov Moscow State University, 119991 Moscow, Russia
Anna Osepyan: Institute of Mechanics, Lomonosov Moscow State University, 119192 Moscow, Russia
Andrey Tsaturyan: Institute of Mechanics, Lomonosov Moscow State University, 119192 Moscow, Russia

Mathematics, 2020, vol. 8, issue 7, 1-19

Abstract: The effects of two cardiomyopathy-associated mutations in regulatory sarcomere protein tropomyosin (Tpm) on heart function were studied with a new multiscale model of the cardiovascular system (CVS). They were a Tpm mutation, Ile284Val, associated with hypertrophic cardiomyopathy (HCM), and an Asp230Asn one associated with dilated cardiomyopathy (DCM). When the molecular and cell-level changes in the Ca 2+ regulation of cardiac muscle caused by these mutations were introduced into the myocardial model of the left ventricle (LV) while the LV shape remained the same as in the model of the normal heart, the cardiac output and arterial blood pressure reduced. Simulations of LV hypertrophy in the case of the Ile284Val mutation and LV dilatation in the case of the Asp230Asn mutation demonstrated that the LV remodeling partially recovered the stroke volume and arterial blood pressure, confirming that both hypertrophy and dilatation help to preserve the LV function. The possible effects of changes in passive myocardial stiffness in the model according to data reported for HCM and DCM hearts were also simulated. The results of the simulations showed that the end-systolic pressure–volume relation that is often used to characterize heart contractility strongly depends on heart geometry and cannot be used as a characteristic of myocardial contractility.

Keywords: mathematical modeling; cardiac mechanics; multiscale simulation; cardiomyopathies; left ventricle remodeling (search for similar items in EconPapers)
JEL-codes: C (search for similar items in EconPapers)
Date: 2020
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