Application of In Silico Trials for the Investigation of Drug Effects on Cardiomyopathy-Diseased Heart Cycle Properties

Miljan Milosevic; Bogdan Milicevic; Vladimir Simic; Milos Anic; Milos Kojic; Djordje Jakovljevic; Nenad Filipovic

doi:10.3390/app132111780

Application of In Silico Trials for the Investigation of Drug Effects on Cardiomyopathy-Diseased Heart Cycle Properties

Miljan Milosevic, Bogdan Milicevic, Vladimir Simic, Milos Anic, Milos Kojic, Djordje Jakovljevic, Nenad Filipovic

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Abstract

In this paper, we present the abilities of an in silico platform used to simulate the effects of different drugs on heartbeat cycle performance. The platform is based on a finite element modelling approach with the fluid–solid interaction implemented using a loose coupling procedure. Active mechanical stresses are calculated using the Hunter excitation model while the passive mechanical stresses are calculated using a recently introduced experiment-based material model for the heart tissue. The applicability of the platform is illustrated using a simple parametric model of the left ventricle. The simulations are performed using parameters that are specific to drugs such as digoxin, mavacamten, 2-deoxy adenosine triphosphate, and disopyramide, with the concentration of calcium in the cardiac cells affected by these drugs given as an input function. The results are obtained for two geometries mimicking patients with hypertrophic and dilated cardiomyopathy, and also for different inlet/outlet boundary conditions simulating different drug effects at the macroscopic level. Using in silico simulations with virtual patients, it is possible to evaluate the influence of different drugs on cardiac output and ejection fraction. This approach can significantly reduce computational costs with an acceptable solution accuracy compared to approaches coupling finite element and biophysical muscle model methods that are used to calculate drug effects at the micro level.

Original language	English
Article number	11780
Number of pages	15
Journal	Applied Sciences
Volume	13
Issue number	21
DOIs	https://doi.org/10.3390/app132111780 https://doi.org/10.3390/app132111780
Publication status	Published - 27 Oct 2023
Externally published	Yes

Bibliographical note

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Funder

This project received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement no. 101080905, funded by the European Union. The views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the granting authority—the European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. The research was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia, contract number 451-03-47/2023-01/200378 (Institute of Information Technologies, University of Kragujevac) and 451-03-68/2023-14/200107 (Faculty of Engineering, University of Kragujevac)].

Keywords

cardiac cycle
cardiomyopathy
finite element method
left ventricle model

ASJC Scopus subject areas

Materials Science(all)
Instrumentation
Engineering(all)
Process Chemistry and Technology
Computer Science Applications
Fluid Flow and Transfer Processes

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abstract = "In this paper, we present the abilities of an in silico platform used to simulate the effects of different drugs on heartbeat cycle performance. The platform is based on a finite element modelling approach with the fluid–solid interaction implemented using a loose coupling procedure. Active mechanical stresses are calculated using the Hunter excitation model while the passive mechanical stresses are calculated using a recently introduced experiment-based material model for the heart tissue. The applicability of the platform is illustrated using a simple parametric model of the left ventricle. The simulations are performed using parameters that are specific to drugs such as digoxin, mavacamten, 2-deoxy adenosine triphosphate, and disopyramide, with the concentration of calcium in the cardiac cells affected by these drugs given as an input function. The results are obtained for two geometries mimicking patients with hypertrophic and dilated cardiomyopathy, and also for different inlet/outlet boundary conditions simulating different drug effects at the macroscopic level. Using in silico simulations with virtual patients, it is possible to evaluate the influence of different drugs on cardiac output and ejection fraction. This approach can significantly reduce computational costs with an acceptable solution accuracy compared to approaches coupling finite element and biophysical muscle model methods that are used to calculate drug effects at the micro level.",

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Application of In Silico Trials for the Investigation of Drug Effects on Cardiomyopathy-Diseased Heart Cycle Properties

Abstract

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Keywords

ASJC Scopus subject areas

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