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How drugs modulate the performance of the human heart

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Abstract

Many drugs interact with ion channels in the cells of our heart and trigger heart rhythm disorders with potentially fatal consequences. Computational modeling can provide mechanistic insight into the onset and propagation of drug-induced arrhythmias, but the effect of drugs on the mechanical performance of the heart remains poorly understood. Here we establish a multiphysics framework that integrates the biochemical, electrical, and mechanical effects of drugs, from cellular excitation to cardiac contraction. For the example of the drug dofetilide, we show that drug concentrations of 5x and 8x increase the heart rate to 122 and 114 beats per minute, increase myofiber stretches by 5%, and decrease overall tissue relaxation by 6%. This results in inter-ventricular and atrial-ventricular dyssynchronies and changes in cardiac output by \(-2.5\)% and +7%. Our results emphasize the need for multiphysics modeling to better understand the mechanical implications of drug-induced arrhythmias. Knowing how different drug concentrations affect the performance of the heart has important clinical implications in drug safety evaluation and personalized medicine.

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Acknowledgements

This work used the Extreme Science and Engineering Discovery Environment (XSEDE) project TG-MSS170033 supported by the National Science Foundation Grant Number ACI-1548562, by a Belgian American Education Foundation Postdoctoral Research Fellowship, a Stanford Bio-X IIP Seed Grant, and the National Institutes of Health Grant R01HL131975.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Stanford University, Stanford, CA, USA

    M. Peirlinck

  2. Department of Biomechanical Engineering, Delft University of Technology, Delft, Netherlands

    M. Peirlinck

  3. Dassault Systemes Simulia Corporation, Johnston, RI, USA

    J. Yao

  4. Department of Mechanical Engineering, Pontificia Universidad Catholica de Chile, Santiago, Chile

    F. Sahli Costabal

  5. Departments of Mechanical Engineering and Bioengineering, Stanford University, Stanford, CA, USA

    E. Kuhl

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  1. M. Peirlinck
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Peirlinck, M., Yao, J., Sahli Costabal, F. et al. How drugs modulate the performance of the human heart. Comput Mech 69, 1397–1411 (2022). https://doi.org/10.1007/s00466-022-02146-1

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