Cell to whole organ global sensitivity analysis on a four-chamber heart electromechanics model using Gaussian processes emulators
Author(s)
Type
Journal Article
Abstract
Cardiac pump function arises from a series of highly orchestrated events across multiple scales. Computational electromechanics can encode these events in physics-constrained models. However, the large number of parameters in these models has made the systematic study of the link between cellular, tissue, and organ scale parameters to whole heart physiology challenging. A patient-specific anatomical heart model, or digital twin, was created. Cellular ionic dynamics and contraction were simulated with the Courtemanche-Land and the ToR-ORd-Land models for the atria and the ventricles, respectively. Whole heart contraction was coupled with the circulatory system, simulated with CircAdapt, while accounting for the effect of the pericardium on cardiac motion. The four-chamber electromechanics framework resulted in 117 parameters of interest. The model was broken into five hierarchical sub-models: tissue electrophysiology, ToR-ORd-Land model, Courtemanche-Land model, passive mechanics and CircAdapt. For each sub-model, we trained Gaussian processes emulators (GPEs) that were then used to perform a global sensitivity analysis (GSA) to retain parameters explaining 90% of the total sensitivity for subsequent analysis. We identified 45 out of 117 parameters that were important for whole heart function. We performed a GSA over these 45 parameters and identified the systemic and pulmonary peripheral resistance as being critical parameters for a wide range of volumetric and hemodynamic cardiac indexes across all four chambers. We have shown that GPEs provide a robust method for mapping between cellular properties and clinical measurements. This could be applied to identify parameters that can be calibrated in patient-specific models or digital twins, and to link cellular function to clinical indexes.
Date Issued
2023-06
Date Acceptance
2023-06-09
Citation
PLoS Computational Biology, 2023, 19 (6)
ISSN
1553-734X
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Computational Biology
Volume
19
Issue
6
Copyright Statement
Copyright: © 2023 Strocchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:001018392700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Biochemical Research Methods
Biochemistry & Molecular Biology
CALCIUM TRANSIENTS
CONTRACTION
DYSFUNCTION
FAILURE
FORCE
HEMODYNAMICS
HYPERTENSION
Life Sciences & Biomedicine
Mathematical & Computational Biology
MECHANISMS
Science & Technology
SIMULATED ISCHEMIC CONDITIONS
SYSTEMIC VASCULAR-RESISTANCE
Publication Status
Published
Article Number
e1011257
Date Publish Online
2023-06-26