Ventricular anatomical complexity and sex differences impact predictions from electrophysiological computational models

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• dc.contributor.author Gonzalez Martin, Pablo
• dc.contributor.author Sacco, Federica
• dc.contributor.author Butakoff, Constantine
• dc.contributor.author Doste Beltrán, Rubén
• dc.contributor.author Bederian, Carlos
• dc.contributor.author Gutierrez Espinosa de los Monteros, Lilian K.
• dc.contributor.author Houzeaux, Guillaume
• dc.contributor.author Iaizzo, Paul A.
• dc.contributor.author Iles, Tinen L.
• dc.contributor.author Vázquez, Mariano
• dc.contributor.author Aguado-Sierra, Jazmin
• dc.date.accessioned 2023-06-20T06:20:08Z
• dc.date.available 2023-06-20T06:20:08Z
• dc.date.issued 2023
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O’Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies.
• dc.description.sponsorship JA-S, FS, GH and MV are supported by the European Union’s Horizon 2020 research and innovation programme under grant agreements No 675451 (Compbiomed project phase 1) and No 823712 (CompBioMed project, phase 2) and project No 777204 (SilicoFCM project). Part of the simulation computing hours were provided by the CompBioMed project phase 1. JA-S was awarded computation time from Red Espanola de Supercomputacion (RES). (Activity IDs: FI-2018-2-0049 and BCV-2019-2-0014) JA-S is funded by a Ramon y Cajal fellowship (RYC-2017-22532), Ministerio de Ciencia e Innovacion, Spain; and by Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2017-2020 from the Ministerio de Ciencia e Innovacion y Universidades (PID2019-104356RBC41/AEI/10.13039/501100011033): meHeart ME PID2019-104356RB-C44. CB is funded by the Torres Quevedo Program (PTQ2018-010290), Ministerio de Ciencia e Innovacion, Spain. MV, GH and CB are funded by the Spanish Neotec project EXP - 00123159/SNEO-20191113 Generador de corazones virtuales. LKGM was funded by Fundacion Carolina-BBVA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.
• dc.format.mimetype application/pdf
• dc.identifier.citation Gonzalez-Martin P, Sacco F, Butakoff C, Doste R, Bederian C, Gutierrez LK, et al. Ventricular anatomical complexity and sex differences impact predictions from electrophysiological computational models. PLoS ONE. 2023 Feb 13;18(2):e0263639. DOI: 10.1371/journal.pone.0263639
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0263639
• dc.identifier.issn 1932-6203
• dc.identifier.uri http://hdl.handle.net/10230/57242
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS ONE. 2023 Feb 13;18(2):e0263639
• dc.relation.isreferencedby https://doi.org/10.1371/journal.pone.0263639.s001
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/675451
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/823712
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/777204
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-104356RB-C41
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-104356RB-C44
• dc.rights © 2023 Gonzalez-Martin 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Electrofisiologia
• dc.subject.other Endocardi
• dc.subject.other Ressonància magnètica
• dc.subject.other Cor -- Ventricles
• dc.title Ventricular anatomical complexity and sex differences impact predictions from electrophysiological computational models
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion