170434 20260422084206.0 doi 10.1371/journal.pcbi.1013740 sideral 148900 ART-2026-148900 eng Rosales, Ricardo M. In silico assessment of arrhythmic risk following the implantation of engineered heart tissues in porcine hearts with varying infarct locations 2026 Access copy available to the general public Unrestricted Engineered heart tissues (EHTs) have shown promise in partially restoring ejection fraction after myocardial infarction (MI); however, their potential to introduce electrophysiological heterogeneities and promote arrhythmias remains underexplored. This study assessed the arrhythmogenic risk following immature EHT engraftment in infarcted ventricles using computational simulations that replicate preclinical protocols. EHT computational models were developed and integrated into nine validated porcine-specific biventricular models from pigs with left circumflex (LCx, n = 4) or left anterior descending (LAD, n = 5) MIs. Ventricular tachycardia (VT) susceptibility was evaluated using an S1–S2 stimulation protocol across varying pacing sites and coupling intervals, accounting for infarct characteristics, implantation site, conductivity, and the ventricular conduction system (CS). VT burden was quantified with a 0–1 inducibility score (IS). In silico reentrant activity qualitatively reproduced the arrhythmic patterns observed experimentally in porcine MI models. VT vulnerability was greater in LAD than in LCx infarcts, consistent with a larger infarct size. Inclusion of the CS modified VT burden by providing conduction shortcuts that either facilitated or suppressed reentry. Remuscularization directly on the MI region (IS = 0.49) heightened VT inducibility in dense, transmural scars (IS = 0.16), whereas lateral EHT implantation (IS = 0.35) reduced this risk with respect to direct implantation. In non-transmural scars, VT inducibility varied with the implantation site. Matching EHT conductivity to host myocardium lowered or contained arrhythmogenicity (LCx-IS: from 0.5 to 0.25; LAD-IS: stable at 0.57). These results highlight the latent arrhythmic risk of EHT-mediated remuscularization after MI, identifying infarct substrate, EHT conductivity, and implantation site as critical determinants, and emphasize the importance of incorporating the CS for accurate risk assessment info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Ríos-Muñoz, Gonzalo R. Sánchez de la Nava, Ana María Fernández-Santos, María Eugenia Bermejo, Javier Doblaré, Manuel Universidad de Zaragoza (orcid)0000-0001-8741-6452 Mincholé, Ana Universidad de Zaragoza (orcid)0000-0003-3183-4107 Pueyo, Esther Universidad de Zaragoza (orcid)0000-0002-1960-407X 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 22, 4 (2026), e1013740 [32 pp.] PLoS Comput. Biol. PLOS COMPUTATIONAL BIOLOGY 1553-734X 3658960 http://zaguan.unizar.es/record/170434/files/texto_completo.pdf Versión publicada 2802676 http://zaguan.unizar.es/record/170434/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:170434 articulos driver 2026-04-22-08:40:12 ARTICLE