doi:10.1371/journal.pcbi.1013688engRosales, Ricardo M.Wu, MingClaus, PietJanssens, StefanRíos-Muñoz, Gonzalo R.Fernández-Santos, María EugeniaMartínez-Legazpi, PabloBermejo, JavierFlanagan, AidenDoblaré, ManuelMincholé, AnaPueyo, EstherIntegrated multi-modal data analysis for computational modeling of healthy and location-dependent myocardial infarction conditions in porcine heartsART-2026-148722Porcine hearts are widely used for preclinical cardiac evaluation. Computational models, by effectively integrating comprehensive experimental data, often reinforce this preclinical assessment. Using extensive multi-modal data, we developed swine ventricular digital twins for healthy and chronic myocardial infarction (MI) conditions to investigate the roles of the cardiac conduction system (CS), spatial repolarization heterogeneities, cardiomyocyte orientation, cell-to-cell coupling, and MI characteristics on ventricular function. We analyzed cardiac magnetic resonance (CMR) images, electrocardiograms (ECGs), and optical (OM) and electroanatomical mapping from 5 healthy and 10 MI pigs. CS architectures were built from OM and ECG recordings. Myocardial fiber orientation, action potential characteristics, and cell-to-cell conductivity in MI tissue were defined from OM and CMR data. Simulated ECGs for healthy and MI models of left anterior descending and left circumflex occlusions were compared to experimental ECGs and were used to assess MI-induced changes. Subject-specific fiber orientation calibration minimally affected electrophysiology, with conduction velocity (CV) and action potential duration (APD) changing by less than 3.6% with respect to standard orientation. Accurate CS and repolarization heterogeneities reproduced depolarization (Pearson correlation 0.76 for QRS) and repolarization (Pearson correlation 0.74 for T-wave) patterns. Incorporating experimentally guided MI-induced alterations enabled the replication of MI depolarization and repolarization features (relative errors: 0.5% CV, 2.9% APD), yielded realistic T-wave morphologies (0.63 Pearson correlation), and revealed ECG patterns specific to vessel-dependent occlusions. Thus, by integrating extensive multi-modal data, we advance porcine cardiac digital twins and demonstrate the influence of key structural and electrophysiological parameters on healthy and MI heart function, providing a robust computational framework for mechanistic and translational applications.2026http://zaguan.unizar.es/record/17023210.1371/journal.pcbi.1013688http://zaguan.unizar.es/record/170232oai:zaguan.unizar.es:170232info:eu-repo/grantAgreement/ES/AEI/PID2023-148975OB-I00info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-23R-BSICoSinfo:eu-repo/grantAgreement/ES/MCIN/PLEC2021-008127info:eu-repo/grantAgreement/ES/MICINN/CNS2022-135899info:eu-repo/grantAgreement/ES/MICINN/PID2022-140556OB-I00info:eu-repo/grantAgreement/EUR/MICINN/TED2021-130459B-I00PLOS COMPUTATIONAL BIOLOGY 22, 3 (2026), e1013688 [38 pp.]byhttps://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccess