{ "abstract": "A major challenge in computational models of cardiac electromechanics is the reconstruction of myocardial fiber architecture, as direct in vivo measurements of fiber orientation are not feasible. Consequently, rule-based methods are commonly adopted as surrogates, relying on empirical descriptions of fiber organization combined with patient-specific geometries. This study investigates the respective roles of macroscopic fiber architecture and microscopic fiber disarray in cardiac electromechanical simulations. A high-fidelity biventricular electromechanical model of a murine heart was developed using a high-resolution myocardial fiber field obtained via mesoscopic optical imaging, which serves as a reference ground truth. A spatial smoothing strategy is introduced to decouple macroscopic fiber organization from local disarray, and the resulting responses are also compared with those obtained using a rule-based fiber field. The results show that passive mechanics and electrophysiological activation are only weakly affected by fiber disarray, with global chamber compliance and activation times remaining largely unchanged across different fiber descriptions. In contrast, active mechanics is highly sensitive to fiber architecture. Moderate regularization of the experimentally measured fiber field enhances the ventricular pumping efficiency of the computational model by reducing microscopic disarray while preserving the macroscopic helical organization, whereas excessive smoothing or rule-based fiber reconstructions lead to unphysiologically strong or inefficient contraction. Within this framework, two commonly adopted surrogate strategies to account for fiber disarray are investigated: (i) a reduction of the effective cross-bridge stiffness in the active tension model, and (ii) the introduction of controlled misalignment between active tension and the local fiber direction. While both approaches reproduce global hemodynamic indicators comparable to the reference case, an effective reduction of contractility – despite its phenomenological nature – provides a closer match to the reference strain patterns than the introduction of orthogonal active stress components. Overall, the results highlight the dominant role of macroscopic fiber architecture in active mechanics and reveal important limitations of commonly adopted surrogate approaches for modeling fiber disarray. Author summary: To integrate cardiac computational models into routine clinical practice, it is essential to validate the modeling strategies proposed in the scientific literature. A major challenge in this context is the reconstruction of myocardial fiber fields, as obtaining precise in-vivo measurements of fiber orientation within patient-specific organs remains infeasible. An additional source of complexity arises from fiber disarray, which refers to local deviations of fiber orientation from the average direction.", "abstract_shown": true, "affiliations": [ "MOX - Department of Mathematics, Politecnico di Milano, Milan, Italy", "Department of Theoretical and Applied Sciences, eCampus University, Novedrate, Italy", "SMARTEST Research Center, eCampus University, Novedrate, Italy", "Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg – Bad Krozingen, Medical Faculty and Medical Center – University of Freiburg, Freiburg im Breisgau, Germany", "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy", "Institute of Clinical Physiology, National Research Council (IFC-CNR), Florence, Italy" ], "article_type": "Research Article", "arxiv": null, "author_total": 8, "authors": [ { "affs": [ 0 ], "name": "Carlo Guastamacchia" }, { "affs": [ 1 ], "name": "Roberto Piersanti" }, { "affs": [ 2 ], "name": "Francesco Giardini" }, { "affs": [ 3 ], "name": "Raffaele Coppini" }, { "affs": [ 4 ], "name": "Cecilia Ferrantini" }, { "affs": [ 5 ], "name": "Luca Dede’" }, { "name": "Leonardo Sacconi" }, { "name": "Francesco Regazzoni" } ], "bibtex": "https://research.draconitic.com/paper/aszkzq3tx8mv8.bib", "cited_by": 0, "doi": "10.1371/journal.pcbi.1014807", "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014807", "id": "aszkzq3tx8mv8", "issns": [ "1553-7358" ], "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014807", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2705|Cardiac electrophysiology and arrhythmias" ], [ "plos", "/Biology and life sciences/Anatomy/Cardiovascular anatomy/Heart" ], [ "plos", "/Biology and life sciences/Anatomy/Cardiovascular anatomy/Heart/Endocardium" ], [ "plos", "/Biology and life sciences/Anatomy/Cardiovascular anatomy/Heart/Epicardium" ], [ "plos", "/Biology and life sciences/Anatomy/Cardiovascular anatomy/Heart/Myocardium" ], [ "plos", "/Biology and life sciences/Anatomy/Musculoskeletal system/Muscles/Muscle fibers/Cardiac muscle fibers" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Muscle fibers/Cardiac muscle fibers" ], [ "plos", "/Biology and life sciences/Physiology/Electrophysiology" ], [ "plos", "/Biology and life sciences/Physiology/Muscle physiology/Muscle contraction" ], [ "plos", "/Medicine and health sciences/Anatomy/Cardiovascular anatomy/Heart" ], [ "plos", "/Medicine and health sciences/Anatomy/Cardiovascular anatomy/Heart/Endocardium" ], [ "plos", "/Medicine and health sciences/Anatomy/Cardiovascular anatomy/Heart/Epicardium" ], [ "plos", "/Medicine and health sciences/Anatomy/Cardiovascular anatomy/Heart/Myocardium" ], [ "plos", "/Medicine and health sciences/Anatomy/Musculoskeletal system/Muscles/Muscle fibers/Cardiac muscle fibers" ], [ "plos", "/Physical sciences/Physics/Classical mechanics/Damage mechanics/Deformation" ], [ "plos", "/Physical sciences/Physics/Classical mechanics/Deformation" ] ], "openalex": "W7148537387", "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014807&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-21", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/aszkzq3tx8mv8.ris", "sources": [ { "first_seen": "2026-10-30T12:17:43Z", "native_id": "10.1371/journal.pcbi.1014807", "source": "plos", "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014807" } ], "subjects": [ { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "The functional impact of myofiber macroscopic organization and disarray in computational models of the murine heart", "title_text": "The functional impact of myofiber macroscopic organization and disarray in computational models of the murine heart", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:43Z", "url": "https://research.draconitic.com/paper/aszkzq3tx8mv8", "venue": "PLOS Computational Biology", "versions": [] }