{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:11:32Z","timestamp":1775841092119,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated multi-scale, multi-physics computational human heart model was adapted to the patient-specific geometry, yielding a model consisting of 91,000 solid elements. This model was coupled to a virtual circulatory system and calibrated to clinically measured parameters from echocardiography and cardiac catheterization data. The simulation replicated key physiologic parameters within 10% of their clinically measured values. Global LV systolic myocardial stress was 7.1 \u00b1 1.8\u00a0kPa. Mean stress of the basal, middle, and apical segments were 7.7 \u00b1 1.8\u00a0kPa, 9.1 \u00b1 3.8\u00a0kPa, and 6.4 \u00b1 0.4\u00a0kPa, respectively. This is the first patient-specific computational model of LFLG AS based on clinical imaging. Low myocardial stress correlated with low ejection fraction and eccentric LV remodeling. Further studies are needed to understand how alterations in LV biomechanics correlates with clinical outcomes of AS.<\/jats:p>","DOI":"10.3389\/fphys.2022.848011","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:19:05Z","timestamp":1649225945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Left Ventricle Biomechanics of Low-Flow, Low-Gradient Aortic Stenosis: A Patient-Specific Computational Model"],"prefix":"10.3389","volume":"13","author":[{"given":"Andrew D.","family":"Wisneski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Cutugno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Pasta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Stroh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom C.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaikom S.","family":"Mahadevan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julius M.","family":"Guccione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1161\/circimaging.111.967554","article-title":"Low-flow, Low-Gradient Severe Aortic Stenosis Despite normal Ejection Fraction Is Associated with Severe Left Ventricular Dysfunction as Assessed by Speckle-Tracking Echocardiography: a Multicenter Study","volume":"5","author":"Adda","year":"2012","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"B2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.euromechsol.2014.04.001","article-title":"The Living Heart Project: A Robust and Integrative Simulator for Human Heart Function","volume":"48","author":"Baillargeon","year":"2014","journal-title":"Eur. J. Mech. A. Sol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1007\/s10439-012-0593-5","article-title":"A Novel Rule-Based Algorithm for Assigning Myocardial Fiber Orientation to Computational Heart Models","volume":"40","author":"Bayer","year":"2012","journal-title":"Ann. Biomed. Eng."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1016\/j.athoracsur.2012.03.001","article-title":"Patient-specific Finite Element-Based Analysis of Ventricular Myofiber Stress after Coapsys: Importance of Residual Stress","volume":"93","author":"Carrick","year":"2012","journal-title":"Ann. Thorac. Surg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1067\/mnc.2002.123122","article-title":"Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart. A Statement for Healthcare Professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association","volume":"9","author":"Cerqueira","year":"2002","journal-title":"Circulation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1093\/eurheartj\/ehw096","article-title":"Low-gradient Aortic Stenosis","volume":"37","author":"Clavel","year":"2016","journal-title":"Eur. Heart J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.3389\/fphys.2018.01003","article-title":"Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype with Preserved Ejection Fraction","volume":"9","author":"Dabiri","year":"2018","journal-title":"Front. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1152\/japplphysiol.00255.2014","article-title":"Distribution of normal Human Left Ventricular Myofiber Stress at End Diastole and End Systole: a Target for In Silico Design of Heart Failure Treatments","volume":"117","author":"Genet","year":"2014","journal-title":"J. Apply. Physiol. 1985"},{"key":"B10","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s10439-015-1351-2","article-title":"Modeling Pathologies of Diastolic and Systolic Heart Failure","volume":"44","author":"Genet","year":"2016","journal-title":"Ann. Biomed. Eng."},{"key":"B11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1115\/1.2895473","article-title":"Mechanics of Active Contraction in Cardiac Muscle: Part I-Constitutive Relations for Fiber Stress that Describe Deactivation","volume":"115","author":"Guccione","year":"1993","journal-title":"J. Biomech. Eng."},{"key":"B12","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1115\/1.2895474","article-title":"Mechanics of Active Contraction in Cardiac Muscle: Part II-Cylindrical Models of the Systolic Left Ventricle","volume":"115","author":"Guccione","year":"1993","journal-title":"J. Biomech. Eng."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1161\/circulationaha.106.668681","article-title":"Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Preserved Ejection Fraction Is Associated with Higher Afterload and Reduced Survival","volume":"115","author":"Hachicha","year":"2007","journal-title":"Circulation"},{"key":"B14","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.jacc.2011.02.059","article-title":"Low-gradient Aortic Valve Stenosis Myocardial Fibrosis and its Influence on Function and Outcome","volume":"58","author":"Herrmann","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1098\/rsta.2009.0091","article-title":"Constitutive Modelling of Passive Myocardium: a Structurally Based Framework for Material Characterization","volume":"367","author":"Holzapfel","year":"2009","journal-title":"Philos. Trans. A. Math. Phys. Eng. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1002\/ejhf.1436","article-title":"The Role of Ventricular-Arterial Coupling in Cardiac Disease and Heart Failure: Assessment, Clinical Implications and Therapeutic Interventions. A Consensus Document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association","volume":"21","author":"Ikonomidis","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"B17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1152\/japplphysiol.00662.2012","article-title":"Analysis of Patient-specific Surgical Ventricular Restoration: Importance of an Ellipsoidal Left Ventricular Geometry for Diastolic and Systolic Function","volume":"115","author":"Lee","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1161\/circresaha.111.300084","article-title":"Current Management of Calcific Aortic Stenosis","volume":"113","author":"Lindman","year":"2013","journal-title":"Circ. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1002\/mrm.28724","article-title":"Myofiber Strain in Healthy Humans Using DENSE and cDTI","volume":"86","author":"Moulin","year":"2021","journal-title":"Magn. Reson. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e521","DOI":"10.1161\/CIR.0000000000000031","article-title":"2014 AHA\/ACC Guideline for the Management of Patients with Valvular Heart Disease: a Report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"Nishimura","year":"2014","journal-title":"Circulation"},{"key":"B21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jacc.2014.10.030","article-title":"Management of Paradoxical Low-Flow, Low-Gradient Aortic Stenosis: Need for an Integrated Approach, Including Assessment of Symptoms, Hypertension, and Stenosis Severity","volume":"65","author":"Pibarot","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1016\/j.jacc.2012.06.051","article-title":"Low-flow, Low-Gradient Aortic Stenosis with normal and Depressed Left Ventricular Ejection Fraction","volume":"60","author":"Pibarot","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.actbio.2020.04.033","article-title":"Intra-myocardial Alginate Hydrogel Injection Acts as a Left Ventricular Mid-wall Constraint in Swine","volume":"111","author":"Sack","year":"2020","journal-title":"Acta Biomater."},{"key":"B24","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3389\/fphys.2018.00539","article-title":"Construction and Validation of Subject-Specific Biventricular Finite-Element Models of Healthy and Failing Swine Hearts from High-Resolution DT-MRI","volume":"9","author":"Sack","year":"2018","journal-title":"Front. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"421","DOI":"10.5301\/ijao.5000520","article-title":"Partial LVAD Restores Ventricular Outputs and Normalizes LV but Not RV Stress Distributions in the Acutely Failing Heart In Silico","volume":"39","author":"Sack","year":"2016","journal-title":"Int. J. Artif. Organs"},{"key":"B26","doi-asserted-by":"publisher","first-page":"520","DOI":"10.3389\/fphys.2018.00520","article-title":"Investigating the Role of Interventricular Interdependence in Development of Right Heart Dysfunction During LVAD Support: A Patient-Specific Methods-Based Approach","volume":"9","author":"Sack","year":"2018","journal-title":"Front. Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"10130","DOI":"10.1007\/s12265-021-10130-y","article-title":"Computational Modeling Studies of the Roles of Left Ventricular Geometry, Afterload, and Muscle Contractility on Myocardial Strains in Heart Failure with Preserved Ejection Fraction","volume":"14","author":"Shavik","year":"2021","journal-title":"J. Cardiovasc. Transl Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"H692","DOI":"10.1152\/ajpheart.01226.2004","article-title":"MRI-based Finite-Element Analysis of Left Ventricular Aneurysm","volume":"289","author":"Walker","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/j.athoracsur.2011.12.066","article-title":"First Evidence of Depressed Contractility in the Border Zone of a Human Myocardial Infarction","volume":"93","author":"Wenk","year":"2012","journal-title":"Ann. Thorac. Surg."},{"key":"B30","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/978-3-030-78710-3_36","article-title":"From Clinical Imaging to Patient-Specific Computational Model: Rapid Adaptation of the Living Heart Human Model to a Case of Aortic Stenosis","volume":"12738","author":"Wisneski","year":"2021","journal-title":"Lecture Notes Comp. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"574211","DOI":"10.3389\/fphys.2020.574211","article-title":"Impact of Aortic Stenosis on Myofiber Stress: Translational Application of Left Ventricle-Aortic Coupling Simulation","volume":"11","author":"Wisneski","year":"2020","journal-title":"Front. Physiol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.848011\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:19:07Z","timestamp":1649225947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.848011\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":30,"alternative-id":["10.3389\/fphys.2022.848011"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.848011","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]},"article-number":"848011"}}