{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:37Z","timestamp":1791974137194,"version":"4.4.0"},"reference-count":31,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL142496"],"award-info":[{"award-number":["R01HL142496"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL126802"],"award-info":[{"award-number":["R01HL126802"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL125239"],"award-info":[{"award-number":["HL125239"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1746891"],"award-info":[{"award-number":["DGE-1746891"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,1,7]]},"abstract":"<jats:p>Hypertrophic cardiomyopathy (HCM) is associated with risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VAs) arising from the proliferation of fibrosis in the heart. Current clinical risk stratification criteria inadequately identify at-risk patients in need of primary prevention of VA. Here, we use mechanistic computational modeling of the heart to analyze how HCM-specific remodeling promotes arrhythmogenesis and to develop a personalized strategy to forecast risk of VAs in these patients. We combine contrast-enhanced cardiac magnetic resonance imaging and T1 mapping data to construct digital replicas of HCM patient hearts that represent the patient-specific distribution of focal and diffuse fibrosis and evaluate the substrate propensity to VA. Our analysis indicates that the presence of diffuse fibrosis, which is rarely assessed in these patients, increases arrhythmogenic propensity. In forecasting future VA events in HCM patients, the imaging-based computational heart approach achieved 84.6%, 76.9%, and 80.1% sensitivity, specificity, and accuracy, respectively, and significantly outperformed current clinical risk predictors. This novel VA risk assessment may have the potential to prevent SCD and help deploy primary prevention appropriately in HCM patients.<\/jats:p>","DOI":"10.7554\/elife.73325","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T06:15:28Z","timestamp":1641881728000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73325","source":"Crossref","is-referenced-by-count":43,"title":["Personalized computational heart models with T1-mapped fibrotic remodeling predict sudden death risk in patients with hypertrophic cardiomyopathy"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-1799","authenticated-orcid":true,"given":"Ryan P","family":"O'Hara","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University","place":["Baltimore, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edem","family":"Binka","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Johns Hopkins School of Medicine","place":["Baltimore, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adityo","family":"Prakosa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University","place":["Baltimore, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan L","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Radiology, Johns Hopkins School of Medicine","place":["Baltimore, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Cartoski","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Nemours\/Alfred I. duPont Hospital for Children","place":["Wilmington, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Roselle","family":"Abraham","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of California, San Francisco","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai-Yin","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of California, San Francisco","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-1239","authenticated-orcid":true,"given":"Patrick M","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington","place":["Seattle, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8661-063X","authenticated-orcid":true,"given":"Natalia A","family":"Trayanova","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University","place":["Baltimore, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11437","article-title":"Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models","volume":"7","author":"Arevalo","year":"2016","journal-title":"Nature Communications"},{"key":"bib2","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":"Annals of Biomedical Engineering"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1186\/s12968-020-0603-y","article-title":"Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation","volume":"22","author":"Begg","year":"2020","journal-title":"Journal of Cardiovascular Magnetic Resonance"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1136\/heartjnl-2016-309303","article-title":"Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia","volume":"103","author":"Bui","year":"2017","journal-title":"Heart"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1007\/s00246-019-02082-7","article-title":"Computational Identification of Ventricular Arrhythmia Risk in Pediatric Myocarditis","volume":"40","author":"Cartoski","year":"2019","journal-title":"Pediatric Cardiology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1097\/RCT.0000000000000564","article-title":"Structural and Functional Correlates of Myocardial T1 Mapping in 321 Patients With Hypertrophic Cardiomyopathy","volume":"41","author":"Chu","year":"2017","journal-title":"Journal of Computer Assisted Tomography"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1161\/CIRCULATIONAHA.112.134932","article-title":"Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy","volume":"127","author":"Coppini","year":"2013","journal-title":"Circulation"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1186\/1532-429X-14-76","article-title":"Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction","volume":"14","author":"Ellims","year":"2012","journal-title":"Journal of Cardiovascular Magnetic Resonance"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1093\/ehjci\/jeu077","article-title":"A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype","volume":"15","author":"Ellims","year":"2014","journal-title":"European Heart Journal. Cardiovascular Imaging"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003090","article-title":"Histological and Histometric Characterization of Myocardial Fibrosis in End-Stage Hypertrophic Cardiomyopathy: A Clinical-Pathological Study of 30 Explanted Hearts","volume":"9","author":"Galati","year":"2016","journal-title":"Circulation. Heart Failure"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"e212","DOI":"10.1016\/j.jacc.2011.06.011","article-title":"2011 ACCF\/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons","volume":"58","author":"Gersh","year":"2011","journal-title":"Journal of the American College of Cardiology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1016\/j.jacc.2008.06.049","article-title":"Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping","volume":"52","author":"Iles","year":"2008","journal-title":"Journal of the American College of Cardiology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.amjcard.2004.01.057","article-title":"Long-term follow-up of implantable cardioverter defibrillator therapy for hypertrophic cardiomyopathy","volume":"93","author":"Jayatilleke","year":"2004","journal-title":"The American Journal of Cardiology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.hrthm.2016.01.001","article-title":"Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts","volume":"13","author":"Lambiase","year":"2016","journal-title":"Heart Rhythm"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.amjmed.2003.10.012","article-title":"Hypertrophic cardiomyopathy: an important global disease","volume":"116","author":"Maron","year":"2004","journal-title":"The American Journal of Medicine"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.jacc.2010.11.013","article-title":"Assessment of myocardial fibrosis with cardiovascular magnetic resonance","volume":"57","author":"Mewton","year":"2011","journal-title":"Journal of the American College of Cardiology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1002\/jmri.25811","article-title":"Increased myocardial native T1 relaxation time in patients with nonischemic dilated cardiomyopathy with complex ventricular arrhythmia","volume":"47","author":"Nakamori","year":"2018","journal-title":"Journal of Magnetic Resonance Imaging"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1161\/CIRCHEARTFAILURE.112.967026","article-title":"Patterns of disease progression in hypertrophic cardiomyopathy: an individualized approach to clinical staging","volume":"5","author":"Olivotto","year":"2012","journal-title":"Circulation. Heart Failure"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002061","article-title":"Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation","volume":"7","author":"O\u2019Hara","year":"2011","journal-title":"PLOS Computational Biology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1093\/eurheartj\/eht439","article-title":"A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD)","volume":"35","author":"O\u2019Mahony","year":"2014","journal-title":"European Heart Journal"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"3381","DOI":"10.1098\/rsta.2008.0112","article-title":"From mitochondrial ion channels to arrhythmias in the heart: computational techniques to bridge the spatio-temporal scales","volume":"366","author":"Plank","year":"2008","journal-title":"Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.pbiomolbio.2014.08.009","article-title":"Methodology for image-based reconstruction of ventricular geometry for patient-specific modeling of cardiac electrophysiology","volume":"115","author":"Prakosa","year":"2014","journal-title":"Progress in Biophysics and Molecular Biology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41551-018-0282-2","article-title":"Personalized virtual-heart technology for guiding the ablation of infarct-related ventricular tachycardia","volume":"2","author":"Prakosa","year":"2018","journal-title":"Nature Biomedical Engineering"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1109\/TBME.2009.2014243","article-title":"Automatically generated, anatomically accurate meshes for cardiac electrophysiology problems","volume":"56","author":"Prassl","year":"2009","journal-title":"IEEE Transactions on Bio-Medical Engineering"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2021.104674","article-title":"Electromechanical modeling of human ventricles with ischemic cardiomyopathy: numerical simulations in sinus rhythm and under arrhythmia","volume":"136","author":"Salvador","year":"2021","journal-title":"Computers in Biology and Medicine"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/CIRCHEARTFAILURE.112.969626","article-title":"Outcome and complications after implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: systematic review and meta-analysis","volume":"5","author":"Schinkel","year":"2012","journal-title":"Circulation. Heart Failure"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.119.008213","article-title":"Preprocedure Application of Machine Learning and Mechanistic Simulations Predicts Likelihood of Paroxysmal Atrial Fibrillation Recurrence Following Pulmonary Vein Isolation","volume":"13","author":"Shade","year":"2020","journal-title":"Circulation. Arrhythmia and Electrophysiology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.hrthm.2019.10.002","article-title":"Ventricular arrhythmia risk prediction in repaired Tetralogy of Fallot using personalized computational cardiac models","volume":"17","author":"Shade","year":"2020","journal-title":"Heart Rhythm"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi8020","article-title":"Predicting risk of sudden cardiac death in patients with cardiac sarcoidosis using multimodality imaging and personalized heart modeling in a multivariable classifier","volume":"7","author":"Shade","year":"2021","journal-title":"Science Advances"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"H1088","DOI":"10.1152\/ajpheart.00109.2006","article-title":"Alternans and spiral breakup in a human ventricular tissue model","volume":"291","author":"ten Tusscher","year":"2006","journal-title":"American Journal of Physiology. Heart and Circulatory Physiology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.pbiomolbio.2007.07.012","article-title":"Solvers for the cardiac bidomain equations","volume":"96","author":"Vigmond","year":"2008","journal-title":"Progress in Biophysics and Molecular Biology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/73325\/elife-73325-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/73325\/elife-73325-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/73325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:08:13Z","timestamp":1697058493000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/73325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,25]]},"references-count":31,"alternative-id":["10.7554\/eLife.73325"],"URL":"https:\/\/doi.org\/10.7554\/elife.73325","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.10.04.21264520","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2021.10.04.21264520","asserted-by":"object"}],"is-supplemented-by":[{"id-type":"doi","id":"10.5061\/dryad.bk3j9kdd0","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.73325.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.73325.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,25]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e73325"}}