{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:37:49Z","timestamp":1788327469551,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"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>In patients with healed myocardial infarction, the left ventricular ejection fraction is characterized by low sensitivity and specificity in the prediction of future malignant arrhythmias. Thus, there is the need for new parameters in daily practice to perform arrhythmic risk stratification. The aim of this study is to identify some features of proarrhythmic geometric configurations of scars and border zones (BZ), by means of numerical simulations based on left ventricular models derived from post myocardial infarction patients. Two patients with similar clinical characteristics were included in this study. Both patients exhibited left ventricular scars characterized by subendo- and subepicardial BZ and a transmural BZ isthmus. The scar of patient #1 was significantly larger than that of patient #2, whereas the transmural BZ isthmus and the subdendo- and subepicardial BZs of patient #2 were thicker than those of patient #1. Patient #1 was positive at electrophysiologic testing, whereas patient #2 was negative. Based on the cardiac magnetic resonance (CMR) data, we developed a geometric model of the left ventricles of the two patients, taking into account the position, extent, and topological features of scars and BZ. The numerical simulations were based on the anisotropic monodomain model of electrocardiology. In the model of patient #1, sustained ventricular tachycardia (VT) was inducible by an S2 stimulus delivered at any of the six stimulation sites considered, while in the model of patient #2 we were not able to induce sustained VT. In the model of patient #1, making the subendo- and subepicardial BZs as thick as those of patient #2 did not affect the inducibility and maintenance of VT. On the other hand, in the model of patient #2, making the subendo- and subepicardial BZs as thin as those of patient #1 yielded sustained VT. In conclusion, the results show that the numerical simulations have an effective predictive capability in discriminating patients at high arrhythmic risk. The extent of the infarct scar and the presence of transmural BZ isthmuses and thin subendo- and subepicardial BZs promote sustained VT.<\/jats:p>","DOI":"10.3389\/fphys.2022.834747","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T10:22:09Z","timestamp":1648549329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of Scar and Border Zone Geometry on the Genesis and Maintenance of Re-Entrant Ventricular Tachycardia in Patients With Previous Myocardial Infarction"],"prefix":"10.3389","volume":"13","author":[{"given":"Vincenzo","family":"Gionti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Scacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Colli Franzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca F.","family":"Pavarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Dore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Storti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"B1","first-page":"e272","article-title":"2017 AHA\/ACC\/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death","author":"Al-Khatib","year":"2018"},{"key":"B2","first-page":"2383","article-title":"Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model","author":"Amado","year":"2004"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11437","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":"Nat. Commun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/j.hrthm.2013.04.015","article-title":"Feasibility of image-based simulation to estimate ablation target in human ventricular arrhythmia","volume":"10","author":"Ashikaga","year":"2013","journal-title":"Heart Rhythm."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1161\/CIRCULATIONAHA.105.534784","article-title":"Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia","volume":"112","author":"Baba","year":"2005","journal-title":"Circulation."},{"key":"B6","unstructured":"BalayS.\n            AbhyankarS.\n            AdamsM. A.\n            BrownJ.\n            BruneP.\n            BuschelmanK.\n          PETSc Users Manual2020"},{"key":"B7","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3389\/fphys.2014.00483","article-title":"Dynamics of propagation of premature impulses in structurally remodeled infarcted myocardium: a computational analysis","volume":"5","author":"Cabo","year":"2014","journal-title":"Front. Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"H372","DOI":"10.1152\/ajpheart.00512.2002","article-title":"Electrical remodeling of the epicardial border zone in the canine infarcted heart: a computational analysis","volume":"284","author":"Cabo","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.cardiores.2006.07.005","article-title":"Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct","volume":"72","author":"Cabo","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"104214","DOI":"10.1016\/j.compbiomed.2021.104214","article-title":"Assessing the ability of substrate mapping techniques to guide ventricular tachycardia ablation using computational modelling","volume":"130","author":"Campos","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3389\/fphy.2018.00057","article-title":"Microscopic isthmuses and fibrosis within the border zone of infarcted hearts promote calcium-mediated ectopy and conduction block","volume":"6","author":"Campos","year":"2018","journal-title":"Front. Phys."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.hrthm.2007.04.015","article-title":"Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping","volume":"4","author":"Ciaccio","year":"2007","journal-title":"Heart Rhythm."},{"key":"B13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1046\/j.1540-8167.2004.03134.x","article-title":"Localization of the isthmus in reentrant circuits by analysis of electrograms derived from clinical noncontact mapping during sinus rhythm and ventricular tachycardia","volume":"15","author":"Ciaccio","year":"2004","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.compbiomed.2015.04.032","article-title":"Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts","volume":"62","author":"Ciaccio","year":"2015","journal-title":"Comput. Biol. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.jacc.2008.05.038","article-title":"Electroanatomic characterization of post-infarct scars","volume":"52","author":"Codreanu","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"108228","DOI":"10.1016\/j.mbs.2019.108228","article-title":"Role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry","volume":"315","author":"Colli-Franzone","year":"2019","journal-title":"Math. Biosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0025-5564(90)90020-Y","article-title":"Mathematical modeling of the excitation process in myocardial tissue: influence of fiber rotation on wavefront propagation and potential field","volume":"101","author":"Colli-Franzone","year":"1990","journal-title":"Math. Biosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.mbs.2011.02.002","article-title":"Exploring anodal and cathodal make and break cardiac excitation mechanisms in a 3d anisotropic bidomain model","volume":"230","author":"Colli-Franzone","year":"2011","journal-title":"Math. Biosci."},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-04801-7","volume-title":"Mathematical Cardiac Electrophysiology.","author":"Colli-Franzone","year":"2014"},{"key":"B20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.mbs.2005.04.003","article-title":"Simulating patterns of excitation, repolarization and action potential duration with cardiac bidomain and monodomain models","volume":"197","author":"Colli-Franzone","year":"2005","journal-title":"Math. Biosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1109\/TBME.2015.2421296","article-title":"Local gradients in electrotonic loading modulate the local effective refractory period: Implications for arrhythmogenesis in the infarct border zone","volume":"62","author":"Connolly","year":"2015","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4137\/CMC.S39708","article-title":"Computational representations of myocardial infarct scars and implications for arrhythmogenesis","author":"Connolly","year":"2016","journal-title":"Clin. Med. Insights Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.hrthm.2005.03.022","article-title":"Three-dimensional anatomic structure as substrate for ventricular tachycardia\/ventricular fibrillation","volume":"2","author":"de Bakker","year":"2005","journal-title":"Heart Rhythm"},{"key":"B24","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1097\/FJC.0b013e318207a35f","article-title":"Fibrosis and cardiac arrhythmias","volume":"57","author":"de Jong","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"H1588","DOI":"10.1152\/ajpheart.00362.2010","article-title":"Ionic mechanisms of electrophysiological heterogeneity and conduction block in the infarct border zone","volume":"299","author":"Decker","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"282","DOI":"10.3389\/fphys.2015.00282","article-title":"Accuracy of prediction of infarct-related arrhythmic circuits from image-based models reconstructed from low and high resolution MRI","volume":"6","author":"Deng","year":"2015","journal-title":"Front. Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"iv60","DOI":"10.1093\/europace\/euw351","article-title":"A feasibility study of arrhythmia risk prediction in patients with myocardial infarction and preserved ejection fraction","volume":"18","author":"Deng","year":"2016","journal-title":"Europace"},{"key":"B28","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1161\/01.RES.63.1.182","article-title":"Influences of anisotropic tissue structure on reentrant circuits in the epicardial border zone of subacute canine infarcts","volume":"63","author":"Dillon","year":"1988","journal-title":"Circ. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1161\/01.cir.68.3.518","article-title":"Recurrent sustained ventricular tachycardia: structure and ultrastructure of subendocardial regions in which tachycardia originates","volume":"68","author":"Fenoglio","year":"1983","journal-title":"Circulation"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1161\/CIRCULATIONAHA.110.976092","article-title":"Sudden cardiac death prediction and prevention: report from a national heart, lung, and blood institute and heart rhythm society workshop","volume":"122","author":"Fishman","year":"2010","journal-title":"Circulation."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1093\/eurheartj\/ehz260","article-title":"Arrhythmic risk stratification in post myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study","volume":"40","author":"Gatzoulis","year":"2019","journal-title":"Europ. Heart J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/s0195-668x(03)00191-x","article-title":"Out-of-hospital cardiac arrest-the relevance of heart failure. the maastricht circulatory arrest registry","volume":"24","author":"Gorgels","year":"2003","journal-title":"Eur. Heart J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1152\/physrev.1989.69.4.1049","article-title":"Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction","volume":"69","author":"Janse","year":"1989","journal-title":"Physiol. Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/s0008-6363(00)00159-0","article-title":"Delayed rectifier k currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle","volume":"48","author":"Jiang","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1056\/NEJM200011163432003","article-title":"The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction","volume":"343","author":"Kim","year":"2000","journal-title":"New Engl. J. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1016\/j.bpj.2011.08.009","article-title":"Susceptibility to arrhythmia in the infarcted heart depends on myofibroblast density","volume":"101","author":"McDowell","year":"2011","journal-title":"Biophys. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"356","DOI":"10.3389\/fphys.2018.00356","article-title":"Modeling the electrophysiological properties of the infarct border zone","volume":"9","author":"Mendonca Costa","year":"2018","journal-title":"Front. Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/s0003-4975(10)63001-9","article-title":"Extended endocardial resection for the treatment of ventricular tachycardia and ventricular fibrillation","volume":"34","author":"Moran","year":"1982","journal-title":"Ann. Thor. Surg."},{"key":"B39","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1152\/physrev.00014.2006","article-title":"Arrhythmogenic ion-channel remodeling in the heart: Heart failure, myocardial infarction, and atrial fibrillation","volume":"87","author":"Nattel","year":"2007","journal-title":"Physiol. Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"21111","DOI":"10.1038\/s41598-021-00606-x","article-title":"Multiparametric analysis of geometric features of fibrotic textures leading to cardiac arrhythmias","volume":"11","author":"Nezlobinsky","year":"2021","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.rcl.2014.11.005","article-title":"Tissue characterization of the myocardium","volume":"53","author":"Pattanayak","year":"2015"},{"key":"B42","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1161\/01.CIR.95.4.988","article-title":"Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia","volume":"95","author":"Peters","year":"1997","journal-title":"Circulation"},{"key":"B43","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1161\/01.CIR.97.17.1746","article-title":"Myocardial architecture and ventricular arrhythmogenesis","volume":"97","author":"Peters","year":"1998","journal-title":"Circulation"},{"key":"B44","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0008-6363(99)00013-9","article-title":"Electrical remodeling in ischemia and infarction","volume":"42","author":"Pinto","year":"1999","journal-title":"Cardiovasc. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1093\/eurheartj\/ehv316","article-title":"2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"36","author":"Priori","year":"2015","journal-title":"Eur. Heart J."},{"key":"B46","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1114\/1.1581877","article-title":"Spatial methods of epicardial activation time determination in normal hearts","volume":"31","author":"Punske","year":"2003","journal-title":"Ann. Biomed. Eng."},{"key":"B47","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1148\/radiology.156.3.4023232","article-title":"Left ventricular volumes measured by MR imaging","volume":"156","author":"Rehr","year":"1985","journal-title":"Radiology."},{"key":"B48","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1161\/01.res.44.5.701","article-title":"Influence of cardiac fiber orientation on wavefront voltage, conduction velocity, and tissue resistivity in the dog. Circ","volume":"44","author":"Roberts","year":"1979"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1016\/j.hrthm.2015.08.020","article-title":"Contemporary rates of appropriate shock therapy in patients who receive implantable device therapy in a real-world setting: From the israeli ICD registry","volume":"12","author":"Sabbag","year":"2015","journal-title":"Heart Rhythm"},{"key":"B50","doi-asserted-by":"publisher","first-page":"104674","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":"Comput. Med. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1161\/CIRCULATIONAHA.106.653568","article-title":"Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction","volume":"115","author":"Schmidt","year":"2007","journal-title":"Circulation."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.jacc.2005.11.045","article-title":"Population-based analysis of sudden cardiac death with and without left ventricular systolic dysfunction","volume":"47","author":"Stecker","year":"2006","journal-title":"J. Am. Coll. Card."},{"key":"B53","doi-asserted-by":"publisher","first-page":"H1573","DOI":"10.1152\/ajpheart.00109.2006","article-title":"A model for human ventricular tissue","volume":"286","author":"ten Tusscher","year":"2004","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"B54","doi-asserted-by":"crossref","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":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1016\/j.jacc.2018.08.1038","article-title":"Fourth universal definition of myocardial infarction (2018)","volume":"72","author":"Thygesen","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ccl.2007.01.002","article-title":"Assessment of ventricular function with cardiovascular magnetic resonance","volume":"25","author":"Walsh","year":"2007","journal-title":"Cardiol. Clin."},{"key":"B57","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/0002-9149(82)90292-2","article-title":"Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses","volume":"49","author":"Wit","year":"1982","journal-title":"Am. J. Cardiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1161\/01.RES.0000059301.81035.06","article-title":"Remodeling of gap junctional channel function in epicardial border zone of healing canine infarcts","volume":"92","author":"Yao","year":"2003","journal-title":"Circ. Res."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.834747\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T10:22:21Z","timestamp":1648549341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.834747\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,24]]},"references-count":58,"alternative-id":["10.3389\/fphys.2022.834747"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.834747","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,24]]},"article-number":"834747"}}