{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:48:04Z","timestamp":1753890484587,"version":"3.41.2"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"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. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology and study design<\/jats:title><jats:p>Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were grouped according to the presence of AMI and compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 47 patients with truncated outcomes after the first OHT. The median age was 59 years, 36 patients (76%) were male, 25 patients (53%) had a prior history of cardiac operation, and 21 patients (45%) were supported with a durable assist device before OHT. Of those, AMI was identified in 22 (47%) patients (AMI group), and 25 patients had no AMI (non-AMI group). Groups were comparable in baseline and perioperative data. Histopathological observations in AMI group included a non-significant higher incidence of antibody-mediated rejection Grade 1 or higher (pAMR \u2265 1) (32% vs. 12%, <jats:italic>P<\/jats:italic> = 0.154), and non-significant lower incidence of severe acute cellular rejection (ACR \u2265 2R) (32% vs. 40%, <jats:italic>P<\/jats:italic> = 0.762). Clinical observations in the AMI group found a significantly higher occurrence of severe primary graft dysfunction (68% vs. 20%, <jats:italic>P<\/jats:italic> = 0.001) and a highly significant shorter duration from transplantation to death or re-transplantation (42 days [IQR 26, 120] vs. 1,133 days [711\u20131,664], <jats:italic>P<\/jats:italic> &amp;lt; 0.0001). Those patients had a significantly higher occurrence of cardiac-related deaths (64% vs. 24%, <jats:italic>P<\/jats:italic> = 0.020). No difference was observed in other outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In heart transplant recipients with a truncated postoperative course leading to either death or re-transplantation, AMI in endomyocardial biopsies was a common pathological phenomenon, which correlated with the clinical occurrence of severe primary graft dysfunction. Those patients had significantly shorter survival times and higher cardiac-related deaths. The presence of AMI suggests a truncated course after OHT.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.1014796","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T11:02:28Z","timestamp":1667473348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinicopathological correlations in heart transplantation recipients complicated by death or re-transplantation"],"prefix":"10.3389","volume":"9","author":[{"given":"Michelle M.","family":"McDonald","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maks","family":"Mihalj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bihong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sriram","family":"Nathan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislava","family":"Matejin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Ottaviani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateja K.","family":"Jezovnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajko","family":"Radovancevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biswajit","family":"Kar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor D.","family":"Gregoric","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. Maximilian","family":"Buja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.2174\/1573403X09666131117163825","article-title":"Advanced therapies for end-stage heart failure.","volume":"11","author":"Katz","year":"2015","journal-title":"Curr Cardiol Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s11936-010-0093-6","article-title":"Mechanical circulatory support for advanced heart failure.","volume":"12","author":"Patel","year":"2010","journal-title":"Curr Treat Options Cardiovasc Med."},{"key":"B3","first-page":"854","article-title":"Mechanical circulatory support in acute heart failure.","volume":"39","author":"Gregoric","year":"2012","journal-title":"Tex Heart Inst J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1111\/jocs.15341","article-title":"Left ventricular assist devices: a comprehensive review of major clinical trials, devices, and future directions.","volume":"36","author":"Jefferson","year":"2021","journal-title":"J Card Surg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1161\/CIRCULATIONAHA.117.029753","article-title":"Honoring 50 years of clinical heart transplantation in circulation: in-depth state-of-the-art review.","volume":"137","author":"Stehlik","year":"2018","journal-title":"Circulation."},{"key":"B6","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1007\/s11897-019-00432-3","article-title":"Updates on heart transplantation.","volume":"16","author":"Shah","year":"2019","journal-title":"Curr Heart Fail Rep."},{"journal-title":"The International Society for Heart and Lung Transplantation, International Thoracic Organ Transplant (TTX) Registry.","year":"2019","key":"B7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-018-1018-3","article-title":"Complications of cardiac transplantation.","volume":"20","author":"Potena","year":"2018","journal-title":"Curr Cardiol Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.healun.2014.02.027","article-title":"Report from a consensus conference on primary graft dysfunction after cardiac transplantation.","volume":"33","author":"Kobashigawa","year":"2014","journal-title":"J Heart Lung Transplant."},{"key":"B10","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.carpath.2016.01.007","article-title":"Pathobiology of ischemic heart disease: past, present and future.","volume":"25","author":"Buja","year":"2016","journal-title":"Cardiovasc Pathol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.carpath.2019.06.002","article-title":"Pathobiology of cardiovascular diseases: an update.","volume":"42","author":"Buja","year":"2019","journal-title":"Cardiovasc Pathol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.599511","article-title":"Damage-associated molecular patterns in myocardial infarction and heart transplantation: the road to translational success.","volume":"11","author":"Silvis","year":"2020","journal-title":"Front Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.healun.2021.06.002","article-title":"Recipient and surgical factors trigger severe primary graft dysfunction after heart transplant.","volume":"40","author":"Benck","year":"2021","journal-title":"J Heart Lung Transplant."},{"key":"B14","first-page":"994","article-title":"Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study.","volume":"16","author":"Baroldi","year":"1997","journal-title":"J Heart Lung Transplant."},{"key":"B15","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1540-8191.2008.00790.x","article-title":"Brain death and donor heart dysfunction: implications in cardiac transplantation.","volume":"25","author":"Apostolakis","year":"2010","journal-title":"J Card Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.healun.2013.10.013","article-title":"Molecular markers of programmed cell death in donor hearts before transplantation.","volume":"33","author":"Marasco","year":"2014","journal-title":"J Heart Lung Transplant."},{"key":"B17","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.transproceed.2020.10.001","article-title":"Apoptotic markers in donor hearts after brain death vs circulatory death.","volume":"53","author":"Marasco","year":"2021","journal-title":"Transplant Proc."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13472","article-title":"Prevalence, determinants, and correlates of coagulation necrosis and contraction band necrosis in donor hearts.","volume":"33","author":"Guglin","year":"2019","journal-title":"Clin Transplant."},{"key":"B19","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.carpath.2015.06.002","article-title":"Pathological assessment of end-stage heart failure in explanted hearts in correlation with hemodynamics in patients undergoing orthotopic heart transplantation.","volume":"24","author":"Ottaviani","year":"2015","journal-title":"Cardiovasc Pathol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/S1053-2498(02)00558-2","article-title":"Functional evidence of reversible ischemic injury immediately after the sympathetic storm associated with experimental brain death.","volume":"22","author":"Ryan","year":"2003","journal-title":"J Heart Lung Transplant."},{"key":"B21","first-page":"122","article-title":"Acute allograft failure in thoracic organ transplantation.","volume":"15","author":"Jahania","year":"2000","journal-title":"J Card Surg."},{"key":"B22","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1097\/00007890-198805000-00025","article-title":"Injury of myocardial conduction tissue and coronary artery smooth muscle following brain death in the baboon.","volume":"45","author":"Novitzky","year":"1988","journal-title":"Transplantation."},{"key":"B23","first-page":"183","article-title":"Exploring histopathological correlates of primary graft dysfunction.","author":"Manzoor","year":"","journal-title":"Paper Presented at US and Canadian Academy of Pathology Meeting 2021."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1016\/j.healun.2005.03.019","article-title":"Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.","volume":"24","author":"Stewart","year":"2005","journal-title":"J Heart Lung Transplant."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/j.healun.2013.08.011","article-title":"The 2013 international society for heart and lung transplantation working formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation.","volume":"32","author":"Berry","year":"2013","journal-title":"J Heart Lung Transplant."},{"key":"B26","first-page":"443","article-title":"Focal myocytolysis of the heart.","volume":"31","author":"Schlesinger","year":"1955","journal-title":"Am J Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/0002-8703(75)90189-1","article-title":"Different types of myocardial necrosis in coronary heart disease: a pathophysiologic review of their functional significance.","volume":"89","author":"Baroldi","year":"1975","journal-title":"Am Heart J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1096\/fj.04-2263com","article-title":"Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart.","volume":"18","author":"Sharma","year":"2004","journal-title":"Faseb J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"256","DOI":"10.5858\/134.2.256","article-title":"The utility of C4d, C9, and troponin T immunohistochemistry in acute myocardial infarction.","volume":"134","author":"Jenkins","year":"2010","journal-title":"Arch Pathol Lab Med."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0000000000000440","article-title":"Pathobiology of myocardial ischemia and reperfusion injury: models, modes, molecular mechanisms, modulation and clinical applications.","author":"Buja","year":"2022","journal-title":"Cardiol Rev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1097\/00007890-199909270-00024","article-title":"Complement deposition in early cardiac transplant biopsies is associated with ischemic injury and subsequent rejection episodes.","volume":"68","author":"Baldwin","year":"1999","journal-title":"Transplantation."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1016\/j.athoracsur.2010.05.066","article-title":"Extracorporeal membrane oxygenation in primary graft failure after heart transplantation.","volume":"90","author":"Marasco","year":"2010","journal-title":"Ann Thorac Surg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1016\/j.transproceed.2016.02.073","article-title":"Clinical factors implicated in primary graft dysfunction after heart transplantation: a single-center experience.","volume":"48","author":"Quintana-Quezada","year":"2016","journal-title":"Transplant Proc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1097\/TP.0b013e3181e6f1eb","article-title":"Factors associated with primary graft failure after heart transplantation.","volume":"90","author":"Russo","year":"2010","journal-title":"Transplantation."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/j.transproceed.2011.12.075","article-title":"Impact of warm ischemia time on survival after heart transplantation.","volume":"44","author":"Marasco","year":"2012","journal-title":"Transplant Proc."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01621","article-title":"Non-ischemic heart preservation via hypothermic cardioplegic perfusion induces immunodepletion of donor hearts resulting in diminished graft infiltration following transplantation.","volume":"11","author":"Critchley","year":"2020","journal-title":"Front Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"268","DOI":"10.12659\/AOT.907753","article-title":"Oxygen consumption of the aerobically-perfused cardioplegic donor heart at different temperatures.","volume":"23","author":"Qin","year":"2018","journal-title":"Ann Transplant."},{"key":"B38","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1093\/icvts\/ivu432","article-title":"Preservation of the donor heart: from basic science to clinical studies.","volume":"20","author":"Minasian","year":"2015","journal-title":"Interact Cardiovasc Thorac Surg."},{"journal-title":"International Thoracic Organ Transplant (TTX) Registry Data Slides.","year":"2021","key":"B39"},{"key":"B40","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3109\/14017431.2016.1154598","article-title":"Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours.","volume":"50","author":"Steen","year":"2016","journal-title":"Scand Cardiovasc J."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12636","article-title":"Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation.","volume":"28","author":"L\u00e4ngin","year":"2021","journal-title":"Xenotransplantation."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16782-9","article-title":"A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation.","volume":"11","author":"Nilsson","year":"2020","journal-title":"Nat Commun."},{"key":"B43","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/978-3-030-55244-2_7","article-title":"Cardiac replacement, assistance, repair or regeneration for heart failure.","author":"Tang","year":"2021","journal-title":"Transplantation Surgery."},{"key":"B44","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/MOT.0000000000000175","article-title":"Organ preservation review: history of organ preservation.","volume":"20","author":"Cameron","year":"2015","journal-title":"Curr Opin Organ Transplant."},{"key":"B45","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/aps.2017.182","article-title":"Organ preservation: from the past to the future.","volume":"39","author":"Jing","year":"2018","journal-title":"Acta Pharmacol Sin."},{"key":"B46","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/978-3-030-55244-2_6","article-title":"Organ Preservation.","author":"Kirnap","year":"2021","journal-title":"Transplantation Surgery."},{"key":"B47","first-page":"765","article-title":"Cellular and molecular mechanisms of endothelial ischemia\/reperfusion injury: perspectives and implications for postischemic myocardial protection.","volume":"8","author":"Yang","year":"2016","journal-title":"Am J Transl Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s10741-019-09794-1","article-title":"Primary graft dysfunction after heart transplantation: a thorn amongst the roses.","volume":"24","author":"Singh","year":"2019","journal-title":"Heart Fail Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1016\/j.healun.2015.08.003","article-title":"The registry of the international society for heart and lung transplantation: thirty-second official adult heart transplantation report\u20132015; focus theme: early graft failure.","volume":"34","author":"Lund","year":"2015","journal-title":"J Heart Lung Transplant."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1111\/jocs.14274","article-title":"Primary graft dysfunction after heart transplantation: outcomes and resource utilization.","volume":"34","author":"Quader","year":"2019","journal-title":"J Card Surg."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1111\/ajt.14588","article-title":"Primary graft dysfunction after heart transplantation: incidence, trends, and associated risk factors.","volume":"18","author":"Nicoara","year":"2018","journal-title":"Am J Transplant."},{"key":"B52","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1097\/MOT.0000000000000523","article-title":"Primary graft dysfunction in heart transplantation.","volume":"23","author":"DePasquale","year":"2018","journal-title":"Curr Opin Organ Transplant."},{"key":"B53","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.carpath.2014.05.001","article-title":"Predicting the development of cardiac allograft vasculopathy.","volume":"23","author":"Seki","year":"2014","journal-title":"Cardiovasc Pathol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.1097\/TP.0000000000002983","article-title":"Association of clinical rejection versus rejection on protocol biopsy with cardiac allograft vasculopathy in pediatric heart transplant recipients.","volume":"104","author":"Asimacopoulos","year":"2020","journal-title":"Transplantation."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1111\/ajt.15721","article-title":"Coronary computed tomography-angiography quantitative plaque analysis improves detection of early cardiac allograft vasculopathy: a pilot study.","volume":"20","author":"Miller","year":"2020","journal-title":"Am J Transplant."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1111\/tri.13973","article-title":"Clinical implementation of coronary computed tomography angiography for routine detection of cardiac allograft vasculopathy in heart transplant patients.","volume":"34","author":"Nous","year":"2021","journal-title":"Transpl Int."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14523","article-title":"Coronary imaging of cardiac allograft vasculopathy predicts current and future deterioration of left ventricular function in patients with orthotopic heart transplantation.","volume":"36","author":"Reddy","year":"2022","journal-title":"Clin Transplant."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1687.e9","DOI":"10.1016\/j.cjca.2018.08.022","article-title":"Coronary vasospasm following heart transplantation: rapid progression to aggressive cardiac allograft vasculopathy.","volume":"34","author":"Bertic","year":"2018","journal-title":"Can J Cardiol."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2020.100590","article-title":"Noninvasive biomarkers for prediction and diagnosis of heart transplantation rejection.","volume":"35","author":"Khachatoorian","year":"2021","journal-title":"Transplant Rev."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1014796\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T11:02:39Z","timestamp":1667473359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1014796\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":59,"alternative-id":["10.3389\/fcvm.2022.1014796"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.1014796","relation":{},"ISSN":["2297-055X"],"issn-type":[{"type":"electronic","value":"2297-055X"}],"subject":[],"published":{"date-parts":[[2022,11,3]]},"article-number":"1014796"}}