{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:08Z","timestamp":1787026328784,"version":"build-2736575974"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"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:p>Considering the pandemic of both cardiovascular diseases and oncological diseases, there is an increasing need for the use of chemotherapy, which through various pathophysiological mechanisms leads to damage to heart function. Cardio toxicity of chemotherapy drugs can manifest itself in a variety of clinical manifestations, which is why establishing a valid diagnosis is a real mystery for clinicians. Acute systolic heart failure (AHF) due to the use of 5-fluorouracil (5-FU) is a rare occurrence if it is not associated with myocardial infarction, myocarditis or Takotsubo cardiomyopathy. Therefore, we decided to present a case of an 52-year-old male who was diagnosed with stage IV RAS wild-type adenocarcinoma of the rectum and in whom the direct toxic effect 5-FU is the main reason for the appearance of toxic cardiomyopathy.<\/jats:p>","DOI":"10.3389\/fcvm.2022.991886","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T01:24:45Z","timestamp":1666056285000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Case report: Acute toxic myocardial damage caused by 5-fluorouracil\u2014from enigma to success"],"prefix":"10.3389","volume":"9","author":[{"given":"Ratko","family":"Lasica","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Spasic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lazar","family":"Djukanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Trifunovic-Zamaklar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejan","family":"Orlic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Nedeljkovic-Arsenovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milika","family":"Asanin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"970","DOI":"10.3390\/ph14100970","article-title":"Anticancer drug-induced cardiotoxicity: insights and pharmacogenetics","volume":"14","author":"Adhikari","year":"2021","journal-title":"Pharmaceuticals (Basel)."},{"key":"B2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fcvm.2018.00009","article-title":"Cardiotoxicity of anticancer therapeutics","volume":"5","author":"Dong","year":"2018","journal-title":"Front Cardiovasc Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"847012","DOI":"10.3389\/fcvm.2022.847012","article-title":"Cardiotoxicity of anticancer drugs: molecular mechanisms and strategies for cardioprotection","volume":"9","author":"Morelli","year":"2022","journal-title":"Front Cardiovasc Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.5543\/tkda.2015.36005","article-title":"Capecitabine-induced coronary artery vasospasm in a patient who previously experienced a similar episode with fluorouracil therapy","volume":"44","author":"Karakulak","year":"2016","journal-title":"Turk Kardiyol Dern Ars."},{"key":"B5","doi-asserted-by":"publisher","first-page":"4426","DOI":"10.3390\/jcm10194426","article-title":"Cardiotoxicity of fluoropyrimidines: epidemiology, mechanisms, diagnosis, and management","volume":"10","author":"Jurczyk","year":"2021","journal-title":"J Clin Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s40959-019-0048-3","article-title":"5-FU induced cardiotoxicity: case series and review of the literature","volume":"5","author":"Yuan","year":"2019","journal-title":"Cardiooncology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"bcr2015213783","DOI":"10.1136\/bcr-2015-213783","article-title":"5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo: lessons from MRI","volume":"2016","author":"Fakhri","year":"2016","journal-title":"BMJ Case Rep"},{"key":"B8","unstructured":""},{"key":"B9","doi-asserted-by":"publisher","first-page":"900406","DOI":"10.3389\/fcvm.2022.900406","article-title":"Case report: oxaliplatin-induced third-degree atrioventricular block: first discovery of an important side-effect","volume":"9","author":"Chen","year":"2022","journal-title":"Front Cardiovasc Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1159\/000480661","article-title":"Oxaliplatin-induced acute ST-segment elevation mimicking myocardial infarction: a case report","volume":"41","author":"Weidner","year":"2018","journal-title":"Oncol Res Treat."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e776","DOI":"10.1200\/JCO.2011.36.4265","article-title":"Oxaliplatin-induced coronary vasospasm manifesting as Kounis syndrome: a case report","volume":"29","author":"Chang","year":"2011","journal-title":"J Clin Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.echo.2014.07.012","article-title":"Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"27","author":"Plana","year":"2014","journal-title":"J Am Soc Echocardiogr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1093\/eurheartj\/ehw211","article-title":"ESC Scientific Document Group. (2016) ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)","volume":"37","author":"Zamorano","year":"2016","journal-title":"Eur Heart J"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1093\/annonc\/mdw235","article-title":"ESMO consensus guidelines for the management of patients with metastatic colorectal cancer","volume":"27","author":"Van Cutsem","year":"2016","journal-title":"Ann Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e013361","DOI":"10.1161\/JAHA.119.013361","article-title":"Myocardial infarction with nonobstructive coronary arteries: a call for individualized treatment","volume":"8","author":"Mukherjee","year":"2019","journal-title":"J Am Heart Assoc."},{"key":"B16","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/eurheartj\/ehx393","article-title":"ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)","volume":"39","author":"Ibanez","year":"2018","journal-title":"Eur Heart J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1093\/eurheartj\/ehab088","article-title":"ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation","volume":"42","author":"Collet","year":"2021","journal-title":"Eur Heart J"},{"key":"B18","doi-asserted-by":"crossref","first-page":"e78","DOI":"10.1016\/j.jacc.2012.11.019","article-title":"2013 ACCF\/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"61","author":"O'Gara","year":"2013","journal-title":"J Am Coll Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1097\/HPC.0000000000000256","article-title":"Misdiagnosis of acute myocardial infarction: a systematic review of the literature","volume":"20","author":"Kwok","year":"2021","journal-title":"Crit Pathw Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1016\/j.jacc.2017.06.047","article-title":"risk of arterial thromboembolism in patients with cancer","volume":"70","author":"Navi","year":"2017","journal-title":"J Am Coll Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"590016","DOI":"10.3389\/fcvm.2021.590016","article-title":"challenges and management of acute coronary syndrome in cancer patients","volume":"8","author":"Costa","year":"2021","journal-title":"Front Cardiovasc Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s11897-019-0420-5","article-title":"The role of troponin for acute heart failure","volume":"16","author":"Harrison","year":"2019","journal-title":"Curr Heart Fail Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa0706824","article-title":"ADHERE investigators. Cardiac troponin and outcome in acute heart failure","volume":"358","author":"Peacock","year":"2008","journal-title":"N Engl J Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1067\/mhj.2001.111767","article-title":"Evidence of cardiac myolysis in severe nonischemic heart failure and the potential role of increased wall strain","volume":"141","author":"Logeart","year":"2001","journal-title":"Am Heart J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.ahj.2007.01.027","article-title":"Relation between cardiac troponin I and mortality in acute decompensated heart failure","volume":"153","author":"You","year":"2007","journal-title":"Am Heart J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1093\/annonc\/mdf170","article-title":"Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy","volume":"13","author":"Cardinale","year":"2002","journal-title":"Ann Oncol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e009635","DOI":"10.1161\/JAHA.118.009635","article-title":"Myocardial infarction with nonobstructive coronary arteries (MINOCA): it's time to face reality!","volume":"7","author":"Tamis-Holland","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1161\/CIRCULATIONAHA.111.026542","article-title":"Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease","volume":"124","author":"Reynolds","year":"2011","journal-title":"Circulation."},{"key":"B29","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1161\/01.cir.0000025609.13806.31","article-title":"Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study","volume":"106","author":"Rioufol","year":"2002","journal-title":"Circulation"},{"key":"B30","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.ancard.2011.07.011","article-title":"Plaque rupture and morphological characteristics of the culprit lesion in acute coronary syndromes without significant angiographic lesion: analysis by intravascular ultrasound","volume":"61","author":"Ouldzein","year":"2012","journal-title":"Ann Cardiol Angeiol (Paris)."},{"key":"B31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1093\/jnci\/djp440","article-title":"Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio- oncological prevention","volume":"102","author":"Albini","year":"2010","journal-title":"J Natl Cancer Inst."},{"key":"B32","first-page":"59","article-title":"Chemotherapy-induced Cardiotoxicity","volume":"8","author":"Florescu","year":"2013","journal-title":"Maedica."},{"key":"B33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s11886-021-01441-2","article-title":"5-FU Cardiotoxicity: vasospasm, myocarditis, and sudden death","volume":"23","author":"More","year":"2021","journal-title":"Curr Cardiol Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ehjcr\/ytz146","article-title":"Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features","volume":"3","author":"Joy","year":"2019","journal-title":"Eur Heart J Case Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"8507096","DOI":"10.1155\/2017\/8507096","article-title":"Induced takotsubo cardiomyopathy treated with impella assist device","volume":"2017","author":"Kabach","year":"2017","journal-title":"Case Rep Cardiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"178","DOI":"10.14503\/THIJ-15-5100","article-title":"Rapid extracorporeal membrane oxygenation overcomes fulminant myocarditis induced by 5-fluorouracil","volume":"43","author":"Amraotkar","year":"2016","journal-title":"Tex Heart Inst J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"243","DOI":"10.14797\/mdcj-15-4-243","article-title":"Heart failure in relation to anthracyclines and other chemotherapies","volume":"15","author":"Agunbiade","year":"2019","journal-title":"Methodist Debakey Cardiovasc J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1023\/A:1006416410198","article-title":"5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development","volume":"18","author":"Grem","year":"2000","journal-title":"Invest New Drugs."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1758835918780140","DOI":"10.1177\/1758835918780140","article-title":"5- fluorouracil and cardiotoxicity: a review","volume":"10","author":"Sara","year":"2018","journal-title":"Ther Adv Med Oncol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s11864-020-0719-1","article-title":"Cardiotoxicities of 5-Fluorouracil and Other Fluoropyrimidines","volume":"21","author":"Shiga","year":"2020","journal-title":"Curr Treat Options Oncol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e230499","DOI":"10.1136\/bcr-2019-230499","article-title":"Acute reversible left ventricular systolic dysfunction associated with 5-fluorouracil therapy: a rare and increasingly recognised cardiotoxicity of a commonly used drug","volume":"12","author":"Mishra","year":"2019","journal-title":"BMJ Case Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.ejca.2005.03.027","article-title":"The frequency and pattern of cardiotoxicity observed with capecitabine used in conjunction with oxaliplatin in patients treated for advanced colorectal cancer (CRC)","volume":"41","author":"Ng","year":"2005","journal-title":"Eur J Cancer."},{"key":"B43","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/clc.22007","article-title":"Treatment and outcomes of acute coronary syndrome in the cancer population","volume":"35","author":"Yusuf","year":"2012","journal-title":"Clin Cardiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s00280-005-0178-1","article-title":"Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine","volume":"58","author":"Jensen","year":"2006","journal-title":"Cancer Chemother Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/1748-717X-7-212","article-title":"5-FU-induced cardiac toxicity\u2013an underestimated problem in radiooncology?","volume":"7","author":"Steger","year":"2012","journal-title":"Radiat Oncol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"757196","DOI":"10.3389\/fonc.2021.757196","article-title":"Safety profile of oxaliplatin in 3,687 patients with cancer in china: a post-marketing surveillance study","volume":"11","author":"Yu","year":"2021","journal-title":"Front Oncol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.jcma.2013.05.001","article-title":"Oxaliplatin-induced acquired long QT syndrome with torsades de pointes and myocardial injury in a patient with dilated cardiomyopathy and rectal cancer","volume":"76","author":"Chang","year":"2013","journal-title":"J Chin Med Assoc."},{"key":"B48","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1159\/000331645","article-title":"Clinical and electrocardiography changes in patients treated with capecitabine","volume":"57","author":"Koca","year":"2011","journal-title":"Chemotherapy."},{"key":"B49","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1159\/000072334","article-title":"High incidence of angina pectoris in patients treated with 5-fluorouracil. A planned surveillance study with 102 patients","volume":"65","author":"Wacker","year":"2003","journal-title":"Oncology."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/annonc\/mdu055","article-title":"Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk","volume":"25","author":"Lestuzzi","year":"2014","journal-title":"Ann Oncol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e403","DOI":"10.1002\/onco.13536","article-title":"Myocardial ischemia induced by 5-fluorouracil: a prospective electrocardiographic and cardiac biomarker study","volume":"26","author":"Dyhl-Polk","year":"2021","journal-title":"Oncologist"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.ajem.2017.02.046","article-title":"Prinzmetal angina (Coronary vasospasm) associated with 5-fluorouracil chemotherapy","volume":"35","author":"Ben-Yakov","year":"2017","journal-title":"Am J Emerg Med"},{"key":"B53","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1253\/jcj.59.303","article-title":"case of 5-fluorouracil cardiotoxicity simulating acute myocardial infarction","volume":"5","author":"Mizuno","year":"1995","journal-title":"Jpn Circ J."},{"key":"B54","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00392-005-0159-8","article-title":"Coronary artery spasm induced by 5- fluorouracil","volume":"94","author":"Alter","year":"2005","journal-title":"Z Kardiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jccase.2019.08.005","article-title":"Atrial fibrillation observed in a patient with esophageal cancer treated with fluorouracil","volume":"20","author":"Moriyama","year":"2019","journal-title":"J Cardiol Cases."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1016\/j.jccase.2012.03.011","article-title":"5-Fluorouracil-induced coronary thrombosis: A case report and review of the literature","volume":"6","author":"Sorrentino","year":"2012","journal-title":"J Cardiol Cases."},{"key":"B57","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.ijcard.2014.06.094","article-title":"Diagnostic criteria for takotsubo syndrome: a call for consensus","volume":"176","author":"Redfors","year":"2014","journal-title":"Int J Cardiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.ahj.2007.11.008","article-title":"Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction","volume":"155","author":"Prasad","year":"2008","journal-title":"Am Heart J."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1093\/eurheartj\/ehr165","article-title":"The management of myocarditis","volume":"32","author":"Schultheiss","year":"2011","journal-title":"Eur Heart J."},{"key":"B60","doi-asserted-by":"publisher","first-page":"7","DOI":"10.4137\/CMC.S19703","article-title":"Reversible Cardiomyopathies","volume":"9","author":"Patel","year":"2015","journal-title":"Clin Med Insights Cardiol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.991886\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T01:24:51Z","timestamp":1666056291000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.991886\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":60,"alternative-id":["10.3389\/fcvm.2022.991886"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.991886","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]},"article-number":"991886"}}