{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:25:26Z","timestamp":1789662326741,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Patients with acute myeloid leukemia (AML) have a higher propensity for adverse cardiovascular outcomes, primarily due to the toxic effects of chemotherapeutic agents. The purpose of this systematic review is to explore the association of acute myeloid leukemia treatment with adverse cardiovascular events. Methods: We systematically screened the literature for studies providing comparative data on cardiovascular toxicities in patients treated for acute myeloid leukemia. After the initial search, 3649 papers were screened and a final total number of 46 were included for the review process. Results: Common chemotherapeutic agents used in AML may cause cardiovascular (CV) toxicities. A plethora of pathophysiological mechanisms are incriminated for these effects. Drug combinations may increase the risk in a synergistic way. In addition, common mutations of AML, personal history of previous cardiovascular disease and impaired heart function carry an increased complication risk. Biomarkers, as well as multimodality imaging, may be used for the early detection of cardiovascular toxicities. Conclusions: Increased risks of CV toxicity and comorbidities are observed among AML patients. With all the available diagnostic modalities, early detection and CV prevention strategies can improve the patient\u2019s prognosis and quality of life.<\/jats:p>","DOI":"10.3390\/cancers17030541","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:53:41Z","timestamp":1738832021000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Acute and Chronic Cardiovascular Adverse Events in Patients with Acute Myeloid Leukemia: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9120-0184","authenticated-orcid":false,"given":"Konstantinos C.","family":"Siaravas","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-4095","authenticated-orcid":false,"given":"Amalia I.","family":"Moula","sequence":"additional","affiliation":[{"name":"Achilopouleio General Hospital of Volos, 38222 Volos, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis S.","family":"Tzourtzos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5946-936X","authenticated-orcid":false,"given":"Christos E.","family":"Ballas","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7638-9217","authenticated-orcid":false,"given":"Christos S.","family":"Katsouras","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","article-title":"Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges","volume":"36","author":"Shallis","year":"2019","journal-title":"Blood Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1007\/s00277-024-05963-x","article-title":"Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia","volume":"103","author":"Prajapati","year":"2024","journal-title":"Ann. Hematol."},{"key":"ref_3","first-page":"38","article-title":"Cardiovascular Disease Among Patients with AML and CHIP-Related Mutations","volume":"4","author":"Schoffel","year":"2022","journal-title":"Cardio Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/CIRCULATIONAHA.115.020406","article-title":"Shared Risk Factors in Cardiovascular Disease and Cancer","volume":"133","author":"Koene","year":"2016","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.hfc.2016.12.006","article-title":"Cardio-oncology Related to Heart Failure: Common Risk Factors Between Cancer and Cardiovascular Disease","volume":"13","author":"Blaes","year":"2017","journal-title":"Heart Fail. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"oead073","DOI":"10.1093\/ehjopen\/oead073","article-title":"Association between heart failure and the incidence of cancer: A systematic review and meta-analysis","volume":"3","author":"Jaiswal","year":"2023","journal-title":"Eur. Heart J. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Konstantinidis, I., Tsokkou, S., Grigoriadis, S., Chrysavgi, L., and Gavriilaki, E. (2024). Cardiotoxicity in Acute Myeloid Leukemia in Adults: A Scoping Study. Cancers, 16.","DOI":"10.3390\/cancers16132474"},{"key":"ref_9","first-page":"75","article-title":"Cardiotoxicity of venetoclax in patients with acute myeloid leukemia: Comparison with anthracyclines","volume":"10","author":"Onoue","year":"2024","journal-title":"Cardiooncology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1111\/bjh.19336","article-title":"The heart of VIALE-A: Cardiac complications of hypomethylating agents and venetoclax in acute myeloid leukaemia","volume":"204","author":"Patel","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1080\/10428194.2017.1323268","article-title":"Cardiovascular effects of the addition of nilotinib to standard therapy for acute myeloid leukemia","volume":"59","author":"Larsen","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.3816\/CLM.2002.s.006","article-title":"Acute and long-term toxicities associated with gemtuzumabozogamicin (Mylotarg) therapy of acute myeloid leukemia","volume":"2","author":"Leopold","year":"2002","journal-title":"Clin. Lymphoma"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.amjcard.2024.06.033","article-title":"Symptomatic Heart Failure and Clonal Hematopoiesis-Related Mutations in Patients with Acute Myeloid Leukemia","volume":"226","author":"Kang","year":"2024","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/s41375-020-01043-x","article-title":"IDH1\/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction-a retrospective propensity score analysis","volume":"35","author":"Kattih","year":"2021","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109042","DOI":"10.1016\/j.thromres.2024.109042","article-title":"Acute cardiovascular complications of disseminated intravascular coagulation in acute myeloid leukemia","volume":"239","author":"Araji","year":"2024","journal-title":"Thromb. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1093\/eurheartj\/ehae188","article-title":"Rescue of cardiac dysfunction during chemotherapy in acute myeloid leukaemia by blocking IL-1alpha","volume":"45","author":"Zhou","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/MBC.0000000000001226","article-title":"Venous thromboembolism and acute myeloid leukemia: Risk factors and mortality in elderly white, black and Asian patients","volume":"34","author":"Faiz","year":"2023","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1182\/bloodadvances.2019000955","article-title":"Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: A Young SIOG review paper","volume":"4","author":"Neuendorff","year":"2020","journal-title":"Blood Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e35770","DOI":"10.1097\/MD.0000000000035770","article-title":"Anthracyclines and the risk of arrhythmias: A systematic review and meta-analysis","volume":"102","author":"Dean","year":"2023","journal-title":"Medicine"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhou, X., Weng, Y., Jiang, T., Ou, W., Zhang, N., Dong, Q., and Tang, X. (2023). Influencing factors of anthracycline-induced subclinical cardiotoxicity in acute leukemia patients. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11060-5"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6616265","DOI":"10.1155\/2021\/6616265","article-title":"Assessment and Management of Cardiotoxicity in Hematologic Malignancies","volume":"2021","author":"Bojan","year":"2021","journal-title":"Dis. Markers"},{"key":"ref_22","first-page":"CD014638","article-title":"Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines","volume":"9","author":"Mulder","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1177\/1078155219873014","article-title":"Evaluation of cardiomyopathy in acute myeloid leukemia patients treated with anthracyclines","volume":"26","author":"Mort","year":"2020","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1404092","DOI":"10.3389\/fphar.2024.1404092","article-title":"All-trans retinoic acid in hematologic disorders: Not just acute promyelocytic leukemia","volume":"15","author":"Chen","year":"2024","journal-title":"Front.Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hasbullah, J.S., Scott, E.N., Bhavsar, A.P., Gunaretnam, E.P., Miao, F., Soliman, H., Carleton, B.C., and Ross, C.J.D. (2022). All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0276541"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kordella, C., Lamprianidou, E., and Kotsianidis, I. (2021). Mechanisms of Action of Hypomethylating Agents: Endogenous Retroelements at the Epicenter. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.650473"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ijcard.2020.05.035","article-title":"Prevalence and incidence of various Cancer subtypes in patients with heart failure vs matched controls","volume":"316","author":"Schwartz","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13476","DOI":"10.1111\/ijcp.13476","article-title":"Management strategies and clinical outcomes of acute myocardial infarction in leukaemia patients: Nationwide insights from United States hospitalisations","volume":"74","author":"Mohamed","year":"2020","journal-title":"Int. J. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s13256-022-03280-3","article-title":"Acute myeloid leukemia causing acute thrombosis of the coronary arteries: A case report","volume":"16","author":"Ferrel","year":"2022","journal-title":"J. Med. Case Rep."},{"key":"ref_30","first-page":"e9551","article-title":"Acute Myocardial Infarction as Initial Manifestation of Acute Myeloid Leukemia: A Rare Manifestation of Leukostasis","volume":"12","author":"Manogna","year":"2020","journal-title":"Cureus"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/ccd.28432","article-title":"Percutaneous coronary intervention and in-hospital outcomes in patients with leukemia: A nationwide analysis","volume":"96","author":"Potts","year":"2020","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101465","DOI":"10.1016\/j.beha.2023.101465","article-title":"Cardio-oncology and transplantation for acute myeloid leukemia","volume":"36","author":"Singh","year":"2023","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106951","DOI":"10.1016\/j.leukres.2022.106951","article-title":"Effect of cumulative daunorubicin dose on cardiotoxicity after allogeneic stem cell transplantation","volume":"121","author":"Fujiwara","year":"2022","journal-title":"Leuk. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"bcr2016217210","DOI":"10.1136\/bcr-2016-217210","article-title":"Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: Literature review of management and prognostic factors","volume":"2016","author":"Shahzad","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1093\/eurheartj\/ehac244","article-title":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","volume":"43","author":"Lyon","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1111\/echo.14518","article-title":"Two-dimensional speckle-tracking strain detects subclinical cardiotoxicity in older patients treated for acute myeloid leukemia","volume":"36","author":"Cascino","year":"2019","journal-title":"Echocardiography"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.echo.2017.07.010","article-title":"Deformation Analysis of Myocardial Layers Detects Early Cardiac Dysfunction after Chemotherapy in Bone Marrow Transplantation Patients: A Continuous and Additive Cardiotoxicity Process","volume":"30","author":"Paraskevaidis","year":"2017","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.21873\/invivo.11420","article-title":"The Assessment of Left Ventricle Function and Subclinical Atherosclerosis in Patients with Acute Myeloid Leukemia","volume":"32","author":"Militaru","year":"2018","journal-title":"In Vivo"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1016\/j.jacc.2013.02.072","article-title":"Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: The OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)","volume":"61","author":"Bosch","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e016309","DOI":"10.1161\/JAHA.119.016309","article-title":"Cancer Mortality in Trials of Heart Failure with Reduced Ejection Fraction: A Systematic Review and Meta-Analysis","volume":"9","author":"Tini","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_41","first-page":"415","article-title":"Cardiac Interventions in Patients with Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review","volume":"5","author":"Leong","year":"2023","journal-title":"Cardio Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/ejh.12757","article-title":"The fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline-based therapy for the treatment of acute myeloid leukemia for patients with pre-existing cardiac disease","volume":"97","author":"Saini","year":"2016","journal-title":"Eur. J. Haematol."},{"key":"ref_43","first-page":"708","article-title":"Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients treated with anthracyclines for acute leukemia","volume":"114","author":"Horacek","year":"2013","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"AlAsmari, A.F., Alghamdi, A., Ali, N., Almeaikl, M.A., Hakami, H.M., Alyousef, M.K., AlSwayyed, M., Alharbi, M., Alqahtani, F., and Alasmari, F. (2022). Venetoclax Induces Cardiotoxicity through Modulation of Oxidative-Stress-Mediated Cardiac Inflammation and Apoptosis via NF-\u03baB and BCL-2 Pathway. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116260"},{"key":"ref_45","first-page":"90","article-title":"Differential cardiac impacts of hematological malignancies and solid tumors: A histopathological and biomarker study","volume":"10","author":"Udin","year":"2024","journal-title":"Cardiooncology"},{"key":"ref_46","first-page":"208","article-title":"Symptomatic Heart Failure in Acute Leukemia Patients Treated with Anthracyclines","volume":"1","author":"Kang","year":"2019","journal-title":"Cardio Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/pbc.22908","article-title":"Prevalence and predictors of anthracycline cardiotoxicity in children treated for acute myeloid leukaemia: Retrospective cohort study in a single centre in the United Kingdom","volume":"56","author":"Temming","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/bjh.14374","article-title":"Is it possible to cure childhood acute myeloid leukaemia without significant cardiotoxicity?","volume":"175","author":"Jarfelt","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"djv357","DOI":"10.1093\/jnci\/djv357","article-title":"Cardioprotection and Second Malignant Neoplasms Associated with Dexrazoxane in Children Receiving Anthracycline Chemotherapy: A Systematic Review and Meta-Analysis","volume":"108","author":"Shaikh","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_50","first-page":"58","article-title":"Use of EMPAgliflozin in the prevention of CARDiotoxicity: The EMPACARD\u2014PILOT trial","volume":"10","author":"Daniele","year":"2024","journal-title":"Cardiooncology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Vaziri, Z., Saleki, K., Aram, C., Alijanizadeh, P., Pourahmad, R., Azadmehr, A., and Ziaei, N. (2023). Empagliflozin treatment of cardiotoxicity: A comprehensive review of clinical, immunobiological, neuroimmune, and therapeutic implications. Biomed. Pharmacother., 168.","DOI":"10.1016\/j.biopha.2023.115686"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"138","DOI":"10.20517\/cdr.2022.133","article-title":"Resistance to energy metabolism\u2014Targeted therapy of AML cells residual in the bone marrow microenvironment","volume":"6","author":"Tabe","year":"2023","journal-title":"Cancer Drug Resist."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Jiang, Y., Li, M., and Yu, Q. (2023). Will nanomedicine become a good solution for the cardiotoxicity of chemotherapy drugs?. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1143361"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:27:36Z","timestamp":1760027256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cancers17030541"],"URL":"https:\/\/doi.org\/10.3390\/cancers17030541","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]}}}