{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:16:47Z","timestamp":1790435807733,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the \u201ccollateral damage\u201d of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase II\u03b2 inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools\u2014specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping\u2014has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity.<\/jats:p>","DOI":"10.3390\/ijms27072973","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T10:07:13Z","timestamp":1774433233000},"page":"2973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiotoxicity of Antitumor Agents: Therapeutic Challenges in Heart Failure with Reduced and Preserved Ejection Fraction"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-9870","authenticated-orcid":false,"given":"Marco","family":"Tana","sequence":"first","affiliation":[{"name":"Internal Medicine and Cardiovascular Ultrasound Unit, Medical Department, Saint Annunziata Hospital, 66100 Chieti, Italy"},{"name":"School of Internal Medicine, Faculty of Medicine, G. D\u2019Annunzio University, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachele","family":"Piccinini","sequence":"additional","affiliation":[{"name":"School of Oncology Diseases, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-2104","authenticated-orcid":false,"given":"Giada","family":"Pinterpe","sequence":"additional","affiliation":[{"name":"School of Oncology Diseases, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettore","family":"Porreca","sequence":"additional","affiliation":[{"name":"Internal Medicine and Cardiovascular Ultrasound Unit, Medical Department, Saint Annunziata Hospital, 66100 Chieti, Italy"},{"name":"School of Internal Medicine, Faculty of Medicine, G. D\u2019Annunzio University, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9529-2960","authenticated-orcid":false,"given":"Rossana","family":"Berardi","sequence":"additional","affiliation":[{"name":"School of Oncology Diseases, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-7866","authenticated-orcid":false,"given":"Claudio","family":"Tana","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, ASL Taranto, 74121 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/1097-0142(197308)32:2<302::AID-CNCR2820320205>3.0.CO;2-2","article-title":"A clinicopathologic analysis of adriamycin cardiotoxicity","volume":"32","author":"Lefrak","year":"1973","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrcardio.2015.65","article-title":"Cardiotoxicity of anticancer treatments","volume":"12","author":"Ewer","year":"2015","journal-title":"Nat. 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