Cardiotoxicity Induced by Anticancer Therapies: A Call for Integrated Cardio-Oncology Practice

Abstract

The introduction of novel oncologic therapies, including targeted agents, immunotherapies, and antibody-drug conjugates, has transformed the therapeutic landscape of cancer care. This evolution has resulted in a dual clinical scenario; while survival outcomes have markedly improved, leading to a growing population of long-term cancer survivors, an increasing incidence of previously unrecognized treatment-related toxicities has emerged. Among these, cardiovascular adverse events represent some of the most prevalent and clinically significant complications observed in both conventional chemotherapy and modern therapeutic regimens. Cardiotoxicity has become a major concern, with the potential to adversely affect not only cardiovascular health but also the continuity and efficacy of oncologic treatments, thereby impacting overall survival. This opinion paper synthesizes current evidence, identifies critical gaps in knowledge, and advocates for a multidisciplinary, evidence-based framework to guide the prevention, early detection, and optimal management of cardiotoxicity associated with anticancer therapies.

Keywords: anticancer drugs; cardio-oncology; cardiotoxicity; chemotherapy-induced cardiotoxicity; immunotherapy; targeted therapy.

Figure 1

Molecular mechanisms of anthracycline-induced cardiotoxicity. ABCB8, ATP-binding cassette, subfamily B, member 8; CaMKII, calmodulin-dependent protein kinase II; Cyt C, Cytochrome C; DOX, doxorubicin; IL-1, interleukin-1; IL-6, interleukin-6; NLRP3, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), RIPK3, receptor-interacting protein kinase 3; ROS, reactive oxygen species.

Figure 2

Cardiotoxicity associated with anti-VEGF therapy and taxane-based treatment in a 66-year-old woman with hypertension and a history of recurrent ER−/HER2− breast cancer. (A) Baseline strain analysis before starting paclitaxel plus bevacizumab, showing reduced GLS (−14%) with preserved LVEF (55%). (B) ECG during an episode of chest pain and dyspnea in February 2022, with elevated troponin and NT-proBNP, showing negative T waves in lateral leads and ST elevation in V1-V3. (C) Strain imaging at the time of symptoms showed further GLS impairment (−10%) and reduced LVEF (33%) (not explicit in the image). (D) One-year follow-up after heart failure therapy shows full recovery: LVEF 51%, GLS improved to −16%. ECG: electrocardiogram; ER: estrogen receptor; GLS: global longitudinal strain; HER2: human epidermal growth factor receptor 2; LVEF: left ventricular ejection fraction; NT-proBNP: N-terminal pro-B-type natriuretic peptide; VEGF: vascular endothelial growth factor.

Figure 3

Acute coronary syndrome related to fluoropyrimidine and anti-VEGF therapy in a 75-year-old male with colon cancer, previously treated with colectomy followed by FOLFIRI plus bevacizumab and subsequently capecitabine plus bevacizumab. (A) ECG on admission shows inferior STEMI with complete AV block and junctional escape rhythm with Left Bundle Branch Block pattern, which makes it difficult to value ST elevation in inferior leads. (B,C) Echocardiographic strain and myocardial work analysis reveal basal inferior and septal wall akinesia with preserved LVEF (55%). (D) Coronary angiography demonstrates proximal RCA occlusion (arrow), successfully treated with PCI and DES. AV: atrioventricular; DES: drug-eluting stent; ECG: electrocardiogram; FOLFIRI: folinic acid/5-fluorouracil/irinotecan; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention; RCA: right coronary artery; STEMI: ST-elevation myocardial infarction; VEGF: vascular endothelial growth factor.