Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Anthracycline-induced cardiomyopathy: risk prediction, prevention and treatment

Nature Reviews Cardiology volume 22, pages 551–563 (2025)Cite this article

Subjects

Abstract

Anthracyclines are the cornerstone of treatment for many malignancies. However, anthracycline cardiotoxicity is a considerable concern given that it can compromise the clinical effectiveness of the treatment and patient survival despite early discontinuation of therapy or dose reduction. Patients with cancer receiving anthracycline treatment can have a reduction in their quality of life and likelihood of survival due to cardiotoxicity, irrespective of their oncological prognosis. Increasing knowledge about anthracycline cardiotoxicity has enabled the identification of patients who are candidates for anthracycline regimens and those who might develop anthracycline-induced cardiomyopathy. Anthracycline cardiotoxicity is a unique and evolving phenomenon that begins with myocardial cell damage, progresses to reduced left ventricular ejection fraction, and culminates in symptomatic heart failure if it is not promptly detected and treated. Early risk stratification can be guided by imaging or biomarkers. In this Review, we present a comprehensive and clinically useful approach to cardiomyopathy related to anthracycline therapy, encompassing its epidemiology, definition, mechanisms, novel classifications, risk factors and patient risk stratification, diagnostic approaches (including imaging and biomarkers), treatment guidelines algorithms, and the role of new cardioprotective drugs that are used for the treatment of heart failure.

Key points

  • Anthracycline cardiotoxicity is a complex phenomenon that evolves over time, involving not only cardiomyocytes but also other components of myocardial tissue.

  • A complete and accurate risk stratification before the initiation of anthracycline therapy, including risk scores, echocardiographic evaluation and cardiac biomarkers, is essential to define the subsequent surveillance and treatment protocol.

  • A multidisciplinary approach actively involving the oncologist and cardiologist is essential to plan a patient’s therapeutic and preventive choices.

  • Although the treatment options for patients who develop heart failure after anthracycline therapy are well defined, the appropriate treatment approaches for primary and secondary prevention in patients who develop subclinical cardiotoxicity are uncertain.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Pathophysiology of anthracycline cardiotoxicity.
Fig. 2: Surveillance protocol during anthracycline therapy.

Similar content being viewed by others

References

  1. Octavia, Y. et al. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J. Mol. Cell Cardiol. 52, 1213–1225 (2012).

    Article  CAS  PubMed  Google Scholar 

  2. Henriksen, P. A. Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart 104, 971–977 (2018).

    Article  CAS  PubMed  Google Scholar 

  3. Zamorano, J. L. et al. 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). Eur. Heart J. 37, 2768–2801 (2016).

    Article  PubMed  Google Scholar 

  4. Armenian, S. H. et al. Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. 16, e123–e136 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lyon, A. R. et al. 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). Eur. Heart J. 43, 4229–4361 (2022).

    Article  PubMed  Google Scholar 

  6. Dimarco, A. et al. ‘Daunomycin’, a new antibiotic of the rhodomycin group. Nature 201, 706–707 (1964).

    Article  CAS  PubMed  Google Scholar 

  7. Dubost, M. et al. A new antibiotic with cytostatic properties: rubidomycin [French]. C. R. Hebd. Seances Acad. Sci. 257, 1813–1815 (1963).

    CAS  PubMed  Google Scholar 

  8. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G. & Gianni, L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 56, 185–229 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S. & Navik, U. Doxorubicin-induced cardiotoxicity: an update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed. Pharmacother. 139, 111708 (2021).

    Article  CAS  PubMed  Google Scholar 

  10. Tan, C., Tasaka, H., Yu, K.-P., Murphy, M. L. & Karnofsky, D. A. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer 20, 333–353 (1967).

    Article  CAS  PubMed  Google Scholar 

  11. Middleman, E., Luce, J. & Frei, E. Clinical trials with adriamycin. Cancer 28, 844–850 (1971).

    Article  CAS  PubMed  Google Scholar 

  12. Swain, S. M., Whaley, F. S. & Ewer, M. S. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97, 2869–2879 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. Arcamone, F. et al. Synthesis and antitumor activity of 4-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin, and their beta anomers. Cancer Treat. Rep. 60, 829–834 (1976).

    CAS  PubMed  Google Scholar 

  14. Danesi, R., Fogli, S., Gennari, A., Conte, P. & Del Tacca, M. Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs. Clin. Pharmacokinet. 41, 431–444 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Jain, K. K. et al. A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J. Clin. Oncol. 3, 818–826 (1985).

    Article  CAS  PubMed  Google Scholar 

  16. Ryberg, M. et al. Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J. Clin. Oncol. 16, 3502–3508 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Toffoli, G. et al. Dose-finding and pharmacologic study of chronic oral idarubicin therapy in metastatic breast cancer patients. Clin. Cancer Res. 6, 2279–2287 (2000).

    CAS  PubMed  Google Scholar 

  18. Anderlini, P. et al. Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia. J. Clin. Oncol. 13, 2827–2834 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. Ichikawa, Y. et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J. Clin. Invest. 124, 617–630 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Marinello, J., Delcuratolo, M. & Capranico, G. Anthracyclines as topoisomerase II poisons: from early studies to new perspectives. IJMS 19, 3480 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Qiu, Y., Jiang, P. & Huang, Y. Anthracycline-induced cardiotoxicity: mechanisms, monitoring, and prevention. Front. Cardiovasc. Med. 10, 1242596 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang, S. et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med. 18, 1639–1642 (2012).

    Article  PubMed  Google Scholar 

  23. Chatterjee, K., Zhang, J., Honbo, N. & Karliner, J. S. Doxorubicin cardiomyopathy. Cardiology 115, 155–162 (2010).

    Article  CAS  PubMed  Google Scholar 

  24. Fang, X. et al. Ferroptosis as a target for protection against cardiomyopathy. Proc. Natl Acad. Sci. USA 116, 2672–2680 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Amgalan, D. et al. A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy. Nat. Cancer 1, 315–328 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Li, M. et al. Phosphoinositide 3-kinase gamma inhibition protects from anthracycline cardiotoxicity and reduces tumor growth. Circulation 138, 696–711 (2018).

    Article  CAS  PubMed  Google Scholar 

  27. Cappetta, D. et al. Doxorubicin targets multiple players: a new view of an old problem. Pharmacol. Res. 127, 4–14 (2018).

    Article  CAS  PubMed  Google Scholar 

  28. Cardinale, D., Iacopo, F. & Cipolla, C. M. Cardiotoxicity of anthracyclines. Front. Cardiovasc. Med. 7, 26 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cardinale, D., Biasillo, G. & Cipolla, C. M. Curing cancer, saving the heart: a challenge that cardioncology should not miss. Curr. Cardiol. Rep. 18, 51 (2016).

    Article  PubMed  Google Scholar 

  30. Franco, V. I., Henkel, J. M., Miller, T. L. & Lipshultz, S. E. Cardiovascular effects in childhood cancer survivors treated with anthracyclines. Cardiol. Res. Pract. 2011, 134679 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pinder, M. C., Duan, Z., Goodwin, J. S., Hortobagyi, G. N. & Giordano, S. H. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J. Clin. Oncol. 25, 3808–3815 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Harbeck, N., Ewer, M. S., De Laurentiis, M., Suter, T. M. & Ewer, S. M. Cardiovascular complications of conventional and targeted adjuvant breast cancer therapy. Ann. Oncol. 22, 1250–1258 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Cardinale, D., Biasillo, G., Salvatici, M., Sandri, M. T. & Cipolla, C. M. Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy. Exp. Rev. Mol. Diagn. 17, 245–256 (2017).

    Article  CAS  Google Scholar 

  34. Pocock, S. J. et al. Predictors of mortality and morbidity in patients with chronic heart failure. Eur. Heart J. 27, 65–75 (2006).

    Article  PubMed  Google Scholar 

  35. Mertens, A. C. et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J. Clin. Oncol. 19, 3163–3172 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Mulrooney, D. A. et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339, b4606 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Reulen, R. C. Long-term cause-specific mortality among survivors of childhood cancer. JAMA 304, 172–179 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Semeraro, G. C., Lamantia, G., Cipolla, C. M. & Cardinale, D. How to identify anthracycline-induced cardiotoxicity early and reduce its clinical impact in everyday practice. Kardiol. Pol. 79, 114–122 (2021).

    Article  PubMed  Google Scholar 

  39. Cardinale, D. et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 131, 1981–1988 (2015).

    Article  CAS  PubMed  Google Scholar 

  40. Giantris, A., Abdurrahman, L., Hinkle, A., Asselin, B. & Lipshultz, S. E. Anthracycline-induced cardiotoxicity in children and young adults. Crit. Rev. Oncol. Hematol. 27, 53–68 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Grenier, M. A. & Lipshultz, S. E. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin. Oncol. 25, 72–85 (1998).

    CAS  PubMed  Google Scholar 

  42. Jain, D., Russell, R. R., Schwartz, R. G., Panjrath, G. S. & Aronow, W. Cardiac complications of cancer therapy: pathophysiology, identification, prevention, treatment, and future directions. Curr. Cardiol. Rep. 19, 36 (2017).

    Article  PubMed  Google Scholar 

  43. Ferrans, V. J. Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat. Rep. 62, 955–961 (1978).

    CAS  PubMed  Google Scholar 

  44. Cai, F. et al. Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: preventive strategies and treatment. Mol. Clin. Oncol. 11, 15–23 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Berry, G. J. & Jorden, M. Pathology of radiation and anthracycline cardiotoxicity. Pediatr. Blood Cancer 44, 630–637 (2005).

    Article  PubMed  Google Scholar 

  46. Cardinale, D. et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109, 2749–2754 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. McDonagh, T. A. et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 42, 3599–3726 (2021).

    Article  CAS  PubMed  Google Scholar 

  48. Rossello, X. et al. Risk prediction tools in cardiovascular disease prevention: a report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP). Eur. J. Prev. Cardiol. 26, 1534–1544 (2019).

    Article  PubMed  Google Scholar 

  49. Lyon, A. R. et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio‐Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio‐Oncology Society. Eur. J. Heart Fail. 22, 1945–1960 (2020).

    Article  PubMed  Google Scholar 

  50. Rivero-Santana, B. et al. Anthracycline-induced cardiovascular toxicity: validation of the Heart Failure Association and International Cardio-Oncology Society risk score. Eur. Heart J. 46, 273–284 (2024).

    Article  Google Scholar 

  51. Kaboré, E. G. et al. Risk prediction models for cardiotoxicity of chemotherapy among patients with breast cancer: a systematic review. JAMA Netw. Open. 6, e230569 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Salz, T. et al. Preexisting cardiovascular risk and subsequent heart failure among non-Hodgkin lymphoma survivors. J. Clin. Oncol. 35, 3837–3843 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang, L. et al. Major cardiac events and the value of echocardiographic evaluation in patients receiving anthracycline-based chemotherapy. Am. J. Cardiol. 116, 442–446 (2015).

    Article  CAS  PubMed  Google Scholar 

  54. Araujo-Gutierrez, R. et al. Baseline global longitudinal strain predictive of anthracycline-induced cardiotoxicity. Cardiooncology 7, 4 (2021).

    PubMed  PubMed Central  Google Scholar 

  55. Charbonnel, C. et al. Assessment of global longitudinal strain at low-dose anthracycline-based chemotherapy, for the prediction of subsequent cardiotoxicity. Eur. Heart J. Cardiovasc. Imaging 18, 392–401 (2017).

    PubMed  Google Scholar 

  56. Neilan, T. G. et al. Left ventricular mass in patients with a cardiomyopathy after treatment with anthracyclines. Am. J. Cardiol. 110, 1679–1686 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Garrone, O. et al. Prediction of anthracycline cardiotoxicity after chemotherapy by biomarkers kinetic analysis. Cardiovasc. Toxicol. 12, 135–142 (2012).

    Article  CAS  PubMed  Google Scholar 

  58. Cardinale, D. et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J. Am. Coll. Cardiol. 36, 517–522 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Cardinale, D. et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann. Oncol. 13, 710–715 (2002).

    Article  CAS  PubMed  Google Scholar 

  60. Ky, B. et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J. Am. Coll. Cardiol. 63, 809–816 (2014).

    Article  CAS  PubMed  Google Scholar 

  61. Sandri, M. T. et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clin. Chem. 51, 1405–1410 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Inoue, K. et al. Early detection and prediction of anthracycline-induced cardiotoxicity: a prospective cohort study. Circ. J. 88, 751–759 (2024).

    Article  CAS  PubMed  Google Scholar 

  63. McMurray, J. J. V. et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 33, 1787–1847 (2012).

    Article  PubMed  Google Scholar 

  64. Plana, J. C., Thavendiranathan, P., Bucciarelli-Ducci, C. & Lancellotti, P. Multi-modality imaging in the assessment of cardiovascular toxicity in the cancer patient. JACC Cardiovasc. Imaging 11, 1173–1186 (2018).

    Article  PubMed  Google Scholar 

  65. Dobson, R. et al. BSE and BCOS guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab. JACC CardioOncol. 3, 1–16 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Romond, E. H. et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2–positive breast cancer. J. Clin. Oncol. 30, 3792–3799 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zagar, T. M., Cardinale, D. M. & Marks, L. B. Breast cancer therapy-associated cardiovascular disease. Nat. Rev. Clin. Oncol. 13, 172–184 (2016).

    Article  CAS  PubMed  Google Scholar 

  68. Ewer, M. S. & Ewer, S. M. Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol. 12, 547–558 (2015).

    Article  CAS  PubMed  Google Scholar 

  69. Mousavi, N. et al. Echocardiographic parameters of left ventricular size and function as predictors of symptomatic heart failure in patients with a left ventricular ejection fraction of 50–59% treated with anthracyclines. Eur. Heart J. Cardiovasc. Imaging 16, 977–984 (2015).

    PubMed  Google Scholar 

  70. Oikonomou, E. K. et al. Assessment of prognostic value of left ventricular global longitudinal strain for early prediction of chemotherapy-induced cardiotoxicity: a systematic review and meta-analysis. JAMA Cardiol. 4, 1007–1018 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Negishi, T. et al. Cardioprotection using strain-guided management of potentially cardiotoxic cancer therapy. JACC Cardiovasc. Imaging 16, 269–278 (2023).

    Article  PubMed  Google Scholar 

  72. Laufer-Perl, M. et al. Left atrial strain changes in patients with breast cancer during anthracycline therapy. Int. J. Cardiol. 330, 238–244 (2021).

    Article  PubMed  Google Scholar 

  73. Emerson, P. et al. Left atrial strain in cardiac surveillance of bone marrow transplant patients with prior anthracycline exposure. Int. J. Cardiol. 354, 68–74 (2022).

    Article  PubMed  Google Scholar 

  74. Michel, L. et al. Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta‐analysis. Eur. J. Heart Fail. 22, 350–361 (2020).

    Article  CAS  PubMed  Google Scholar 

  75. Fabiani, I. et al. Use of new and emerging cancer drugs: what the cardiologist needs to know. Eur. Heart J. 45, 1971–1987 (2024).

    Article  CAS  PubMed  Google Scholar 

  76. O’Brien, P. J. Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology 245, 206–218 (2008).

    Article  PubMed  Google Scholar 

  77. Apple, F. S. & Collinson, P. O. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin. Chem. 58, 54–61 (2012).

    Article  CAS  PubMed  Google Scholar 

  78. Tan, L.-L. & Lyon, A. R. Role of biomarkers in prediction of cardiotoxicity during cancer treatment. Curr. Treat. Options Cardio Med. 20, 55 (2018).

    Article  Google Scholar 

  79. Pudil, R. et al. Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio‐Oncology Study Group of the Heart Failure Association and the Cardio‐Oncology Council of the European Society of Cardiology. Eur. J. Heart Fail. 22, 1966–1983 (2020).

    Article  CAS  PubMed  Google Scholar 

  80. Sawaya, H. et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ. Cardiovasc. Imaging 5, 596–603 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Skovgaard, D., Hasbak, P. & Kjaer, A. BNP predicts chemotherapy-related cardiotoxicity and death: comparison with gated equilibrium radionuclide ventriculography. PLoS ONE 9, e96736 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Fallah-Rad, N. et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J. Am. Coll. Cardiol. 57, 2263–2270 (2011).

    Article  CAS  PubMed  Google Scholar 

  83. Cardinale, D. et al. Anthracycline-induced cardiomyopathy. J. Am. Coll. Cardiol. 55, 213–220 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Gongora, C. A. et al. Are sodium-glucose cotransporter-2 inhibitors the cherry on top of cardio-oncology care? Cardiovasc. Drugs Ther. https://doi.org/10.1007/s10557-024-07604-x (2024).

  85. Khouri, M. G. & Greene, S. J. Sodium-glucose co-transporter-2 inhibitor therapy during anthracycline treatment. JACC Heart Fail. 10, 568–570 (2022).

    Article  CAS  PubMed  Google Scholar 

  86. Camilli, M. et al. Sodium–glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond. Basic. Res. Cardiol. https://doi.org/10.1007/s00395-024-01059-9 (2024).

  87. Giangiacomi, F. et al. Case report: sodium-glucose cotransporter 2 inhibitors induce left ventricular reverse remodeling in anthracycline-related cardiac dysfunction – a case series. Front. Cardiovasc. Med. 10, 1250185 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  88. López-Sendón, J. et al. Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry. Eur. Heart J. 41, 1720–1729 (2020).

    Article  PubMed  Google Scholar 

  89. Ferdinandy, P. et al. Definition of hidden drug cardiotoxicity: paradigm change in cardiac safety testing and its clinical implications. Eur. Heart J. 40, 1771–1777 (2019).

    Article  CAS  PubMed  Google Scholar 

  90. Hensley, M. L. et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J. Clin. Oncol. 27, 127–145 (2009).

    Article  CAS  PubMed  Google Scholar 

  91. Swain, S. M. et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J. Clin. Oncol. 15, 1318–1332 (1997).

    Article  CAS  PubMed  Google Scholar 

  92. Tebbi, C. K. et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin’s disease. J. Clin. Oncol. 25, 493–500 (2007).

    Article  CAS  PubMed  Google Scholar 

  93. Van Dalen, E. C., Caron, H. N., Dickinson, H. O. & Kremer, L. C. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst. Rev. 2011, CD003917 (2011).

    PubMed  PubMed Central  Google Scholar 

  94. Vejpongsa, P. & Yeh, E. T. H. Prevention of anthracycline-induced cardiotoxicity. J. Am. Coll. Cardiol. 64, 938–945 (2014).

    Article  CAS  PubMed  Google Scholar 

  95. Zheng, H. & Zhan, H. Preventing anthracycline-associated heart failure: what is the role of dexrazoxane?: JACC: CardioOncology Controversies in Cardio-Oncology. JACC CardioOncol. 6, 318–321 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  96. De Baat, E. C. et al. Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines. Cochrane Database Syst. Rev. 9, CD014638 (2022).

    PubMed  Google Scholar 

  97. Omland, T., Heck, S. L. & Gulati, G. The role of cardioprotection in cancer therapy cardiotoxicity. JACC CardioOncol. 4, 19–37 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Cardinale, D. et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114, 2474–2481 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Bosch, X. et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies. J. Am. Coll. Cardiol. 61, 2355–2362 (2013).

    Article  CAS  PubMed  Google Scholar 

  100. Georgakopoulos, P. et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin‐treated lymphoma patients: a prospective, parallel‐group, randomized, controlled study with 36‐month follow‐up. Am. J. Hematol. 85, 894–896 (2010).

    Article  CAS  PubMed  Google Scholar 

  101. Kalay, N. et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J. Am. Coll. Cardiol. 48, 2258–2262 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Gulati, G. et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur. Heart J. 37, 1671–1680 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Avila, M. S. et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J. Am. Coll. Cardiol. 71, 2281–2290 (2018).

    Article  CAS  PubMed  Google Scholar 

  104. Cardinale, D. et al. Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: the International CardioOncology Society-one trial. Eur. J. Cancer 94, 126–137 (2018).

    Article  CAS  PubMed  Google Scholar 

  105. Avila, M. S. et al. Renin-angiotensin system antagonists and beta-blockers in prevention of anthracycline cardiotoxicity: a systematic review and meta-analysis. Arq. Bras. Cardiol. 120, e20220298 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Caspani, F. et al. Prevention of anthracycline-induced cardiotoxicity: a systematic review and meta-analysis. Intern. Emerg. Med. 16, 477–486 (2021).

    Article  PubMed  Google Scholar 

  107. Neilan, T. G. et al. Atorvastatin for anthracycline-associated cardiac dysfunction: the STOP-CA randomized clinical trial. JAMA 330, 528 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Hundley, W. G. et al. Statins and left ventricular ejection fraction following doxorubicin treatment. NEJM Evid. https://doi.org/10.1056/evidoa2200097 (2022).

  109. Thavendiranathan, P. et al. Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines. Eur. Heart J. Cardiovasc. Pharmacother. 9, 515–525 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Anker, S. D. et al. Empagliflozin in heart failure with a preserved ejection fraction. N. Engl. J. Med. 385, 1451–1461 (2021).

    Article  CAS  PubMed  Google Scholar 

  111. Abdel-Qadir, H. et al. The association of sodium–glucose cotransporter 2 inhibitors with cardiovascular outcomes in anthracycline-treated patients with cancer. JACC CardioOncol. 5, 318–328 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Gongora, C. A. et al. Sodium–glucose co-transporter-2 inhibitors and cardiac outcomes among patients treated with anthracyclines. JACC Heart Fail. 10, 559–567 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Daniele, A. J., Gregorietti, V., Costa, D. & López – Fernández, T. Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD – PILOT trial. Cardiooncology 10, 58 (2024).

    PubMed  PubMed Central  Google Scholar 

  114. Rafiyath, S. M. et al. Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis. Exp. Hematol. Oncol. 1, 10 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Harris, L. et al. Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma. Cancer 94, 25–36 (2002).

    Article  CAS  PubMed  Google Scholar 

  116. Gabizon, A., Shmeeda, H. & Barenholz, Y. Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin. Pharmacokinet. 42, 419–436 (2003).

    Article  CAS  PubMed  Google Scholar 

  117. Berkman, A. M., Hildebrandt, M. A. T. & Landstrom, A. P. The genetic underpinnings of anthracycline‐induced cardiomyopathy predisposition. Clin. Genet. 100, 132–143 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Leong, S. L., Chaiyakunapruk, N. & Lee, S. W. H. Candidate gene association studies of anthracycline-induced cardiotoxicity: a systematic review and meta-analysis. Sci. Rep. 7, 39 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Schneider, B. P. et al. Genome-wide association study for anthracycline-induced congestive heart failure. Clin. Cancer Res. 23, 43–51 (2017).

    Article  CAS  PubMed  Google Scholar 

  120. Wang, X. et al. Genome-wide association study identifies ROBO2 as a novel susceptibility gene for anthracycline-related cardiomyopathy in childhood cancer survivors. J. Clin. Oncol. 41, 1758–1769 (2023).

    Article  CAS  PubMed  Google Scholar 

  121. Aminkeng, F. et al. Recommendations for genetic testing to reduce the incidence of anthracycline‐induced cardiotoxicity. Brit J. Clin. Pharmacol. 82, 683–695 (2016).

    Article  CAS  Google Scholar 

  122. Liu, J. et al. Circulating hemopexin modulates anthracycline cardiac toxicity in patients and in mice. Sci. Adv. 8, eadc9245 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Jacobs, J. E. J. et al. Artificial intelligence electrocardiogram as a novel screening tool to detect a newly abnormal left ventricular ejection fraction after anthracycline-based cancer therapy. Eur. J. Prev. Cardiol. 31, 560–566 (2024).

    Article  PubMed  Google Scholar 

  124. Kwan, J. M., Oikonomou, E. K., Henry, M. L. & Sinusas, A. J. Multimodality advanced cardiovascular and molecular imaging for early detection and monitoring of cancer therapy-associated cardiotoxicity and the role of artificial intelligence and big data. Front. Cardiovasc. Med. 9, 829553 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Chang, W.-T. et al. An artificial intelligence approach for predicting cardiotoxicity in breast cancer patients receiving anthracycline. Arch. Toxicol. 96, 2731–2737 (2022).

    Article  CAS  PubMed  Google Scholar 

  126. Porter, C. et al. Permissive cardiotoxicity; the clinical crucible of cardio-oncology. JACC CardioOncol. 4, 302–312 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Liutkauskiene, S. et al. Retrospective analysis of the impact of anthracycline dose reduction and chemotherapy delays on the outcomes of early breast cancer molecular subtypes. BMC Cancer 18, 453 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Iacopo Fabiani, Michela Chianca.

Authors and Affiliations

  1. Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy

    Iacopo Fabiani

  2. Division of Cardiology, Cardiothoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Michela Chianca

  3. Cardioncology Unit, Cardioncology and Second Opinion Division, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy

    Carlo Maria Cipolla & Daniela Maria Cardinale

Authors
  1. Iacopo Fabiani
    View author publications

    Search author on:PubMed Google Scholar

  2. Michela Chianca
    View author publications

    Search author on:PubMed Google Scholar

  3. Carlo Maria Cipolla
    View author publications

    Search author on:PubMed Google Scholar

  4. Daniela Maria Cardinale
    View author publications

    Search author on:PubMed Google Scholar

Contributions

I.F. and M.C. wrote the manuscript. All the authors reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Iacopo Fabiani.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Cardiology thanks Aarti Asnani, Susan Dent and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fabiani, I., Chianca, M., Cipolla, C.M. et al. Anthracycline-induced cardiomyopathy: risk prediction, prevention and treatment. Nat Rev Cardiol 22, 551–563 (2025). https://doi.org/10.1038/s41569-025-01126-1

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41569-025-01126-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing