Cancer Therapy-Related Cardiac Dysfunction (CTRCD): A Cardiologist's Perspective on Mechanisms, Detection, and Cardioprotective Strategies

Yogi Puji Rachmawan; Witri  Pratiwi

doi:10.58344/ihj.v5i3.966

Authors

Yogi Puji Rachmawan Universitas Swadaya Gunung Jati
Witri Pratiwi Universitas Swadaya Gunung Jati

DOI:

https://doi.org/10.58344/ihj.v5i3.966

Keywords:

Cardio-Oncology, Cancer Therapy-Related Cardiac Dysfunction, Cardiotoxicity, Anthracyclines, Cardioprotection

Abstract

Advances in cancer treatment have improved survival but have also increased concerns regarding cancer therapy-related cardiac dysfunction (CTRCD), which may compromise cardiovascular health and continuity of oncologic treatment. This review aimed to synthesize the mechanisms, detection methods, and cardioprotective strategies associated with CTRCD from a cardiologist’s perspective and to discuss their relevance to cancer care in Indonesia. A narrative review was conducted using clinical practice guidelines, consensus statements, randomized controlled trials, observational studies, and foundational mechanistic research. Evidence was synthesized thematically without quantitative pooling. The synthesis highlighted distinct and overlapping mechanisms associated with anthracyclines, human epidermal growth factor receptor 2 (HER2)-targeted therapies, and other anticancer treatments, supporting individualized cardiovascular risk assessment. Baseline cardiovascular risk stratification, cardiac biomarkers, and echocardiography incorporating global longitudinal strain (GLS) provide complementary information for detecting myocardial injury and left ventricular dysfunction. Evidence regarding cardioprotective strategies remains heterogeneous; established interventions require risk-based selection, while statins and emerging therapies have demonstrated potential benefits in selected populations, often based on imaging endpoints rather than definitive clinical outcomes. Multidisciplinary cardio-oncology assessment is essential when considering modification or interruption of anticancer therapy. In Indonesia, a collaborative care framework could facilitate standardized referral, cardiovascular surveillance, and clinical documentation while accounting for differences in resource availability. In conclusion, CTRCD management requires integrated, treatment-specific strategies for prevention and early detection, supported by coordinated cardiology–oncology care. Proposed clinical pathways should undergo prospective evaluation to establish their feasibility, effectiveness, and ability.

References

Addison, D., Neilan, T. G., Barac, A., Scherrer-Crosbie, M., Okwuosa, T. M., Plana, J. C., et al. (2023). Cardiovascular imaging in contemporary cardio-oncology: A scientific statement from the American Heart Association. Circulation, 148(16), 1271–1286. https://doi.org/10.1161/CIR.0000000000001168

Aminkeng, F., Ross, C. J., Rassekh, S. R., Hwang, S., Rieder, M. J., Bhavsar, A. P., et al. (2016). Recommendations for genetic testing to reduce the incidence of anthracycline-induced cardiotoxicity. British Journal of Clinical Pharmacology, 82(3), 683–695.

Bhatti, A. W., Patel, R., Dani, S. S., Khadke, S., Makwana, B., Lessey, C., et al. (2024). SGLT2i and primary prevention of cancer therapy-related cardiac dysfunction in patients with diabetes. JACC: CardioOncology, 6(6), 863–875.

Bonatto, M. G., Avila, M. S., Ayub Ferreira, S. M., Torres, R. A., Costa, A. N., da Costa, N. R. A., et al. (2025). Sacubitril-valsartan for the prevention of anthracycline cardiotoxicity in patients with elevated cardiac troponin I concentration during chemotherapy: A double-blind randomized placebo-controlled clinical trial: The SARAH trial. Circulation, 152, 1742–1755.

Bosch, X., Rovira, M., Sitges, M., Domingo, E., Ninot, S., de Caralt, T. M., et al. (2013). Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: The OVERCOME trial. Journal of the American College of Cardiology, 61(23), 2355–2362. https://doi.org/10.1016/j.jacc.2013.02.072

Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263. https://doi.org/10.3322/caac.21834

Cardinale, D., Ciceri, F., Latini, R., Franzosi, M. G., Sandri, M. T., Civelli, M., et al. (2018). Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial. European Journal of Cancer, 94, 126–137. https://doi.org/10.1016/j.ejca.2018.02.005

Chen, W., Wu, Y., Li, W., Song, M., Xu, K., Wu, M., et al. (2025). Vericiguat improves cardiac remodelling and function in rats with doxorubicin-induced cardiomyopathy. ESC Heart Failure, 12(3), 1807–1817.

Contaldi, C., D'Aniello, C., Panico, D., Zito, A., Calabrò, P., Di Lorenzo, E., et al. (2025). Cancer-therapy-related cardiac dysfunction: Latest advances in prevention and treatment. Life, 15(3), Article 471.

Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., et al. (2024). Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer. https://gco.iarc.fr/today

Gulati, G., Heck, S. L., Ree, A. H., Hoffmann, P., Schulz-Menger, J., Fagerland, M. W., et al. (2016). 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. European Heart Journal, 37(21), 1671–1680. https://doi.org/10.1093/eurheartj/ehw022

Henriksen, P. A. (2018). Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention. Heart, 104(12), 971–977.

Herrmann, J., Lenihan, D., Armenian, S., Barac, A., Blaes, A., Cardinale, D., et al. (2022). Defining cardiovascular toxicities of cancer therapies: An International Cardio-Oncology Society (IC-OS) consensus statement. European Heart Journal, 43(4), 280–299. https://doi.org/10.1093/eurheartj/ehab674

Kang, D. W., Wilson, R. L., Christopher, C. N., Normann, A. J., Barnes, O., Lesansee, J. D., et al. (2022). Exercise cardio-oncology: Exercise as a potential therapeutic modality in the management of anthracycline-induced cardiotoxicity. Frontiers in Cardiovascular Medicine, 8, Article 805735.

Lyon, A. R., López-Fernández, T., Couch, L. S., Asteggiano, R., Aznar, M. C., Bergler-Klein, J., et al. (2022). 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). European Heart Journal, 43(41), 4229–4361. https://doi.org/10.1093/eurheartj/ehac244

Neilan, T. G., Quinaglia, T., Onoue, T., Mahmood, S. S., Drobni, Z. D., Gilman, H. K., et al. (2023). Atorvastatin for anthracycline-associated cardiac dysfunction: The STOP-CA randomized clinical trial. JAMA, 330(6), 528–536. https://doi.org/10.1001/jama.2023.11887

Oikonomou, E. K., Sangha, V., Dhingra, L. S., Aminorroaya, A., Coppi, A., Krumholz, H. M., et al. (2024). Artificial intelligence-enhanced risk stratification of cancer therapeutics-related cardiac dysfunction using electrocardiographic images. Circulation: Cardiovascular Quality and Outcomes, 18, Article e011504.

Palaskas, N. L., Ali, H. J., Koutroumpakis, E., Ganatra, S., & Deswal, A. (2024). Cardiovascular toxicity of immune therapies for cancer. BMJ, 385, Article e075859. https://doi.org/10.1136/bmj-2023-075859

Sánchez, B., González, P., Goveo, I., Contreras, P., Domínguez, L., Manrique, P., et al. (2025). Chemotherapy-induced cardiotoxicity: Mechanisms, detection and emerging therapies in cardio-oncology. Discoveries, 13(4), Article e217.

Tajstra, M., Dyrbu?, M., Rutkowski, T., Sk?adowski, K., Sosnowska-Pasiarska, B., Gó?d?, S., et al. (2023). Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): Design and rationale of the randomized trial. ESC Heart Failure, 10(5), 3174–3183.

Wakasa, M., Masaki, M., & Kajinami, K. (2025). Trastuzumab cardiotoxicity: Mechanism and management. Biological and Pharmaceutical Bulletin, 48(9), 1287–1294.

Zaha, V. G., Hayek, S. S., Alexander, K. M., Beckie, T. M., Hundley, W. G., Kondapalli, L., et al. (2021). Future perspectives of cardiovascular biomarker utilization in cancer survivors: A scientific statement from the American Heart Association. Circulation, 144(25), e551–e563.

Zhang, S., Liu, X., Bawa-Khalfe, T., Lu, L.-S., Lyu, Y. L., Liu, L. F., et al. (2012). Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature Medicine, 18(11), 1639–1642. https://doi.org/10.1038/nm.2919