Ejection Fraction Decline and Cardiotoxicity Following Anthracycline Chemotherapy: A Risk-Focused Study from an Indonesian Tertiary Care Center

Rizkyastari  Onny; Tutik  Harjianti; Pendrik  Tandean; Syakib  Bakri; Himawan  Sanusi; Andi Alfian  Zainuddin

doi:10.63181/ujcvs.2025.33(2).75-80

Rizkyastari Onny Hasanuddin University, Makassar, Indonesia https://orcid.org/0009-0006-9762-4726
Tutik Harjianti Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0002-9731-5193
Pendrik Tandean Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0002-6600-4763
Syakib Bakri Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0002-6615-5166
Himawan Sanusi Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0003-3828-2958
Andi Alfian Zainuddin Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0003-4590-6407

DOI: https://doi.org/10.63181/ujcvs.2025.33(2).75-80

Keywords: Anthracycline, Cardiotoxicity, Cancer Therapy–Related Cardiac Dysfunction, Echocardiographic Surveillance, Cumulative Dose, Ejection Fraction

Abstract

Background. Anthracycline chemotherapy is a cornerstone of cancer treatment but poses a risk of cardiotoxicity, often presenting as cancer therapy–related cardiac dysfunction (CTRCD). Monitoring left ventricular ejection fraction (LVEF) is essential to detect early cardiac impairment and support safer treatment strategies.

Aim. To assess LVEF changes after six cycles of anthracycline therapy and identify predictive factors associated with CTRCD.

Materials and methods. This observational pre–post study included 74 patients treated with anthracyclines at Dr. Wahidin Sudirohusodo Hospital, Makassar, from 2024 to 2025. LVEF was measured via echocardiographic surveillance before and after treatment. Cardiotoxicity was defined as a ≥10 % decrease in LVEF to ≤50 %. Statistical tools included Wilcoxon signed-rank test, Chi-square, ROC curve analysis, and logistic regression.

Results. The mean LVEF significantly declined from 63.08 % to 56.76 % (p = 0.001). CTRCD occurred in 20.3 % of patients. Risk factors independently associated with cardiotoxicity included age ≥51 years (OR 2.80; p = 0.016) and cumulative anthracycline dose ≥457.5 mg/m² (OR 3.25; p = 0.004). When both factors were present, the risk increased nearly sixfold (OR 5.75; p = 0.001).

Conclusions. CTRCD was observed in one-fifth of patients following anthracycline therapy, with age and dose being significant contributors. These findings support the integration of risk-based echocardiographic surveillance into oncology care to ensure early detection and mitigate long-term cardiac complications.

References

Global Cancer Observatory. GLOBOCAN 2024: Cancer Incidence and Mortality Worldwide. Lyon, France: International Agency for Research on Cancer; 2024.
Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity. Eur Heart J. 2016;37(36):2768–2801. https://doi.org/10.1093/eurheartj/ehw211
Curigliano G, Lenihan D, Fradley M, et al. Cardiotoxicity of anticancer treatments: ESMO Clinical Practice Guidelines. Ann Oncol. 2020;31(2):171–190. https://doi.org/10.1016/j.annonc.2019.10.023
Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy. J Am Soc Echocardiogr. 2014;27(9):911–939. https://doi.org/10.1016/j.echo.2014.07.012
Lipshultz SE, Lipsitz SR, Sallan SE, et al. Long-term cardiovascular toxicity in children and adolescents treated with doxorubicin. N Engl J Med. 1995;332(12):1738–1744. https://doi.org/10.1056/NEJM199506293322602
Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215–1221. https://doi.org/10.1200/JCO.2002.20.5.1215
Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. J Am Coll Cardiol. 2009;53(15):e1–e90. https://doi.org/10.1016/j.jacc.2008.11.013
De Angelis A, Urbanek K, Cappetta D, et al. Doxorubicin cardiotoxicity and target cells: a broader perspective. Cardio-Oncology. 2016;2:5. https://doi.org/10.1186/s40959-016-0012-1
Kamelia T, Harjianti T, Tandean P. Perubahan konsentrasi NT-proBNP dan fraksi ejeksi ventrikel kiri pada pasien kemoterapi doxorubicin. J Penyakit Dalam Indones. 2017;4(2):78.
Azzam M, Wasef M, Khalaf H, Al-Habbaa А. 3D-based strain analysis and cardiotoxicity detection in cancer patients receiving chemotherapy. BMC Cancer. 2023;23:1. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11261-y
Curigliano G, Lenihan D, Fradley M, & Dent S, Jordan K. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31(2):171–190. https://doi.org/10.1016/j.annonc.2019.10.023
Cardinale D, Colombo A, Lamantia G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981–1988. https://doi.org/10.1161/CIRCULATIONAHA.114.013777
Sawaya H, Sebag IA, Plana JC, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107(9):1375–1380. https://doi.org/10.1016/j.amjcard.2011.01.006
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin. Cancer. 2003;97(11):2869–2879. https://doi.org/10.1002/cncr.11407
Kang M, Koo H, Yang DH, et al. Cardioprotective effect of early dexrazoxane use in anthracycline-treated pediatric patients. J Chemother. 2012;24(5):292–296. https://doi.org/10.1179/1973947812Y.0000000038
Chen VZZ, Law HY, Chew FLM, et al. Cardiotoxicity after anthracycline chemotherapy for childhood cancer in a multiethnic Asian population. Front Pediatr. 2021;9:639603. https://doi.org/10.3389/fped.2021.639603
Wahdiyat M, Harjianti T, Tandean P. Gambaran perubahan ekokardiografi pada pasien kanker yang mendapat terapi doxorubicin [Specialist thesis]. Makassar: Universitas Hasanuddin; 2022.
Lyon AR, López-Fernández T, Couch LS, 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. 2022;43(41):4229-4361. DOI: 10.1093/eurheartj/ehac244
Herrmann J, Lenihan D, Armenian S, et al. Defining cardiovascular toxicities of cancer therapies: an IC-OS consensus statement. Eur Heart J. 2022;43(4):280–299. https://doi.org/10.1093/eurheartj/ehab674
Lancellotti P, Cosyns B, editors. The EACVI Echo Handbook. Oxford: European Society of Cardiology Publications; 2016. https://doi.org/10.1093/med/9780198713623.001.0001