Plasma Galectin-3 as a Predictor of Cardiac Dysfunction in Patients Undergoing Doxorubicin Chemotherapy: A Prospective Cohort Study
Keywords:
Galectin-3, cardiotoxicity, Doxorubicin, Cardiac dysfunction, echocardiography, global longitudinal strain (GLS)Abstract
Background: Doxorubicin is widely used in chemotherapy in oncology. However, it is associated with dose-dependent cardiotoxicity. Thus, early detection of cardiac dysfunction is crucial to preventing heart failure. This study aimed to evaluate plasma Galectin-3 levels, a biomarker of fibrosis and inflammation, as a predictive biomarker of cardiac dysfunction in cancer patients receiving doxorubicin chemotherapy. Methods: This observational prospective cohort study was conducted from June 2024 to February 2025 at the Integrated Cardiac Service of Cipto Mangunkusumo National General Hospital (RSCM) and Dharmais Cancer Hospital in Jakarta. Fifty-five patients completed plasma Galectin-3 and echocardiographic assessments at three time points: pre-chemotherapy, post-chemotherapy cycle 2, and post-cycle 4. Cardiac dysfunction was defined by a decrease in LVEF ≥ 10% or a GLS reduction ≥ 15%. Results: No cardiac dysfunction was observed pre-chemotherapy, but 34.5% and 50.9% of patients developed dysfunction after cycles 2 and 4, respectively. Galectin-3 levels increased significantly post-cycle 4 (mean: 46.89 ± 18.34 ng/mL; p < 0.05). Receiver operating characteristic analysis showed that post-cycle 4 Galectin-3 levels predicted cardiac dysfunction with an area under the curve of 0.767 (95% CI: 0.638–0.897; p = 0.001), 92.9% sensitivity, and 59.3% specificity at a cut-off of ≥ 37.28 ng/mL. Significant correlations were observed between Galectin-3 and GLS (r = 0.54; p = 0.00) but not LVEF. Conclusion: Plasma Galectin-3 levels, particularly after chemotherapy cycle 4, are sensitive biomarkers for detecting cardiac dysfunction in patients receiving doxorubicin. Integrating Galectin-3 with GLS may provide better detection of subclinical cardiotoxicity. Additionally, monitoring Galectin-3 levels may help identify high-risk patients requiring cardioprotective strategiesReferences
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79.
Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Annals of Internal Medicine. 1979;91(5):710–7.
Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22), 1981–1988.
Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature Medicine. 2012;18(11): 1639–42.
Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology. 2017;35(8):893–911.
Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography. 2014;27(9):911–39.
Sharma UC, Pokharel S, van Brakel TJ, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110(19):3121–8.
de Boer RA, Yu L, van Veldhuisen DJ. Galectin-3 in cardiac remodeling and heart failure. Current Heart Failure Reports. 2010;7(1):1–8.
Liu YH, D'Ambrosio M, Liao TD, et al. Galectin-3 mediates aldosterone-induced cardiac fibrosis and dysfunction. Journal of the American College of Cardiology. 2013;62(5):e55.
Zaborska B, Sikora-Frac M, Smarz K, et al. The role of Galectin-3 in heart failure the diagnostic, prognostic and therapeutic potential where do we stand? International Journal of Molecular Sciences. 2023;24: 13111. https://doi.org/10.3390/ijms241713111
Lok DJ, Lok SI, Bruggink-André de la Porte PW, et al. Galectin-3 is an independent marker of cardiovascular mortality in heart failure patients. Clinical Research in Cardiology. 2010;99(5):311–7.
Christenson RH, Duh SH, Wu AH, et al. Multi-center determination of galectin-3 assay performance characteristics: anatomy of a novel assay for use in heart failure. Clinical Biochemistry. 2010;43(7–8):683–90.
Meijers WC, van der Velde AR, de Boer RA. Galectin-3: a link between heart failure, inflammation, and fibrosis. Heart Failure Clinics. 2018;14(2): 237–47.
Wu Y, Gao D, Xue J, Zuo Z. Galectin-3 and Myeloperoxidase may monitor cancer-therapy-related cardiotoxicity? A systematic review and meta-analysis. Biomolecules. 2022;12(12):1788. https://doi.org/10.3390/biom12121788
Thavendiranathan P, Poulin F, Lim KD, et al. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: A systematic review. Journal of the American College of Cardiology. 2014; 63(25 Pt A);2751–68.
Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. European Heart Journal. 2016;37(36):2768–801.
Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers for the early detection of cardiotoxicity in patients with breast cancer treated with anthracyclines and trastuzumab. Journal of the American Society of Echocardiography. 2012;25(12):1283–90.
Ky B, Putt M, Sawaya H, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. Journal of the American College of Cardiology. 2014;63(8):809–16.
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