New opportunities for preclinical diagnostics of antitumor therapy cardiotoxicity: results of an observational study

Aim. To study new possibilities of the potential of speckle tracking echocardiography for detecting early subclinical cardiotoxicity of chemo- and targeted therapy.
Material and methods. 150 patients with a verified oncological diagnosis, with a very high or high risk of cardiotoxicity, determined by the Mayo Clinic scale, were included in the prospective observational study at the Department of Hospital Therapy No. 1 of the Russian Medical University of the Ministry of Health of Russia in 2021-2023. All enrolled patients were recommended to take a fixed combination of the ACE inhibitor perindopril and the beta-blocker bisoprolol (5+5 mg) 5-7 days before the start of chemo-targeted therapy. Patients with a very high risk of cardiotoxicity who were diagnosed with ischemic chronic heart failure or stable coronary artery disease, or post-myocardial infarction, were additionally recommended to take long-acting trimetazidine OD at a dose of 80 mg once daily. At the second visit, the main group (n=84, receiving cardioprotective drugs) and the comparison group (n=66, not receiving cardioprotective drugs) were formed. All patients at the time of inclusion in the study, as well as 1, 3, 6, 9 and 12 months after the start of antitumor therapy, underwent the following assessment: collecting complaints, anamnesis data, physical examination, ECG registration in 12 standard leads, and a two-dimensional echocardiogram with the measurement of left ventricular (LV) global longitudinal strain (GLS).
Results. Primary drug prophylaxis in cancer patients with high and very high risk of cardiotoxicity was associated with a 2.7-fold decrease in significant cardiovascular complications. The development of chronic heart failure in the main group was noted 7 times less frequently than in the comparison group (n=1 (1.2%) vs n=7 (10.6%), p<0.05), a decrease in GLS LV 2.6 times (n=5 (5.9%) vs n=13 (19.7%), p<0.05). During the observation of oncological patients receiving chemo- and targeted therapy, it was found that a specific pattern, previously not described, was revealed in patients with developed systolic dysfunction upon visual assessment of the longitudinal strain of the LV. A decrease in contractility was noted in all LV basal segments, visually displayed by a pale or even blue color along the circumference of the diagram, with the presence of compensatory hyperkinesia of LV apical segments. LV strain reduction in the basal segments along the circumference of the outer part of the polar diagram >-18%, compensatory hyperkinesia of LV apical segments contractility <-18% in the inner part of the diagram compared to the initially determined values of the LV longitudinal strain before the start of antitumor therapy is an early, preclinical sign of cardiotoxicity.
Conclusion. The detection of typical changes in local longitudinal strain should be considered as an early sign of cardiotoxicity with a subsequent change in treatment tactics: temporary or permanent withdrawal of the drugs that caused cardiovascular complications, the appointment of cardioprotective therapy with ACE inhibitors, beta-adrenergic blockers and myocardial cytoprotectors.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwie for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63. DOI:10.3322/caac.21834.

2. Kaprin AD, Starinsky VV, Shakhzadova AO, editors. The state of oncological care for the population of Russia in 2023. Moscow: PA. Herzen Moscow Oncology Research Institute — branch of the National Medical Research Center of Radiology of the Ministry of Health of the Russian Federation, 2024. (In Russ.) ISBN: 978-5-85502-297-1.

3. Vasyuk YA, Shupenina EY, Vyzhigin DA, Novosel EO. Cardioncology: a new challenge of our time. Cardio-Oncology: A Guide for Physicians. Moscow: GEOTARMedia; 2025. (In Russ.) ISBN: 978-5-9704-9003-7.

4. Herrmann J, Lerman A, Sandhu NP, et al. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin Proc. 2014;89(9):1287- 306. DOI:10.1016/j.mayocp.2014.05.013.

5. Lyon AR, López-Fernández T, Couch LS, et al.; ESC Scientific Document Group. 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):4229-361. DOI:10.1093/eurheartj/ehac244. Erratum in: Eur Heart J. 2023;44(18):1621. DOI:10.1093/eurheartj/ehad196.

6. Kouwenberg TW, van Dalen EC, Feijen EAM, et al. Acute and early-onset cardiotoxicity in children and adolescents with cancer: a systematic review. BMC Cancer. 2023;23(1):866. DOI:10.1186/s12885-023-11353-9.

7. Li L, Jiang X, Xie Q. Prognostic value of left ventricular global longitudinal strain on speckle echocardiography for predicting chemotherapy-induced cardiotoxicity in breast cancer patients: A systematic review and meta-analysis. Echocardiography. 2023;40(4):306-17. DOI:10.1111/echo.15548.

8. Vasyuk YuA, Shupenina EY, Novosel EO, et al. Potential of primary drug prevention of cardiotoxicity in the context of anticancer therapy. Russian Journal of Cardiology. 2022;27(12):5258. (In Russ.) DOI:10.15829/1560-4071-2022-5258.

9. Tanaka H. Efficacy of echocardiography for differential diagnosis of left ventricular hypertrophy: special focus on speckle-tracking longitudinal strain. J Echocardiogr. 2021;19(2):71-9. DOI:10.1007/s12574-020-00508-3.

10. Eidenschink AB, Schröter G, Müller-Weihrich S, Stern H. Myocardial high-energy phosphate metabolism is altered after treatment with anthracycline in childhood. Cardiol Young. 2000;10(6):610-7. DOI:10.1017/s1047951100008891.

11. Tallarico D, Rizzo V, Di Maio F, et al. Myocardial cytoprotection by trimetazidine against anthracycline-induced cardiotoxicity in anticancer chemotherapy. Angiology. 2003;54(2):219-27. DOI:10.1177/000331970305400212.

12. Song FY, Shi J, Guo Y, et al. Assessment of biventricular systolic strain derived from the two-dimensional and three-dimensional speckle tracking echocardiography in lymphoma patients after anthracycline therapy. Int J Cardiovasc Imaging. 2017;33(6):857-68. DOI:10.1007/s10554-017-1082-6.

13. Negishi T, Thavendiranathan P, Penicka M, et al. Cardioprotection Using StrainGuided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial. JACC Cardiovasc Imaging. 2023;16(3):269-78. DOI:10.1016/j.jcmg.2022.10.010.

14. Marwick TH, Dewar E, Nolan M, et al. Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial. Eur Heart J. 2024;45(41):4414-24. DOI:10.1093/eurheartj/ehae574.

15. Васюк Ю.А., Школьник Е.Л., Несветов В.В. и др. Нарушения метаболизма миокарда на фоне химиотерапевтического лечения, а также возможности их коррекции. CardioСоматика. 2013;(4):20-4.

16. Tase AG, Man MG, Tase A, et al. Trimetazidine added-on therapy could lower the risk of incidental left ventricular dysfunction with or without heart failure in epirubicinum recipients for breast cancer [abstract]. JACC. 2017;69(11 Suppl):917. DOI:10.1016/S0735-1097(17)34306-1.

17. Donne MG, Iannielli A, Capozza P, et al. Cardioprotective effect of Trimetazidine in patients with early breast cancer receiving anthracycline-based chemotherapy [abstract]. Eur Heart J. 2020. 41(Suppl 2):880. DOI:10.1093/ehjci/ehaa946.0880.

18. Pascale C, Fornengo P, Epifani G et al. Cardioprotection of trimetazidine and anthracycline-induced acute cardiotoxic effects. Lancet. 2002;359(9312):1153-4. DOI:10.1016/S0140-6736(02)08135-7.

19. Larsen CM, Mulvagh SL. Cardio-oncology: what you need to know now for clinical practice and echocardiography. Echo Res Pract. 2017;4(1):R33-R41. DOI:10.1530/ERP-17-0013.