Risk stratification and primary prevention of chemotherapy cardiotoxicity

Current recommendations for the primary prevention of chemotherapy cardiotoxicity are based on stratification of the risk of cardiovascular complications before anticancer treatment is initiated. The proposed cardiotoxicity risk scores take into account the presence of existing cardiovascular diseases, but do not take into account the therapy used for these diseases. Two clinical cases of patients with tumor diseases are presented. One patient had a high risk of cardiotoxicity, but even before the detection of a tumor process, he received a β-blocker, an angiotensin receptor blocker and a statin as a treatment strategy for coronary heart disease, which are recommended for the primary prevention of cardiovascular complications of chemotherapy. In this patient, development of cardiac dysfunction during ongoing antitumor treatment was not detected. In contrast, the second patient had a low risk of cardiotoxicity and was not given cardioprotective primary prophylaxis while on chemotherapy. However, this patient developed signs of severe cardiac dysfunction. It is possible that treatment of existing cardiovascular pathology with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers and statins significantly reduce the risk of cardiotoxicity, which must be taken into account stratifying the risk of cardiotoxicity. Accordingly, it seems necessary to further improve the scales for assessing the risk of cardiotoxicity.

1. Zamorano J.L., Gottfridsson C., Asteggiano R., Atar D., Badimon L., Bax J.J., Cardinale D. et al. The cancer patient and cardiology. Eur. J. Heart Fail. 2020;22(12):2290–2309. DOI: 10.1002/ejhf.1985.

2. Murkamilov I.T., Aitbaev K.A., Fomin V.V., Kudaibergenova I.O., Yusupov F.A., Murkamilova Zh.A. Cardiovascular complications in patients with cancer: focus on anthracycline-induced cardiotoxicity. Cardiovascular Therapy and Prevention. 2021;20(2):2583. (In Russ.). DOI: 10.15829/1728-8800-2021-2583.

3. Vasyuk Yu.A., Gendlin G.E., Emelina E.I., Shupenina E.Yu., Ballyuzek M.F., Barinova I.V. et al. Сonsensus statement of Russian experts on the prevention, diagnosis and treatment of cardiotoxicity of anticancer therapy. Russian Journal of Cardiology. 2021;26(9):4703. (In Russ.). DOI: 10.15829/1560-4071-2021-4703.

4. Lyon A.R., López-Fernández T., Couch L.S., Asteggiano R., Aznar M.C., Bergler-Klein J. 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): Developed by the Task Force on Cardio-Oncology of the European Society of Cardiology (ESC). Eur. Heart J. 2022;43(41):4229–4361. DOI: 10.1093/eurheartj/ehac244.

5. Mancilla T.R., Iskra B., Aune G.J. Doxorubicin-Induced Cardiomyopathy in Children. Compr. Physiol. 2019;9(3):905–931. DOI: 10.1002/cphy.c180017.

6. Felker G.M., Thompson R.E., Hare J.M., Hruban R.H., Clemetson D.E., Howard D.L. et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N. Engl. J. Med. 200013;342(15):1077–84. DOI: 10.1056/NEJM200004133421502.

7. Mulrooney D.A., Yeazel M.W., Kawashima T., Mertens A.C., Mitby P., Stovall M. 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. 2009;339:b4606. DOI: 10.1136/bmj.b4606.

8. López-Sendón J., Álvarez-Ortega C., Zamora Auñon P., Buño Soto A., Lyon A.R., Farmakis D. et al. Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry. Eur. Heart J. 2020;41(18):1720–1729. DOI: 10.1093/eurheartj/ehaa006.

9. Perez I.E., Taveras Alam S., Hernandez G.A., Sancassani R. Cancer Therapy-Related Cardiac Dysfunction: An Overview for the Clinician. Clin. Med. Insights. Cardiol. 2019;13:1179546819866445. DOI: 10.1177/1179546819866445.

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

11. Chazova I.E., Ageev F.T., Aksenova A.V., Vicenya M.V., Gilyarov M.Yu., Martynyuk T.V. et al. Eurasian clinical guidelines for cardiovascular complications of cancer treatments: diagnosis, prevention and treatment (2022). Eurasian heart journal. 2022;(1):6–79. (In Russ.). DOI: 10.38109/2225-1685-2022-1-6-79.

12. He D., Hu J., Li Y., Zeng X. Preventive use of beta-blockers for anthracycline-induced cardiotoxicity: A network meta-analysis. Front. Cardiovasc. Med. 2022;9:968534. DOI: 10.3389/fcvm.2022.968534.

13. Bosch X., Rovira M., Sitges M., Domènech A., Ortiz-Pérez J.T., de Caralt T.M. et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J. Am. Coll. Cardiol. 2013;61(23):2355–2362. DOI: 10.1016/j.jacc.2013.02.072.

14. Heck S.L., Mecinaj A., Ree A.H., Hoffmann P., Schulz-Menger J., Fagerland M.W. et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): extended follow-up of a 2×2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Circulation. 2021;143(25):2431–2440. DOI: 10.1161/CIRCULATIONAHA.121.054698.

15. Sobczuk P., Czerwińska M., Kleibert M., Cudnoch-Jędrzejewska A. Anthracycline-induced cardiotoxicity and renin-angiotensin-aldosterone system-from molecular mechanisms to therapeutic applications. Heart Fail. Rev. 2022;27(1):295–319. DOI: 10.1007/s10741-020-09977-1.