Review Article

Risk Assessment and Management of Anthracycline and HER2 Receptor Inhibitor-Induced Cardiomyopathy

Authors: Eiman Jahangir, MD, MPH, Sangeeta Shah, MD, Kelly Shum, MBBS, Caitlin Baxter, BS, Jill D. Fitzpatrick, PA-C, John Cole, MD, Yvonne Gilliland, MD, Nichole M. Polin, MD

Abstract

With the advent and increased use of chemotherapeutic agents and radiation therapy, cancer survival rates have increased. With increased survival, both acute and chronic cardiotoxic adverse effects have emerged. The growing need for managing the treatment of individuals with chemotherapy-induced cardiotoxicity has led to the formation of cardio-oncology programs throughout the United States. These programs concentrate on many aspects of cardiac disease in the oncology patient. Of these, the cardiotoxic effects (particularly cardiomyopathy) of anthracyclines and HER2 receptor inhibitors are a large focus of cardio-oncology practice. Despite the increasing avaiability of these programs, no consensus guidelines have been established to provide a framework for treating these patients. This review describes the initial evaluation, risk assessment, and management of individuals receiving anthracycline and HER2 receptor inhibitor therapy for cardiomyopathy. These recommendations are supported by the current literature in this field.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783-792.
 
2. Dranitsaris G, Tran TM. Economic analyses of toxicity secondary to anthracycline-based breast cancer chemotherapy. Eur J Cancer 1995; 31A(13Y14): 2174Y-180.
 
3. Bovelli D, Plataniotis G, Roila F, et al. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann Oncol 2010;21(Suppl 5): v277-v282.
 
4. Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging 2012;5:596-603.
 
5. Poterucha JT, Kutty S, Lindquist RK, et al. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr 2012;25:733-740.
 
6. Cardinale D, Sandri MT, Martinoni A, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 2000;36:517-522.
 
7. 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. J Am Coll Cardiol 2014;63:809-816.
 
8. Suzuki T, Hayashi D, Yamazaki T, et al. Elevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 1998;136:362-363.
 
9. Sandri MT, Salvatici M, Cardinale D, et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clin Chem 2005;51:1405-1410.
 
10. Pichon MF, Cvitkovic F, Hacene K, et al. Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography. In Vivo 2005;19:567-576.
 
11. Dodos F, Halbsguth T, Erdmann E, et al. Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults. Clin Res Cardiol 2008;97:318-326.
 
12. Sawaya H, Sebag IA, Plana JC, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol 2011;107:1375-1380.
 
13. Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002;20:1215-1221.
 
14. Chen J, Long JB, Hurria A, et al. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol 2012;60:2504-2512.
 
15. Bowles EJ, Wellman R, Feigelson HS, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst 2012;104:1293-1305.
 
16. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003;97:2869-2879.
 
17. Guglin M, Aljayeh M, Saiyad S, et al. Introducing a new entity: chemotherapy-induced arrhythmia. Europace 2009;11:1579-1586.
 
18. Middleman E, Luce J, Frei E 3rd. Clinical trials with adriamycin. Cancer 1971;28:844-850.
 
19. Dindogru A, Barcos M, Henderson ES, et al. Electrocardiographic changes following adriamycin treatment. Med Pediatr Oncol 1978;5:65-71.
 
20. Binah O, Cohen IS, Rosen MR. The effects of adriamycin on normal and ouabain-toxic canine Purkinje and ventricular muscle fibers. Circ Res 1983;53:655-662.
 
21. Cardinale D, Colombo A, Torrisi R, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol 2010;28:3910-3916.
 
22. Kang Y, Xu X, Cheng L, et al. Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy. Eur J Heart Fail 2014;16:300-308.
 
23. Herman EH, Zhang J, Lipshultz SE, et al. Correlation between serum levels of cardiac troponin-Tand the severity of the chronic cardiomyopathy induced by doxorubicin. J Clin Oncol 1999;17:2237-2243.
 
24. Adamcova M, Simnek T, Kaiserova H, et al. In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity. Toxicology 2007;237:218-228.
 
25. Simnek T, Klimtova I, Adamcova M, et al. Cardiac troponin T as an indicator of reduced left ventricular contractility in experimental anthracycline-induced cardiomyopathy. Cancer Chemother Pharmacol 2003;52:431-434.
 
26. Cardinale D, Sandri MT, Martinoni A, et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol 2002;13:710-715.
 
27. Sandri MT, Cardinale D, Zorzino L, et al. Minor increases in plasma troponin I predict decreased left ventricular ejection fraction after high-dose chemotherapy. Clin Chem 2003;49:248-252.
 
28. Cardinale D, Sandri MT, Colombo A, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 2004;109:2749-2754.
 
29. Cardinale D, Sandri MT. Role of biomarkers in chemotherapy-induced cardiotoxicity. Prog Cardiovasc Dis 2010;53:121-129.
 
30. Chuang ML, Hibberd MG, Salton CJ, et al. I Importance of imaging method over imaging modality in noninvasive determination of left ventricular volumes and ejection fraction: assessment by two- and three-Coll Cardiol 2000;35:477-484.
 
31. D’Hooge J, Heimdal A, Jamal F, et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr 2000;1:154170.
 
32. Kowalski M, Kukulski T, Jamal F, et al. Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects. Ultrasound Med Biol 2001;27:1087-1097.
 
33. Szulik M, Pappas CJ, Jurcut R, et al. Clinical validation of a novel speckle-tracking-based ejection fraction assessment method. J Am Soc Echocardiogr 2011;24:1092-1100.
 
34. Jaworski C, Mariani JA, Wheeler G, et al. Cardiac complications of thoracic irradiation. J Am Coll Cardiol 2013;61:2319-2328.
 
35. Mulrooney DA, Yeazel MW, Kawashima T, 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.
 
36. van Leeuwen-Segarceanu EM, Bos WJ, Dorresteijn LD, et al. Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. Cancer Treat Rev 2011;37:391-403.
 
37. Lee PJ, Mallik R. Cardiovascular effects of radiation therapy: practical approach to radiation therapy-induced heart disease. Cardiol Rev 2005;13:80-86.
 
38. Veinot JP, Edwards WD. Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases. Hum Pathol 1996;27:766-773.
 
39. Darby SC, Ewertz M, Hall P. Ischemic heart disease after breast cancer radiotherapy. N Engl J Med 2013;368:2527.
 
40. Lancellotti P, Nkomo VT, Badano LP, et al. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imag 2013;14:721-740.
 
41. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:1810-1852.
 
42. Bosch X, Rovira M, Sitges 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;61:2355-2362.
 
43. Okumura K, Jin D, Takai S, Miyazaki M. Beneficial effects of angiotensin-converting enzyme inhibition in adriamycin-induced cardiomyopathy in hamsters. Jpn J Pharmacol 2002;88:183-188.
 
44. Cardinale D, Colombo A, Sandri MT, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin- converting enzyme inhibition. Circulation 2006;114:2474-2481.
 
45. Nakamae H, Tsumura K, Terada Y, et al. Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer 2005;104:2492-2498.
 
46. Georgakopoulos P, Roussou P, Matsakas E, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol 2010;85:894-896.
 
47. Choe JY, Combs AB, Folkers K. Potentiation of the toxicity of Adriamycin by propranolol. Res Commun Chem Pathol Pharmacol 1978;21:577-580. .
 
48. Bernstein D, Fajardo G, Zhao M, et al. Differential cardioprotective/ cardiotoxic effects mediated by beta-adrenergic receptor subtypes. Am J Physiol Heart Circ Physiol 2005;289:H2441-H2449.
 
49. El-Shitany NA, Tolba OA, El-Shanshory MR, et al. Protective effect of carvedilol on adriamycin-induced left ventricular dysfunction in children with acute lymphoblastic leukemia. J Card Fail 2012;18:607-613.
 
50. Kalay N, Basar E, Ozdogru I, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 2006;48:2258-2262.
 
51. Kaya MG, Ozkan M, Gunebakmaz O, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol 2013;167:2306-2310.
 
52. Cardinale D, Colombo A, Lamantia G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010;55:213-220.
 
53. Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 2005;23:7820-7826.