Possibilities of modern echocardiographic technologies in the early diagnosis of the cardiotoxic effect of chemotherapy drugs anthracycline series in cancer patients

Chronic heart failure following chemotherapy for cancer is a relevant issue of an adverse cardiovascular prognosis and premature death in cancer patients. This category of patients requires thorough and chronic monitoring of the cardiovascular system, prevention and treatment of cardiovascular complications of chemotherapy, such as IHD, systolic or diastolic myocardial dysfunction, arterial or pulmonary hypertension, pulmonary thromboembolism, pericarditis, stroke, and peripheral vascular disease. However, many aspects of this important interdisciplinary issue presently remain understudied. For instance, it is still impossible to predict long-term consequences of chemotherapy for cancer and development of the associated cardiovascular complications listed above. Baseline evaluation of the risk for cardiovascular complications is a major component in management of such patients. High-risk patients need an individual, detailed schedule of cardiovascular treatment throughout and after the course of chemotherapy. Furthermore, early detection of subclinical myocardial dysfunction is critical for prevention of the most threatening cardiovascular complications of chemotherapy, CHF. Detecting impaired LV EF following chemotherapy is, unfortunately, only a late predictor of irreversible changes, such as toxic cardiomyopathy and clinically pronounced, rapidly progressing CHF. Markers of myocardial injury, high-sensitivity troponins and natriuretic peptides, in combination with up-to-date EchoCG technologies have been recently used. Their use, for instance, for evaluation of LV myocardial global longitudinal strain to detect early, reversible changes in structure and mechanics of the myocardium is promising for ultimate improvement of prediction for such patients.

химиотерапия, антрациклиновая кардиотоксичность, спекл-трекинг, продольная глобальная деформация ЛЖ, триметазидин, chemotherapy, anthracycline cardiotoxicity, speckle tracking, longitudinal global deformation of LV, trimetazidine

1. Unitt C, Montazeri K, Tolaney S, Moslehi J. Cardiology patient page. Breast cancer chemotherapy and your heart. Circulation. 2014;129 (25):e680-682. DOI:10.1161/cIRCULATIONAHA. 113.007181.

2. Hooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99 (5):365-75. DOI: 10.1093 /jnci/djk064.

3. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M 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. J Am Soc Echocardiogr. 2014;27 (9):911-39. DOI:10.1016/j. echo. 2014.07.012.

4. Steingart RM, Bakris GL, Chen HX, Chen M-H, Force T, Ivy SP et al. Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Am Heart J. 2012;163 (2):156-63. DOI:10.1016/j. ahj. 2011.10.018.

5. Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23 (34):8597-605. D0I:10.1200/JC0. 2005.02.5841.

6. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344 (11):783-92. D0I:10.1056/NEJ M200103153441101.

7. Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342 (15):1077-84. D0I:10.1056/NEJM200004133421502.

8. Negishi K, Negishi T, Haluska BA, Hare JL, Plana JC, Marwick TH. Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection. Eur Heart J Cardiovasc Imaging. 2014;15 (3):324-31. D0I:10.1093/ehjci/jet159.

9. Wang TJ, Evans JC, Benjamin EJ, Levy D, LeRoy EC, Vasan RS. Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation. 2003;108 (8):977-82. D0I:10.1161/01.CIR. 0000085166.44904.79.

10. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH et al. 2013 ACCF/AHA Guideline for the management of heart failure: executive summary. Journal of the American College of Cardiology. 2013;62 (16):1495-539. D0I:10.1016/j. jacc. 2013.05.020.

11. Bovelli D, Plataniotis G, Roila F, ESM0 Guidelines Working Group. Cardiotoxicity of chemotherapeutic agents and radiotherapy-rela ted heart disease: ESM0 Clinical Practice Guidelines. Ann Oncol. 2010;21 Suppl 5: v277-282. D0I:10.1093/annonc/mdq200.

12. Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102 (1):14-25. D0I:10.1093/jnci/djp440.

13. Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESM0 Clinical Practice Guidelines. Ann Oncol. 2012;23 Suppl 7: vii155-166. DOI: 10.1093/annonc/mds293.

14. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M 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. Eur Heart J Cardiovasc Imaging. 2014; 15 (10):1063-93. D0I:10.1093/ehjci/jeu192.

15. Yu C-M, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler imaging a new prognosticator for cardiovascular diseases. J Am Coll Cardiol. 2007;49 (19):1903-14. D0I:10.1016/j. jacc. 2007.01.078.

16. Thavendiranathan P, Grant AD, Negishi T, Plana JC, Popovic ZB, Marwick TH. Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: application to patients undergoing cancer chemotherapy. J Am Coll Cardiol. 2013;61 (1):77-84. D0I:10.1016/j. jacc. 2012.09.035.

17. Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55 (3):213-20. D0I:10.1016/j. jacc. 2009.03.095.

18. Wadhwa D, Fallah-Rad N, Grenier D, Krahn M, Fang T, Ahmadie R et al. Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study. Breast Cancer Res Treat. 2009;117 (2):357-64. D0I:10.1007/s10549-008-0260-6.

19. Kocabay G, Muraru D, Peluso D, Cucchini U, Mihaila S, Padayattil-Jose S et al. Normal left ventricular mechanics by two-dimensional speckle-tracking echocardiography. Reference values in healthy adults. Rev Esp Cardiol (Engl Ed). 2014;67 (8):651-8. D0I:10.1016/j. rec. 2013.12.009.

20. Agha H, Shalaby L, Attia W, Abdelmohsen G, Aziz OA, Rahman MYA. Early ventricular dysfunction after anthracycline chemotherapy in children. Pediatr Cardiol. 2016;37 (3):537-44. D0I:10.1007/s00246-015-1311-5.

21. Berk BC, Fujiwara K, Lehoux S. ECM remodeling in hypertensive heart disease. J Clin Invest. 2007;117 (3):568-75. D0I:10.1172/JCI31044.

22. Mondillo S, Galderisi M, Mele D, Cameli M, Lomoriello VS, Zacà V et al. Speckle-tracking echocardiography: a new technique for assessing myocardial function. J Ultrasound Med. 2011;30 (1):71-83.

23. Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N et al. Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle ( JUSTICE) study. Circ J. 2012;76 (11):2623-32.

24. Несветов В. В., Школьник Е. Л., Васюк Ю. А. Значение глобальной продольной систолической деформации по двухмерному изображению для ранней диагностики кардиотоксического действия химиопрепаратов (предварительные результаты). Журнал Сердечная Недостаточность. 2013; 14 (3):127-30 [Nesvetov V. V., Shkol'nik E. L., Vasyuk Yu. A. Znachenie global'noj prodol'noj sistolicheskoj deformaczii po dvuxmernomu izobrazheniyu dlya rannej diagnostiki kardiotoksicheskogo dejstviya ximiopreparatov (predvaritel'ny'e rezul'taty'). Zhurnal Serdechnaya Nedostatochnost'. 2013;14 (3):127-30].

25. Biswas M, Sudhakar S, Nanda NC, Buckberg G, Pradhan M, Roomi AU et al. Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography. 2013;30 (1):88-105. DOI:10.1111 /echo. 12079.

26. Tan TC, Scherrer-Crosbie M. Cardiac complications of chemotherapy: role ofimaging. Curr Treat Options Cardiovasc Med. 2014;16 (4):296.DOI:10.1007/s11936-014-0296-3.

27. Tarr A, Stoebe S, Tuennemann J, Baka Z, Pfeiffer D, Varga A et al. Early detection of cardiotoxicity by 2D and 3D deformation imaging in patients receiving chemotherapy. Echo Res Pract. 2015;2 (3):81-8. DOI:10.1530/ERP-14-0084.

28. Thavendiranathan P, Poulin F, Lim K-D, Plana JC, Woo A, Marwick TH. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol. 2014;63 (25 Pt A): 2751-68. DOI:10.1016/j. jacc. 2014.01.073.

29. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61 (4):212-36. DOI: 10.3322/caac. 20121.

30. Stoodley PW, Richards DAB, Meikle SR, Clarke J, Hui R, Thomas L. The potential role of echocardiographic strain imaging for evaluating cardiotoxicity due to cancer therapy. Heart Lung Circ. 2011;20 (1):3-9. DOI:10.1016/j. hlc. 2010.09.007.

31. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC 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 (5):596-603. DOI:10.1161 /CIRCIMAGING. 112.973321.

32. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Cohen V et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107 (9):1375-80. DOI: 10.1016/j. amjcard. 2011.01.006.

33. Negishi K, Negishi T, Hare JL, Haluska BA, Plana JC, Marwick TH. Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr. 2013;26 (5):493-8. DOI:10.1016/j. echo. 2013.02.008.

34. Toufan M, Pourafkari L, Ghahremani Nasab L, Esfahani A, Sanaat Z, Nikanfar A et al. Two-dimensional strain echocardiography for detection of cardiotoxicity in breast cancer patients under going chemotherapy. J Cardiovasc Thorac Res. 2017;9 (1):29-34. DOI:10.15171 /jcvtr. 2017.04.

35. Boyd A, Stoodley P, Richards D, Hui R, Harnett P, Vo K et al. Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study. PLoS ONE. 2017;12 (4):e0175544. DOI:10.1371/journal. pone. 0175544.

36. Tang Q, Jiang Y, Xu Y, Xia H. Speckle tracking echocardiography predicts early subclinical anthracycline cardiotoxicity in patients with breast cancer. J Clin Ultrasound. 2017;45 (4):222-30. DOI:10.1002/jcu. 22434.

37. Васюк Ю. А., Несветов В. В., Школьник Е. Л., Школьник Л. Д., Гендлин Г. Е. Возможности селективного ингибитора ионных f-каналов синусового узла ивабрадина в профилактике антрациклиновой кардиотоксичности у больных раком молочной железы. Рациональная фармакотерапия в кардиологии. 2017; 13 (2):184-90. DOI:10.20996/1819-6446-2017-13-2-184-190 [Vasyuk Yu. A., Nesvetov V. V., Shkol'nik E. L., Shkol'nik L. D., Gendlin G. E. Vozmozhnosti selektivnogo ingibitora ionny'x f-kanalov sinusovogo uzla ivabradina v profilaktike antracziklinovoj kardiotoksichnosti u bol'ny'x rakom molochnoj zhelezy'. Raczional'naya farmakoterapiya v kardiologii. 2017;13 (2):184-90. DOI: 10.20996/1819-6446-2017-13-2-184-190].

38. Fine NM, Shah AA, Han I-Y, Yu Y, Hsiao J-F, Koshino Y et al. Left and right ventricular strain and strain rate measurement in normal adults using velocity vector imaging: an assessment of reference values and intersystem agreement. Int J Cardiovasc Imaging. 2013;29 (3):571-80.DOI:10.1007/s10554-012-0120-7.

39. Marwick TH, Leano RL, Brown J, Sun J-P, Hoffmann R, Lysyansky P et al. Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging. 2009;2 (1):80-4. DOI:10.1016/j. jcmg. 2007.12.007.

40. Duncan AE, Alfirevic A, Sessler DI, Popovic ZB, Thomas JD. Perioperative assessment of myocardial deformation. Anesth Analg. 2014;118 (3):525-44. DOI:10.1213/ANE. 0000000000000088.

41. Stanton T, Leano R, Marwick TH. Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring. Circ Cardiovasc Imaging. 2009;2 (5):356-64. DOI:10.1161/CIRCIMAGING. 109.862334.

42. Mavinkurve-Groothuis AMC, Marcus KA, Pourier M, Loonen J, Feuth T, Hoogerbrugge PM et al. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study. Eur Heart J Cardiovasc Imaging. 2013;14 (6):562-9. DOI:10.1093/ehjci/jes217.

43. Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57 (22):2263-70. DOI:10.1016/j. jacc. 2010.11.063.

44. Toro-Salazar OH, Ferranti J, Lorenzoni R, Walling S, Mazur W, Raman SV et al. Feasibility of echocardiographic techniques to detect subclinical cancer therapeutics-related cardiac dysfunction among high-dose patients when compared with cardiac magnetic resonance imaging. J Am Soc Echocardiogr. 2016;29 (2):119-31. DOI:10.1016/j. echo. 2015.10.008.