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Поиск ранних маркеров кардиотоксичности противоопухолевого лечения у больных раком молочной железы в зависимости от уровня артериального давления
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Avalyan A.A., Kirillova M.Yu., Shitov V.N. et al. Markers of early cardiotoxicity in patients with breast cancer undergoing chemotherapy depending on blood pressure level. Systemic Hypertension. 2017; 14 (3): 21–27. DOI: 10.26442/2075-082X_14.3.21-27
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Материалы и методы. В исследование были включены 70 больных тройным негативным РМЖ (средний возраст 48,6±13,3 года), получавших химиотерапию с включением антрациклинов, таксанов и производных платины (8 курсов). Больным выполнялось ультразвуковое исследование сердца, включая метод недопплеровского изображения миокарда (Speckle Tracking Imaging) в двумерном режиме (2D Strain) до и после 8 курсов химиотерапии. Для оценки глобальной систолической функции ЛЖ определялись фракция выброса левого желудочка (ФВ ЛЖ) (по методу Simpson’s Biplane) и показатель глобального продольного стрейна (глобальная продольная деформация левого желудочка – global longitudinal strain, GLS, по данным метода недопплеровского изображения миокарда в двумерном режиме). Больные были разделены на 2 группы: 1-я группа (n=18) – больные с анамнезом АГ и 2-я группа (n=52) – без анамнеза АГ.
Результаты. Значения показателя GLS до начала курсов химиотерапии в 1-й группе (с АГ) были ниже нормальных значений (-19,1±2,8% vs -22,1±1,8%; p<0,05) и ниже, чем во 2-й группе, без АГ (-20,1±2,8%; p>0,05). После 8 курсов химиотерапии наблюдалось снижение показателя GLS как в общей группе (с -20,0±2,8 до -18,5±2,9%; p<0,05), так и в 1 и 2-й группах: в 1-й группе выявлено снижение с -19,1±2,8 до -16,4±3,8% (р<0,05); во 2-й группе с -20,1±2,8 до -19,2±2,4% (p<0,05). Значения показателя GLS снизились более чем на 15% у 12 (17%) женщин из всех наблюдаемых больных. Несмотря на то, что ФВ ЛЖ снижалась в обеих группах, она находилась в пределах допустимых значений (норма ФВ ЛЖ>55%).
Заключение. GLS по данным метода недопплеровского изображения миокарда (Speckle Tracking Imaging) в двумерном режиме (2D Strain), вероятно, является одним из наиболее ранних маркеров кардиотоксичности, индуцированной химиотерапией, по сравнению с показателем ФВ ЛЖ.
Ключевые слова: кардиоонкология, артериальная гипертония, кардиотоксичность, глобальный продольный стрейн левого желудочка, химиотерапия, рак молочной железы.
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Objective. To study the possibility of the 2D Speckle Tracking Imaging in early detection of cardiotoxicity in patients with triple negative breast cancer and arterial hypertension (AH) during anthracycline-containing chemotherapy.
Materials and methods. 70 women (mean age 48.6±13.3 years) with triple negative breast cancer were enrolled. All patients underwent chemotherapy, including anthracycline, taxan, platinum-based agent. Echocardiography, including 2D Speckle Tracking Imaging, was performed on Vivid-E 9 ultrasound machine before and after 8 weeks of chemotherapy. Left ventricular ejection fraction (LVEF) (the biplane Simpson`s method) and global longitudinal strain (GLS) (mean normal GLS of -22.1±1.8 for women) were analysed. Patients were divided into two groups: group 1 – with AH (n=18) and group 2 – with normal blood pressure (n=52).
Results. Before chemotherapy in group 1 GLS was lower than normal value (-19.1±2.8% vs -22.1±1.8%; p<0.05) and lower than in the group 2 (-19.1±2.8% vs -20.0±2.8%; p>0.05). After chemotherapy in all patients GLS decrease was observed from -20.0±2.8% to -18.5±2.9% (p<0.05) and in group 1 from -19.1±2.8% to -16.4±3.8% (р<0.05), group 2 from -20.0±2.8% to -19.2±2.4% (p<0.05). However LVEF remained within normal values. The values of GLS decreased by more than 15% in 12 (17%) of all the patients.
Conclusions. Apparently, GLS is the one of most sensitive early marker of chemotherapy – induced cardiotoxicity compared with the LVEF.
Key words: cardio-oncology, arterial hypertension, cardiotoxicity, global longitudinal strain of the left ventricle, chemotherapy, breast cancer.
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27. Crawford SC. Acute Chemotherapy-Induced Cardiovascular Changes in Patients With Testicular Cancer: Are There Implications for Blood Pressure Management in Patients Receiving Chemotherapy? J Clin Oncol 2006; 24 (15): 2399–400.
28. Radwan H, Hussein E. Value of global longitudinal strain by two dimensional speckle tracking echocardiography in predicting coronary artery disease severity. Egypt Heart J 2017; 69: 95–101.
29. Stoodley PW, Richards DA, Boyd A et al. Altered left ventricular longitudinal diastolic function correlates with reduced systolic function immediately after anthracycline chemotherapy. Eur Heart J Cardiovasc Imaging 2013; 14 (3): 228–34.
30. Portugal G, Moura Branco L, Galrinho A et al. Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity. Rev Port Cardiol 2017; 36 (1): 9–15.
31. Boyd A, Stoodley P, Richards D et al. Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study. PLoS One 2017; 12 (4): e0175544; 15.
32. Fraeman KH, Nordstrom BL, Luo W et al. Incidence of New-Onset Hypertension in Cancer Patients: A Retrospective Cohort Study. Int J Hypertens 2013. Article ID 379252; 10.
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1. Brana I, Tabernero J. Cardiotoxicity. Ann Oncol 2010; 21: 173–9.
2. Gillespie HS, McGann CJ, Wilson BD. Noninvasive diagnosis of chemotherapy related cardiotoxicity. Curr Cardiol Rev 2011; 7: 234–44.
3. Jensen BV. Cardiotoxic consequences of anthracyline-containing therapy in patients with breast cancer. Semin Oncol 2006; 33: 15–21.
4. Doyle JJ, Neugut AI, Jacobson JS et al. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol 2005; 23: 8597–605.
5. Hooning MJ, Botma A, Aleman BM et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 2007; 99: 365–75.
6. Korneeva O.N., Drapkina O.M., Kozlova E.V. i dr. Kardiomiopatiia, indutsirovannaia polikhimioterapiei, u bol'nykh rakom molochnoi zhelezy. Klinitsist. 2011; 3: 109–11. [in Russian]
7. Shuikova K.V., Emelina E.I., Gendlin G.E. i dr. Kardiotoksichnost' sovremennykh khimioterapevticheskikh preparatov. AtmosferA. Novosti kardiologii. 2012; 3: 9–19. [in Russian]
8. Cardinale D, Colombo A, Lamantia G et al. Anthracycline-induced cardiomyopathy: Clinical relevance and response to pharmacologic therapy. JACC 2010; 55 (3): 213–20.
9. Chazova I.E., Oshchepkova E.V., Kirillova M.Yu., Stenina M.B. Risk of hypertension development in patients with oncological diseases under anticancer treatment. Consilium Medicum. 2016; 18 (1): 16–20. [in Russian]
10. Chazova I.E., Oshchepkova E.V., Kirillova M.Iu. i dr. Serdechno-sosudistye i onkologicheskie zabolevaniia: poisk reshenii novykh problem. Sistemnye gipertenzii. 2015; 12 (2): 6–7. [in Russian]
11. Sadurska E. Current Views on Anthracycline Cardiotoxicity in Childhood Cancer Survivors. Pediatr Cardiol 2015; 36: 1112–9.
12. VOZ. URL: http://www.who.int/ru/ [in Russian]
13. Chazova I.E., Zhernakova Iu.V., Oshchepkova E.V. i dr. Rasprostranennost' faktorov riska serdechno-sosudistykh zabolevanii v rossiiskoi populiatsii bol'nykh arterial'noi gipertoniei. Kardiologiia. 2014; 10: 4–12. [in Russian]
14. Piccirillo JF, Tierney RM, Costas I et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 2004; 291 (20): 2441–7.
15. Sharipova G.Kh., Saidova M.A., Zhernakova Iu.V., Chazova I.E. Vliianie metabolicheskogo sindroma u bol'nykh arterial'noi gipertoniei. Al'manakh klinicheskoi meditsiny. 2015; 1 (Spetsvyp.): 102–10. [in Russian]
16. Erika Matos , Borut Jug, Rok Blagus et al. A Prospective Cohort Study on Cardiotoxicity of Adjuvant Trastuzumab Therapy in Breast Cancer Patients. Arq Bras Cardiol 2016; 107 (1): 40–47.
17. Robin K. Kuriakose, Rakesh C. Kukreja, and Lei Xi Potential. Therapeutic Strategies for Hypertension-Exacerbated Cardiotoxicity of Anticancer Drugs. Oxid Med Cell Longev 2016; Article ID 8139861; 9.
18. Bovelli D, Plataniotis G, Roila F. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann Oncol 2010; 21 (Suppl. 5): 277–82.
19. Seidman A, Hudis C, Pierri MK et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002; 20: 1215–21.
20. Daher IN, Kim C, Saleh RR et al. Prevalence of abnormal echocardiographic findings in cancer patients: a retrospective evaluation of echocardiography for identifying cardiac abnormalities in cancer patients. Echocardiography 2011; 28: 1061–7.
21. 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. J Am Soc Echocardiogr 2014; 27: 911–39.
22. Mondillo S, Galderisi M, Mele D et al. Speckle-Tracking Echocardiography: A New Technique for Assessing Myocardial Function. J Ultrasound Med 2011; 30: 71–8.
23. Zamorano JL, Lancellotti P, Rodriguez Muñoz D et al. 2016 ESC Position Paper on cancer treatment and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J 2016; August 26: 1–34. doi: 10.1093/eurheartj/ehw211
24. Lenihan DJ, Kowey PR. Overview and management of cardiac adverse events associated with tyrosine kinase inhibitors. Oncologist 2013; 18: 900–8.
25. Vasiuk Iu.A., Shkol'nik E.L. i dr. Antratsiklinovaia kardiotoksichnost': perspektivy ispol'zovaniia ivabradina. Cardiosomatics. 2012; 3 (4): 65–9. [in Russian]
26. Mouhayar E, Salahudeen A. Hypertension in cancer patients. Tex Heart Inst J 2011; 38 (3): 263–5.
27. Crawford SC. Acute Chemotherapy-Induced Cardiovascular Changes in Patients With Testicular Cancer: Are There Implications for Blood Pressure Management in Patients Receiving Chemotherapy? J Clin Oncol 2006; 24 (15): 2399–400.
28. Radwan H, Hussein E. Value of global longitudinal strain by two dimensional speckle tracking echocardiography in predicting coronary artery disease severity. Egypt Heart J 2017; 69: 95–101.
29. Stoodley PW, Richards DA, Boyd A et al. Altered left ventricular longitudinal diastolic function correlates with reduced systolic function immediately after anthracycline chemotherapy. Eur Heart J Cardiovasc Imaging 2013; 14 (3): 228–34.
30. Portugal G, Moura Branco L, Galrinho A et al. Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity. Rev Port Cardiol 2017; 36 (1): 9–15.
31. Boyd A, Stoodley P, Richards D et al. Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study. PLoS One 2017; 12 (4): e0175544; 15.
32. Fraeman KH, Nordstrom BL, Luo W et al. Incidence of New-Onset Hypertension in Cancer Patients: A Retrospective Cohort Study. Int J Hypertens 2013. Article ID 379252; 10.
1 Институт клинической кардиологии им. А.Л.Мясникова ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России. 121552, Россия, Москва, ул. 3-я Черепковская, д.15а;
2 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*ani_avalian@mail.ru
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A.A.Avalyan*1, M.Yu.Kirillova1, V.N.Shitov1, Ye.V.Oshchepkova1, M.A.Saidova1, M.B.Stenina2, I.Ye.Chazova1
1 A.L.Myasnikov Institute of Clinical Cardiology National Research Medical Center of Cardiology of the Ministry of Health of the Russian Federation. 121552, Russian Federation, Moscow, ul. 3-ia Cherepkovskaia, d. 15a;
2 N.N.Blokhin National Research Medical Center of Oncology of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*ani_avalian@mail.ru