Достижения современной специфической терапии легочной артериальной и хронической тромбоэмболической легочной гипертензии: фокус на стимулятор растворимой гуанилатциклазы риоцигуат
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Gratsianskaya S.E., Valieva Z.S., Martynyuk T.V. The achievements of the modern specific therapy of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: focus on the stimulator of soluble guanylate cyclase riociguat. Therapeutic Archive. 2020; 92 (9): 77–84. DOI: 10.26442/00403660.2020.09.000717
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Ключевые слова: легочная артериальная гипертензия, хроническая тромбоэмболическая легочная гипертензия, стимуляторы растворимой гуанилатциклазы, риоцигуат.
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Currently, treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is focused on three signaling pathways: the NO pathway, the endothelin pathway, and the prostacyclin pathway. Riociguat is the only representative of stimulators of the soluble guanylate cyclase (sGC) class that is approved for the treatment of PAH and inoperable and persistent/recurrent CTEPH. The review presents data from clinical trials showing a positive effect of riociguat on the functional and hemodynamic profile of patients with PAH and CTEPH. In recent years there has been much discussion about the possibility of optimizing therapy by switching to drugs that affect a single pathogenesis target. Thus, sGC stimulants have obvious advantages over phosphodiesterase type 5 (PDE-5) inhibitors, including the ability of riociguat to exert pharmacological effects (due to a NO-independent mechanism of action) even in conditions of reduced NO production. Switching from PDE-5 to riociguat may be safe and appropriate, according to clinical trials presented in the review. In accordance with the guidelines for the diagnosis and treatment of pulmonary hypertension of the Eurasian Association of cardiologists from 2019, this strategy is approved when PDE5 therapy is ineffective in patients with PAH FC III (WHO).
Keywords: pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, stimulators of the soluble guanylate cyclase, riociguat.
2. Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(Suppl.25):D34-41. doi: 10.1016/j.jacc.2013.10.029
3. Чазова И.Е., Мартынюк Т.В., Валиева З.С. и др. Евразийские клинические рекомендации по диагностике и лечению легочной гипертензии. Евразийский кардиологический журнал. 2020;1:78-122
[Eurasian clinical guidelines on diagnosis and treatment of pulmonary hypertension. Eurasian Heart Journal. 2020;1:78-122 (In Russ.)]. doi: 10.24411/2076-4766-2020-10002
4. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. Circulation. 2009;119(16):2250-94. doi: 10.1161/CIRCULATIONAHA
5. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119. doi: 10.1183/13993003.01032-2015
6. Montani D, Chaumais MC, Guignabert C, et al. Targeted therapies in pulmonary arterial hypertension. Pharmacol Ther. 2014;141(2):172-91. doi: 10.1016/j.pharmthera.2013.10.002
7. Schermuly RT, Stasch JP, Pullamsetti SS, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008;32:881-91. doi: 10.1183/09031936.00114407
8. Мартынюк Т.В. Ингаляционный оксид азота, ингибиторы фосфодиэстеразы типа 5, стимуляторы гуанилатциклазы. В кн.: Легочная гипертензия. Под ред. И.Е. Чазовой, Т.В. Мартынюк. М.: Практика, 2015; с. 766-810 [Martynyuk TV. Inhaled nitric oxide, phosphodiesterase type 5 inhibitors, guanylate cyclase stimulants. Book: Pulmonary hypertension. In: Chazova IE, Martynyuk TV. Moscow: Praktika, 2015; p. 766-810 (In Russ.)].
9. Galiè N, Ghofrani HA, Torbicki А, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148-57.
10. Валиева З.С., Таран И.Н., Мартынюк Т.В., Чазова И.Е. Современный взгляд на место риоцигуата в лечении легочной гипертензии. Терапевтический архив. 2018;90(4):55-9 [Valieva ZS, Taran IN, Martynyuk TV, Chazova IYe. Modern view on the place of riociguat in the treatment of pulmonary hypertension. Therapeutic Archive. 2018;90(4):55-9 (In Russ.)]. doi: 10.26442/terarkh201890455-59
11. Brown Т. FDA Panel Recommends Riociguat (Adempas) for 2 Pulmonary Hypertension Indications. 2013. https://www.medscape.com/viewarticle/809083
12. Инструкция по медицинскому применению препарата Адемпас. Регистрационный номер: ЛП-002639 (версия от 10.10.2019). Государственный реестр лекарственных средств [Instructions for the medical use of the drug Adempas. Registration number: ЛП-002639 (version dated 10.10.2019). State Register of Medicines (In Russ.)]. https://grls.rosminzdrav.ru
13. Ghofrani HA, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330-40. doi: 10.1056/NEJMoa1209655
14. Rubin LJ, et al. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015;45:1303-13. doi: 10.1183/09031936.00090614
15. Ghofrani HF, Grimminger F, Grünig E, et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open label, randomised, long-term extension trial. Lancet Respir Med. 2016;4(5):361-71. doi: 10.1016/S2213-2600(16)30019-4
16. Rosenkranz S, Ghofrani HA, Beghetti M, et al. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart. 2015;101(22):1792-9. doi: 10.1136/heartjnl-2015-307832
17. Sood N, Aranda A, Platt D, et al. Riociguat improves health-related quality of life for patients with pulmonary arterial hypertension: results from the phase 4 MOTION study. Pulm Circ. 2019;9(1):2045894018823715. doi: 10.1177/2045894018823715
18. Jungmann NA, Lang D, Saleh S, et al. In vitro-in vivo correlation of the drug-drug interaction potential of antiretroviral HIV treatment regimens on CYP1A1substrate riociguat. Expert Opin Drug Metab Toxicol. 2019;15(11):975-84. doi: 10.1080/17425255.2019.1681968
19. Ghofrani HA, et al. Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension. N Engl J Med. 2013;369:319-29. doi: 10.1056/NEJMoa1209657
20. Simonneau G, D'Armini AM, Ghofrani HA, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J. 2015;45(5):1293-302. doi: 10.1183/09031936.00087114
21. McLaughlin VV, Jansa P, Nielsen-Kudsk JE, et al. Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study. BMC Pulm Med. 2017;17(1):216. doi: 10.1186/s12890-017-0563-7
22. Van Thor MCJ, Ten Klooster L, Snijder RJ, et al. Long-term clinical value and outcome of riociguat in chronic thromboembolic pulmonary hypertension. Int J Cardiol Heart Vasc. 2019;22:163-8. doi: 10.1016/j.ijcha.2019.02.004
23. Jansa P, Ambroz D, Kuchar J, et al. The impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension – results of a retrospective clinical registry. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020. doi: 10.5507/bp.2019.061
24. Tsai CH, Wu CK, Kuo PH, et al. Riociguat Improves Pulmonary Hemodynamics in Patients with Inoperable Chronic Thromboembolic Pulmonary Hypertension. Acta Cardiol Sin. 2020;36(1):64-71. doi: 10.6515/ACS.202001_36(1).20190612A
25. Yamamoto K, Nishimura R, Kato F, et al. Protective role of endothelial progenitor cells stimulated by riociguat in chronic thromboembolic pulmonary hypertension. Int J Cardiol. 2020;299:263-70. doi: 10.1016/
j.ijcard.2019.07.017
26. Чазова И.Е., Валиева З.С., Наконечников С.Н. и др. Сравнительный анализ клинического, функционального, гемодинамического профиля пациентов с неоперабельной хронической тромбоэмболической и идиопатической легочной гипертензией по данным Российского регистра. Терапевтический архив. 2018;90(10):
63-73 [Chazova IE, Valieva ZS, Nakonechnikov SN, et al. Features of clinical, functional and hemodynamics profile, medical treatment and prognosis evaluation in patients with inoperable chronic thromboembolic pulmonary hypertension and idiopathic pulmonary
arterial hypertension according to the Russian registry. Therapeutic Archive. 2018;90(10):63-73 (In Russ.)]. doi: 10.26442/00403660.
2019.09.000343
27. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53:1801889. doi: 10.1183/13993003.01889-2018
28. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50:1700889. doi: 10.1183/13993003.00889-2017
29. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50:1700740. doi: 10.1183/13993003.00740-2017
30. Kylhammar D, Kjellstrom B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39:4175–81. doi: 10.1093/eurheartj/ehx257
31. Humbert M, Farber HW, Ghofrani HA, et al. Risk assessment in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Eur Respir J. 2019;53(6):1802004. doi: 10.1183/13993003.02004-2018
32. Marra AM, Halank M, Benjamin N, et al. Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study). Respir Res. 2018;19(1):258. doi: 10.1186/s12931-018-0957-y
33. Leon-Velarde F, Maggiorini M, Reeves JT, et al. Consensus statement on chronic and subacute high altitude diseases. High Alt Med Biol. 2005;6:147-57. doi: 10.1089/ham.2005.6.147
34. Hoeper MM, et al. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur Respir J. 2017;50(3):1602425. doi: 10.1183/13993003.02425-2016
35. Gall H, Vachiéry JL, Tanabe N, et al. Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH. Lung. 2018;196:305-12. doi: 10.1007/s00408-018-0100-3
36. Yamamoto K, Tanabe N, Suda R, et al. Riociguat for patients with chronic thromboembolic pulmonary hypertension: Usefulness of transitioning from phosphodiesterase type 5 inhibitor. Respir Investig. 2017;55(4):270-5. doi: 10.1016/j.resinv.2017.04.004
37. Darocha S, Banaszkiewicz M, Pietrasik A, et al. Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics. Int J Cardiol. 2018;269:283-8. doi: 10.1016/j.ijcard.2018.07.015
38. Kuroda K, Akagi S, Nakamura K, et al. Successful Transition From Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study. Heart Lung Circ. 2020;29(3):331-6. doi: 10.1016/j.hlc.2019.01.013
39. Taran IN, Belevskaya AA, Saidova MA, et al. Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular-Pulmonary Arterial Coupling. Lung. 2018;196(6):745-53. doi: 10.1007/s00408-018-0160-4
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1. Martynyuk TV. Pulmonary hypertension: diagnostics and treatment. Moscow: Medical informational agency. 2018 (In Russ.)
2. Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(Suppl.25):D34-41. doi: 10.1016/j.jacc.2013.10.029
3. Eurasian clinical guidelines on diagnosis and treatment of pulmonary hypertension. Eurasian Heart Journal. 2020;1:78-122 (In Russ.) doi: 10.24411/2076-4766-2020-10002
4. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. Circulation. 2009;119(16):2250-94. doi: 10.1161/CIRCULATIONAHA
5. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119. doi: 10.1183/13993003.01032-2015
6. Montani D, Chaumais MC, Guignabert C, et al. Targeted therapies in pulmonary arterial hypertension. Pharmacol Ther. 2014;141(2):172-91. doi: 10.1016/j.pharmthera.2013.10.002
7. Schermuly RT, Stasch JP, Pullamsetti SS, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008;32:881-91. doi: 10.1183/09031936.00114407
8. Martynyuk TV. Inhaled nitric oxide, phosphodiesterase type 5 inhibitors, guanylate cyclase stimulants. Book: Pulmonary hypertension. In: Chazova IE, Martynyuk TV. Moscow: Praktika, 2015; p. 766-810 (In Russ.)
9. Galiè N, Ghofrani HA, Torbicki А, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148-57.
10. Valieva ZS, Taran IN, Martynyuk TV, Chazova IYe. Modern view on the place of riociguat in the treatment of pulmonary hypertension. Therapeutic Archive. 2018;90(4):55-9 (In Russ.) doi: 10.26442/terarkh201890455-59
11. Brown Т. FDA Panel Recommends Riociguat (Adempas) for 2 Pulmonary Hypertension Indications. 2013. https://www.medscape.com/viewarticle/809083
12. Instructions for the medical use of the drug Adempas. Registration number: ЛП-002639 (version dated 10.10.2019). State Register of Medicines (In Russ.)
https://grls.rosminzdrav.ru
13. Ghofrani HA, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330-40. doi: 10.1056/NEJMoa1209655
14. Rubin LJ, et al. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015;45:1303-13. doi: 10.1183/09031936.00090614
15. Ghofrani HF, Grimminger F, Grünig E, et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open label, randomised, long-term extension trial. Lancet Respir Med. 2016;4(5):361-71. doi: 10.1016/S2213-2600(16)30019-4
16. Rosenkranz S, Ghofrani HA, Beghetti M, et al. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart. 2015;101(22):1792-9. doi: 10.1136/heartjnl-2015-307832
17. Sood N, Aranda A, Platt D, et al. Riociguat improves health-related quality of life for patients with pulmonary arterial hypertension: results from the phase 4 MOTION study. Pulm Circ. 2019;9(1):2045894018823715. doi: 10.1177/2045894018823715
18. Jungmann NA, Lang D, Saleh S, et al. In vitro-in vivo correlation of the drug-drug interaction potential of antiretroviral HIV treatment regimens on CYP1A1substrate riociguat. Expert Opin Drug Metab Toxicol. 2019;15(11):975-84. doi: 10.1080/17425255.2019.1681968
19. Ghofrani HA, et al. Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension. N Engl J Med. 2013;369:319-29. doi: 10.1056/NEJMoa1209657
20. Simonneau G, D'Armini AM, Ghofrani HA, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J. 2015;45(5):1293-302. doi: 10.1183/09031936.00087114
21. McLaughlin VV, Jansa P, Nielsen-Kudsk JE, et al. Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study. BMC Pulm Med. 2017;17(1):216. doi: 10.1186/s12890-017-0563-7
22. Van Thor MCJ, Ten Klooster L, Snijder RJ, et al. Long-term clinical value and outcome of riociguat in chronic thromboembolic pulmonary hypertension. Int J Cardiol Heart Vasc. 2019;22:163-8. doi: 10.1016/j.ijcha.2019.02.004
23. Jansa P, Ambroz D, Kuchar J, et al. The impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension – results of a retrospective clinical registry. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020. doi: 10.5507/bp.2019.061
24. Tsai CH, Wu CK, Kuo PH, et al. Riociguat Improves Pulmonary Hemodynamics in Patients with Inoperable Chronic Thromboembolic Pulmonary Hypertension. Acta Cardiol Sin. 2020;36(1):64-71. doi: 10.6515/ACS.202001_36(1).20190612A
25. Yamamoto K, Nishimura R, Kato F, et al. Protective role of endothelial progenitor cells stimulated by riociguat in chronic thromboembolic pulmonary hypertension. Int J Cardiol. 2020;299:263-70. doi: 10.1016/
j.ijcard.2019.07.017
26. Chazova IE, Valieva ZS, Nakonechnikov SN, et al. Features of clinical, functional and hemodynamics profile, medical treatment and prognosis evaluation in patients with inoperable chronic thromboembolic pulmonary hypertension and idiopathic pulmonary
arterial hypertension according to the Russian registry. Therapeutic Archive. 2018;90(10):63-73 (In Russ.) doi: 10.26442/00403660.
2019.09.000343
27. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53:1801889. doi: 10.1183/13993003.01889-2018
28. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50:1700889. doi: 10.1183/13993003.00889-2017
29. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50:1700740. doi: 10.1183/13993003.00740-2017
30. Kylhammar D, Kjellstrom B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39:4175–81. doi: 10.1093/eurheartj/ehx257
31. Humbert M, Farber HW, Ghofrani HA, et al. Risk assessment in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Eur Respir J. 2019;53(6):1802004. doi: 10.1183/13993003.02004-2018
32. Marra AM, Halank M, Benjamin N, et al. Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study). Respir Res. 2018;19(1):258. doi: 10.1186/s12931-018-0957-y
33. Leon-Velarde F, Maggiorini M, Reeves JT, et al. Consensus statement on chronic and subacute high altitude diseases. High Alt Med Biol. 2005;6:147-57. doi: 10.1089/ham.2005.6.147
34. Hoeper MM, et al. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur Respir J. 2017;50(3):1602425. doi: 10.1183/13993003.02425-2016
35. Gall H, Vachiéry JL, Tanabe N, et al. Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH. Lung. 2018;196:305-12. doi: 10.1007/s00408-018-0100-3
36. Yamamoto K, Tanabe N, Suda R, et al. Riociguat for patients with chronic thromboembolic pulmonary hypertension: Usefulness of transitioning from phosphodiesterase type 5 inhibitor. Respir Investig. 2017;55(4):270-5. doi: 10.1016/j.resinv.2017.04.004
37. Darocha S, Banaszkiewicz M, Pietrasik A, et al. Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics. Int J Cardiol. 2018;269:283-8. doi: 10.1016/j.ijcard.2018.07.015
38. Kuroda K, Akagi S, Nakamura K, et al. Successful Transition From Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study. Heart Lung Circ. 2020;29(3):331-6. doi: 10.1016/j.hlc.2019.01.013
39. Taran IN, Belevskaya AA, Saidova MA, et al. Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular-Pulmonary Arterial Coupling. Lung. 2018;196(6):745-53. doi: 10.1007/s00408-018-0160-4
1 Институт клинической кардиологии им. А.Л. Мясникова ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
________________________________________________
S.E. Gratsianskaya1, Z.S. Valieva1, T.V. Martynyuk1,2
1 Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia