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Патогенетическая терапия хронической сердечной недостаточности: позиция торасемида
Патогенетическая терапия хронической сердечной недостаточности: позиция торасемида
Перепеч Н.Б. Патогенетическая терапия хронической сердечной недостаточности: позиция торасемида. Системные гипертензии. 2015; 12 (3): 56–62.
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Аннотация
В статье обсуждаются специфические особенности фармакокинетики торасемида, выгодно отличающие его от фуросемида. Обращается внимание на то, что торасемид обладает антиальдостероновым и антифибротическим эффектом, не свойственным другим диуретикам. Приводятся результаты клинических исследований, в которых была показана способность торасемида препятствовать развитию и вызывать регресс миокардиального фиброза. С учетом современных представлений о патогенезе хронической сердечной недостаточности, в частности месте диастолической дисфункции в развитии нарушений гемодинамики, обосновывается применение торасемида в составе комплексной фармакотерапии хронической сердечной недостаточности у пациентов с высоким давлением наполнения левого желудочка до появления клинических признаков застоя.
Ключевые слова: торасемид, хроническая сердечная недостаточность, диастолическая дисфункция, фиброз миокарда.
Key words: torasemide, chronic heart failure, diastolic dysfunction, myocardial fibrosis.
Ключевые слова: торасемид, хроническая сердечная недостаточность, диастолическая дисфункция, фиброз миокарда.
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Key words: torasemide, chronic heart failure, diastolic dysfunction, myocardial fibrosis.
Полный текст
Список литературы
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8. Vargo DL, Kramer WG, Black PK et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torasemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther 1995; 57: 601–9.
9. Brater DC. Diuretic therapy. N Engl J Med 1998; 339 (6): 387–95.
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14. Goodfriend TL, Ball DL, Oelkers W et al. Torasemide inhibits aldosterone secretion in vitro. Life Sci 1998; 63: 97–105.
15. Lopez B, Querejeta R, Gonzalez A et al. Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardiol 2004; 43 (11): 2028–35.
16. Lopez B, Gonzalez A, Beaumont J et al. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol 2007; 50 (9): 859–67.
17. Veeraveedu PT, Watanabe K, Ma M et al. Comparative effects of torasemide and furosemide in rats with heart failure. Biochem Pharmacol 2007; 23: 143–8.
18. Агеев Ф.Т., Жубрина Е.С., Гиляревский С.Р. и др. Сравнительная эффективность и безопасность длительного применения торасемида у больных с компенсированной сердечной недостаточностью. Влияние на маркеры фиброза миокарда. Сердечная недостаточность. 2013; 14 (2): 55–62. / Ageev F.T., Zhubrina E.S., Giliarevskii S.R. i dr. Sravnitel'naia effektivnost' i bezopasnost' dlitel'nogo primeneniia torasemida u bol'nykh s kompensirovannoi serdechnoi nedostatochnost'iu. Vliianie na markery fibroza miokarda. Serdechnaia nedostatochnost'. 2013; 14 (2): 55–62. [in Russian]
19. The TORAFIC Investigators Group. Effects of Prolonged-Release Torasemide Versus Furosemide on Myocardial Fibrosis in Hypertensive Patients with Chronic Heart Failure: A Randomized, Blinded-End Point, Active-Controlled Study. ClinTher 2011; 33 (9): 1204–13.
20. Fortuno A, Muniz P, Ravassa S. Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. Hypertension 1999; 34: 138–43.
21. Harada K, Izawa H, Nishizawa T et al. Beneficial effects of torasemide on systolic wall stress and sympathetic nervous activity in asymptomatic or mildly symptomatic patients with heart failure: comparison with azosemide. J Cardiovasc Pharmacol 2009; 53 (6): 468–73.
22. Kasama S, Toyama T, Hatori T et al. Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with congestive heart failure. Heart 2006; 92: 1434–40.
23. Noe LL, Vreeland MG, Pezzella SM, Trotter JP. A pharmacoenomic аssessment of torasemide and furosemide in the treatment of patients with congestive heart failure. Clin Ther 1999; 21 (5): 854–6.
24. Murray M, Deer M, Ferguson J et al. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med 2001; 111 (7): 513–20.
25. Spannheimer A, Muller K, Falkenstein P et al. Long-term diuretic treatment in heart failure: are there differences between furosemide end torasemide? Schweiz Rundsch Med Prax 2002; 91 (37): 1467–75.
26. Muller K, Gamba G, Jaquet F, Hess B. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV – efficacy and quality life. J Heart Fail 2003; 5 (6): 793–801.
27. Yamato M, Sasaki T, Honda M et al. Effects of torasemide on left ventricular function and neurohumoral factors in patients with chronic heart failure. Circulat J 2003; 67 (5): 384–90.
28. Cosin J, Diez J, TORIC Investigators. Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail 2002; 4 (4): 507–13.
29. Мареев В.Ю., Выгодин В.А., Беленков Ю.Н. Диyретическая терапия Эффективными дозами пероральных диуретиков торасемида (диувера) и фуросемида в лечении больных с обострением Хронической Сердечной Недостаточности (ДУЭЛЬ-ХСН). Сердечная недостаточность. 2011; 12 (3): 3–10. / Mareev V.Iu., Vygodin V.A., Belenkov Iu.N. Diyreticheskaia terapiia Effektivnymi dozami peroral'nykh diuretikov torasemida (diuvera) i furosemida v lechenii bol'nykh s obostreniem Khronicheskoi Serdechnoi Nedostatochnosti (DUEL''-KhSN). Serdechnaia nedostatochnost'. 2011; 12 (3): 3–10. [in Russian]
30. Беркинбаев С.Ф., Джунусбекова Г.А., Исабекова А.Х. Клиническая эффективность петлевого диуретика торасемида в лечении больных хронической сердечной недостаточностью. Результаты казахстанского многоцентрового исследования «ПОЭТ». Рациональная фармакотерапия в кардиологии. 2014; 10 (5): 495–9. / Berkinbaev S.F., Dzhunusbekova G.A., Isabekova A.Kh. Klinicheskaia effektivnost' petlevogo diuretika torasemida v lechenii bol'nykh khronicheskoi serdechnoi nedostatochnost'iu. Rezul'taty kazakhstanskogo mnogotsentrovogo issledovaniia «POET». Ratsional'naia farmakoterapiia v kardiologii. 2014; 10 (5): 495–9. [in Russian]
31. O’Hanlon R, Grasso M, Roughton M et al. Prognostic signifance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 2010; 56 (11): 867–74.
32. Nagueh SF, Appleton CP, Gillebert TC et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocard 2009; 10 (2): 165–93.
2. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA Guidelines for the Management of Heart Failure. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American College of Chest Physicians, Heart Rhythm Society and International Society for Heart and Lung transplantation. Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation. J Am Coll Cardiol 2013; 62 (16): e147–239.
3. Mareev V.Iu., Ageev F.T., Arutiunov G.P. i dr. Natsional'nye rekomendatsii OSSN, RKO i RNMOT po diagnostike i lecheniiu khronicheskoi serdechnoi nedostatochnosti (chetvertyi peresmotr). Serdechnaia nedostatochnost'. 2013; 14 (7): 379–472. [in Russian]
4. Owan TE, Hodge DO, Herges RM et al. Trends in prevalence and outcome of heart failure with рreserved ejection fraction. N Engl J Med 2006; 355: 251–9.
5. Mareev V.Iu., Danielian M.O., Belenkov Iu.N. Sravnitel'naia kharakteristika bol'nykh s KhSN v zavisimosti ot velichiny FV po rezul'tatam Rossiiskogo mnogotsentrovogo issledovaniia EPOKhA-O-KhSN. Serdechnaia nedostatochnost'. 2006; 7 (4): 164–71. [in Russian]
6. Mc Crindle II, Wa TC, Barron W et al. Effects of food on the absorbtion of furosemide and bumetanide in man. Br J Clin Pharmacol 1996; 42: 743–6.
7. Murray MD, Haag KM, Blak PK et al. Variable furosemide absorption and poor predictability of response in elderly patients. Pharmacotherapy 1997; 17: 98–106.
8. Vargo DL, Kramer WG, Black PK et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torasemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther 1995; 57: 601–9.
9. Brater DC. Diuretic therapy. N Engl J Med 1998; 339 (6): 387–95.
10. Metelitsa VI. Spravochnik po klinicheskoi farmakologii serdechno-sosudistykh lekarstvennykh sredstv. 3-e izd. M., 2005. [in Russian]
11. Bolke T, Achhammer I. Torasemide: review of its pharmacology and therapeutic use. Drugs Today 1994; 8: 1–28.
12. Tkacheva O.N., Sharashkina N.V., Novikova I.M. i dr. Primenenie petlevogo diuretika torasemida v kombinirovannom lechenii gipertonicheskoi bolezni u zhenshchin v period postmenopauzy. Consilium Medicum. 2011; 13 (10): 54–9. [in Russian]
13. Uchida T, Yananaga K, Nishikawa M et al. Anti-aldosteronergic effect of torasemide. Eur J Pharmacol 1991; 205: 145–50.
14. Goodfriend TL, Ball DL, Oelkers W et al. Torasemide inhibits aldosterone secretion in vitro. Life Sci 1998; 63: 97–105.
15. Lopez B, Querejeta R, Gonzalez A et al. Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardiol 2004; 43 (11): 2028–35.
16. Lopez B, Gonzalez A, Beaumont J et al. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol 2007; 50 (9): 859–67.
17. Veeraveedu PT, Watanabe K, Ma M et al. Comparative effects of torasemide and furosemide in rats with heart failure. Biochem Pharmacol 2007; 23: 143–8.
18. Ageev F.T., Zhubrina E.S., Giliarevskii S.R. i dr. Sravnitel'naia effektivnost' i bezopasnost' dlitel'nogo primeneniia torasemida u bol'nykh s kompensirovannoi serdechnoi nedostatochnost'iu. Vliianie na markery fibroza miokarda. Serdechnaia nedostatochnost'. 2013; 14 (2): 55–62. [in Russian]
19. The TORAFIC Investigators Group. Effects of Prolonged-Release Torasemide Versus Furosemide on Myocardial Fibrosis in Hypertensive Patients with Chronic Heart Failure: A Randomized, Blinded-End Point, Active-Controlled Study. ClinTher 2011; 33 (9): 1204–13.
20. Fortuno A, Muniz P, Ravassa S. Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. Hypertension 1999; 34: 138–43.
21. Harada K, Izawa H, Nishizawa T et al. Beneficial effects of torasemide on systolic wall stress and sympathetic nervous activity in asymptomatic or mildly symptomatic patients with heart failure: comparison with azosemide. J Cardiovasc Pharmacol 2009; 53 (6): 468–73.
22. Kasama S, Toyama T, Hatori T et al. Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with congestive heart failure. Heart 2006; 92: 1434–40.
23. Noe LL, Vreeland MG, Pezzella SM, Trotter JP. A pharmacoenomic аssessment of torasemide and furosemide in the treatment of patients with congestive heart failure. Clin Ther 1999; 21 (5): 854–6.
24. Murray M, Deer M, Ferguson J et al. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med 2001; 111 (7): 513–20.
25. Spannheimer A, Muller K, Falkenstein P et al. Long-term diuretic treatment in heart failure: are there differences between furosemide end torasemide? Schweiz Rundsch Med Prax 2002; 91 (37): 1467–75.
26. Muller K, Gamba G, Jaquet F, Hess B. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV – efficacy and quality life. J Heart Fail 2003; 5 (6): 793–801.
27. Yamato M, Sasaki T, Honda M et al. Effects of torasemide on left ventricular function and neurohumoral factors in patients with chronic heart failure. Circulat J 2003; 67 (5): 384–90.
28. Cosin J, Diez J, TORIC Investigators. Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail 2002; 4 (4): 507–13.
29. Mareev V.Iu., Vygodin V.A., Belenkov Iu.N. Diyreticheskaia terapiia Effektivnymi dozami peroral'nykh diuretikov torasemida (diuvera) i furosemida v lechenii bol'nykh s obostreniem Khronicheskoi Serdechnoi Nedostatochnosti (DUEL''-KhSN). Serdechnaia nedostatochnost'. 2011; 12 (3): 3–10. [in Russian]
30. Berkinbaev S.F., Dzhunusbekova G.A., Isabekova A.Kh. Klinicheskaia effektivnost' petlevogo diuretika torasemida v lechenii bol'nykh khronicheskoi serdechnoi nedostatochnost'iu. Rezul'taty kazakhstanskogo mnogotsentrovogo issledovaniia «POET». Ratsional'naia farmakoterapiia v kardiologii. 2014; 10 (5): 495–9. [in Russian]
31. O’Hanlon R, Grasso M, Roughton M et al. Prognostic signifance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 2010; 56 (11): 867–74.
32. Nagueh SF, Appleton CP, Gillebert TC et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocard 2009; 10 (2): 165–93.
2. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA Guidelines for the Management of Heart Failure. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American College of Chest Physicians, Heart Rhythm Society and International Society for Heart and Lung transplantation. Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation. J Am Coll Cardiol 2013; 62 (16): e147–239.
3. Мареев В.Ю., Агеев Ф.Т., Арутюнов Г.П. и др. Национальные рекомендации ОССН, РКО и РНМОТ по диагностике и лечению хронической сердечной недостаточности (четвертый пересмотр). Сердечная недостаточность. 2013; 14 (7): 379–472. / Mareev V.Iu., Ageev F.T., Arutiunov G.P. i dr. Natsional'nye rekomendatsii OSSN, RKO i RNMOT po diagnostike i lecheniiu khronicheskoi serdechnoi nedostatochnosti (chetvertyi peresmotr). Serdechnaia nedostatochnost'. 2013; 14 (7): 379–472. [in Russian]
4. Owan TE, Hodge DO, Herges RM et al. Trends in prevalence and outcome of heart failure with рreserved ejection fraction. N Engl J Med 2006; 355: 251–9.
5. Мареев В.Ю., Даниелян М.О., Беленков Ю.Н. Сравнительная характеристика больных с ХСН в зависимости от величины ФВ по результатам Российского многоцентрового исследования ЭПОХА-О-ХСН. Сердечная недостаточность. 2006; 7 (4): 164–71. / Mareev V.Iu., Danielian M.O., Belenkov Iu.N. Sravnitel'naia kharakteristika bol'nykh s KhSN v zavisimosti ot velichiny FV po rezul'tatam Rossiiskogo mnogotsentrovogo issledovaniia EPOKhA-O-KhSN. Serdechnaia nedostatochnost'. 2006; 7 (4): 164–71. [in Russian]
6. Mc Crindle II, Wa TC, Barron W et al. Effects of food on the absorbtion of furosemide and bumetanide in man. Br J Clin Pharmacol 1996; 42: 743–6.
7. Murray MD, Haag KM, Blak PK et al. Variable furosemide absorption and poor predictability of response in elderly patients. Pharmacotherapy 1997; 17: 98–106.
8. Vargo DL, Kramer WG, Black PK et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torasemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther 1995; 57: 601–9.
9. Brater DC. Diuretic therapy. N Engl J Med 1998; 339 (6): 387–95.
10. Метелица ВИ. Справочник по клинической фармакологии сердечно-сосудистых лекарственных средств. 3-е изд. М., 2005. / Metelitsa VI. Spravochnik po klinicheskoi farmakologii serdechno-sosudistykh lekarstvennykh sredstv. 3-e izd. M., 2005. [in Russian]
11. Bolke T, Achhammer I. Torasemide: review of its pharmacology and therapeutic use. Drugs Today 1994; 8: 1–28.
12. Ткачева О.Н., Шарашкина Н.В., Новикова И.М. и др. Применение петлевого диуретика торасемида в комбинированном лечении гипертонической болезни у женщин в период постменопаузы. Consilium Medicum. 2011; 13 (10): 54–9. / Tkacheva O.N., Sharashkina N.V., Novikova I.M. i dr. Primenenie petlevogo diuretika torasemida v kombinirovannom lechenii gipertonicheskoi bolezni u zhenshchin v period postmenopauzy. Consilium Medicum. 2011; 13 (10): 54–9. [in Russian]
13. Uchida T, Yananaga K, Nishikawa M et al. Anti-aldosteronergic effect of torasemide. Eur J Pharmacol 1991; 205: 145–50.
14. Goodfriend TL, Ball DL, Oelkers W et al. Torasemide inhibits aldosterone secretion in vitro. Life Sci 1998; 63: 97–105.
15. Lopez B, Querejeta R, Gonzalez A et al. Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardiol 2004; 43 (11): 2028–35.
16. Lopez B, Gonzalez A, Beaumont J et al. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol 2007; 50 (9): 859–67.
17. Veeraveedu PT, Watanabe K, Ma M et al. Comparative effects of torasemide and furosemide in rats with heart failure. Biochem Pharmacol 2007; 23: 143–8.
18. Агеев Ф.Т., Жубрина Е.С., Гиляревский С.Р. и др. Сравнительная эффективность и безопасность длительного применения торасемида у больных с компенсированной сердечной недостаточностью. Влияние на маркеры фиброза миокарда. Сердечная недостаточность. 2013; 14 (2): 55–62. / Ageev F.T., Zhubrina E.S., Giliarevskii S.R. i dr. Sravnitel'naia effektivnost' i bezopasnost' dlitel'nogo primeneniia torasemida u bol'nykh s kompensirovannoi serdechnoi nedostatochnost'iu. Vliianie na markery fibroza miokarda. Serdechnaia nedostatochnost'. 2013; 14 (2): 55–62. [in Russian]
19. The TORAFIC Investigators Group. Effects of Prolonged-Release Torasemide Versus Furosemide on Myocardial Fibrosis in Hypertensive Patients with Chronic Heart Failure: A Randomized, Blinded-End Point, Active-Controlled Study. ClinTher 2011; 33 (9): 1204–13.
20. Fortuno A, Muniz P, Ravassa S. Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. Hypertension 1999; 34: 138–43.
21. Harada K, Izawa H, Nishizawa T et al. Beneficial effects of torasemide on systolic wall stress and sympathetic nervous activity in asymptomatic or mildly symptomatic patients with heart failure: comparison with azosemide. J Cardiovasc Pharmacol 2009; 53 (6): 468–73.
22. Kasama S, Toyama T, Hatori T et al. Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with congestive heart failure. Heart 2006; 92: 1434–40.
23. Noe LL, Vreeland MG, Pezzella SM, Trotter JP. A pharmacoenomic аssessment of torasemide and furosemide in the treatment of patients with congestive heart failure. Clin Ther 1999; 21 (5): 854–6.
24. Murray M, Deer M, Ferguson J et al. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med 2001; 111 (7): 513–20.
25. Spannheimer A, Muller K, Falkenstein P et al. Long-term diuretic treatment in heart failure: are there differences between furosemide end torasemide? Schweiz Rundsch Med Prax 2002; 91 (37): 1467–75.
26. Muller K, Gamba G, Jaquet F, Hess B. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV – efficacy and quality life. J Heart Fail 2003; 5 (6): 793–801.
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24. Murray M, Deer M, Ferguson J et al. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med 2001; 111 (7): 513–20.
25. Spannheimer A, Muller K, Falkenstein P et al. Long-term diuretic treatment in heart failure: are there differences between furosemide end torasemide? Schweiz Rundsch Med Prax 2002; 91 (37): 1467–75.
26. Muller K, Gamba G, Jaquet F, Hess B. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV – efficacy and quality life. J Heart Fail 2003; 5 (6): 793–801.
27. Yamato M, Sasaki T, Honda M et al. Effects of torasemide on left ventricular function and neurohumoral factors in patients with chronic heart failure. Circulat J 2003; 67 (5): 384–90.
28. Cosin J, Diez J, TORIC Investigators. Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail 2002; 4 (4): 507–13.
29. Mareev V.Iu., Vygodin V.A., Belenkov Iu.N. Diyreticheskaia terapiia Effektivnymi dozami peroral'nykh diuretikov torasemida (diuvera) i furosemida v lechenii bol'nykh s obostreniem Khronicheskoi Serdechnoi Nedostatochnosti (DUEL''-KhSN). Serdechnaia nedostatochnost'. 2011; 12 (3): 3–10. [in Russian]
30. Berkinbaev S.F., Dzhunusbekova G.A., Isabekova A.Kh. Klinicheskaia effektivnost' petlevogo diuretika torasemida v lechenii bol'nykh khronicheskoi serdechnoi nedostatochnost'iu. Rezul'taty kazakhstanskogo mnogotsentrovogo issledovaniia «POET». Ratsional'naia farmakoterapiia v kardiologii. 2014; 10 (5): 495–9. [in Russian]
31. O’Hanlon R, Grasso M, Roughton M et al. Prognostic signifance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 2010; 56 (11): 867–74.
32. Nagueh SF, Appleton CP, Gillebert TC et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocard 2009; 10 (2): 165–93.
Авторы
Н.Б.Перепеч
Научно-клинический и образовательный центр «Кардиология» Института высоких медицинских технологий медицинского факультета ФГБОУ ВПО «Санкт-Петербургский государственный университет».
nikita_perepech@mail.ru
Scientific-Clinical and Educational Center "Cardiology" of the Institute of High Medical Technologies of the Faculty of Medicine of the St. Petersburg State University.
nikita_perepech@mail.ru
Научно-клинический и образовательный центр «Кардиология» Института высоких медицинских технологий медицинского факультета ФГБОУ ВПО «Санкт-Петербургский государственный университет».
nikita_perepech@mail.ru
________________________________________________
Scientific-Clinical and Educational Center "Cardiology" of the Institute of High Medical Technologies of the Faculty of Medicine of the St. Petersburg State University.
nikita_perepech@mail.ru
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