Легочная артериальная гипертензия: достижения и реалии современного лечения, взгляд в будущее

1. 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 [Chazova IE, Martynyuk TV, Valieva ZS, et al. Eurasian Guidelines for the diagnosis and treatment of pulmonary hypertension. Eurasian Нeart Journal. 2020;1:78-122 (in Russian)]. DOI:10.38109/2225-1685-2020-1-78-122
2. Galiè 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;37:67-119. DOI:10.1183/13993003.01032-2015
3. D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med. 1991;115:343-9. DOI:10.7326/0003-4819-115-5-343
4. Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142:448-56. DOI:10.1378/chest.11-1460
5. Чазова И.Е., Архипова О.А., Валиева З.С., и др. Легочная гипертензия в России: первые результаты национального регистра. Терапевтический архив. 2014;86(9):56-64 [Chazova IE, Arkhipova OA, Valieva ZS, et al. Pulmonary hypertension in Russia: the first results of the National Registry. Terapevticheskii Arkhiv (Ter. Arkh.). 2014;86(9):56-64 (in Russian)]. DOI:10.26442/00403660.2019.01.000024
6. Chazova I, Martynyuk T, Valieva Z, et al. Clinical and instrumental characteristics of newly diagnosed patients with various forms of pulmonary hypertension according to the Russian National Registry. BioMed Research International. 2020. Article ID 6836973. DOI:10.1155/2020/6836973
7. Мартынюк Т.В. Легочная гипертензия: Диагностика и лечение. Серия: Библиотека ФГБУ «НИМЦ кардиологии» Минздрава России. М.: Медицинское информационное агентство. 2018 [Martyniuk TV. Pulmonary Hypertension: Diagnosis and Treatment. Series: Library of the Federal State Budgetary Institution “NIMC of Cardiology” of the Ministry of Health of Russia. Moscow: Meditsinskoe informatsionnoe agentstvo. 2018 (in Russian)].
8. Мартынюк Т.В., Наконечников С.Н., Чазова И.Е. Новые горизонты применения антагониста рецепторов эндотелина второго поколения мацитентана у пациентов с легочной гипертензией. Терапевтический архив. 2018;90(4):72-80 [Martynyuk TV, Nakonechnikov SN, Chazova IE. New horizons of endothelin receptor antagonists of the second generation in patients with pulmonary hypertension. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(4):72-80 (in Russian)]. DOI:10.26442/terarkh201890472-80
9. Грацианская С.Е., Валиева З.С., Мартынюк Т.В. Достижения современной специфической терапии легочной артериальной и хронической тромбоэмболической легочной гипертензии: фокус на стимулятор растворимой гуанилатциклазы риоцигуат. Терапевтический архив. 2020;92(9):77-84 [Gratsianskaia SE, Valieva ZS, Martynyuk TV, et al. 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. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(9):77-84 (in Russian)]. DOI:10.26442/00403660.2020.09.000717
10. Frantz RP, Schilz RJ, Chakinala MM, et al. Hospitalization and survival in patients using epoprostenol for injection in the PROSPECT observational study. Chest. 2015;147:484-94. DOI:10.1378/chest.14-1004
11. Frost AE, Badesch DB, Miller DP, et al. Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. Chest. 2013;144:1521-9. DOI:10.1378/chest.12-3023
12. 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;50:170740. DOI:10.1183/13993003.00740-2017
13. Diller GP, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: Comparative severity, correlates, and prognostic implication. Circulation. 2005;112:828-35. DOI:10.1161/CIRCULATIONAHA.104.529800
14. Gratsianskaia S, Valieva Z, Taran I, Martynyuk T. The role of the cardiopulmonary exercise testing in assessment of the severity of patients with PAH associated with congenital heart disease. Eur Respir J. 2019;54(Suppl. 63):PA4759
15. Kylhammar D, Kjellström B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-updetermines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39(47):4175-81. DOI:10.1093/eurheartj/ehx257
16. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50:170889. DOI:10.1183/13993003.00889-2017
17. Hoeper MM, Huscher D, Ghofrani HA, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2013;168(2):871-80. DOI:10.1016/j.ijcard.2012.10.026
18. Таран И.Н., Белевская А.А., Валиева З.С., и др. «Портрет» пациентов с идиопатической легочной гипертензией и хронической тромбоэмболической легочной гипертензией в зависимости от коморбидного статуса: особенности течения заболевания и прогноз. Пульмонология. 2020;30(4):427-36 [Taran IN, Belevskaia AA, Valieva ZS, et al. “Portrait” of patients with idiopathic pulmonary hypertension and chronic thromboembolic pulmonary hypertension depending on comorbid status: current and prognosis features. Pul'monologiia. 2020;30(4):427-36 (in Russian)]. DOI:10.18093/0869-0189-2020-30-4-427-436
19. Benza RL, Gomberg-Maitland M, Elliot CG, et al. Predicting survival in patients with pulmonary arterial hypertension: the REVEAL risk score calculator 2.0 and comparison to ESC/ERS-based risk assessment strategies. Chest. 2019;156:323-37. DOI:10.1016/j.chest.2019.02.004
20. Sitbon O, Chin KM, Channick RN, et al. Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study. J Heart Lung Transplant. 2020;39:300-9. DOI:10.1016/j.healun.2019.12.013
21. Galiè N, Barberà JA, Frost AE, et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015;373(9):834-44. DOI:10.1056/NEJMoa1413687
22. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. DOI:10.1183/13993003.01889-2018
23. Hoeper MM, Apitz C, Grünig E, at al. Targeted therapy of pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol. 2018;272S:37-45. DOI:10.1016/j.ijcard.2018.08.082
24. Шмальц А.А., Горбачевский С.В. Возможности и ограничения для начальной комбинированной специфической терапии легочной артериальной гипертензии в Российской Федерации. Терапевтический архив. 2020;92(12):80-5 [Shmalts AA, Gorbachevsky SV. Advantages and limitations of initial combination therapy in pulmonary arterial hypertensionpatients in Russia. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(12):80-5 (in Russian)]. DOI:10.26442/00403660.2020.12.000840
25. Chin KM, Sitbon O, Doelberg M, et al. Efficacy and Safety of Initial Triple Oral Versus Initial Double Oral Combination Therapy in Patients with Newly Diagnosed Pulmonary Arterial Hypertension (PAH): Results of the Randomized Controlled TRITON Study. Am J of Respir and Crit Care Med 2020;201:A2928. Available at: https://www.atsjournals.org/doi/10.1164/ajrccmconference.2020.201.1_MeetingAbstracts.A2928. Accessed: 20.08.2021.
26. Hoeper MM, Corris PA, Kinger JR, et al. The RESPITE Study: Riociguat In Patients With PAH And An Inadequate Response To Phosphodiesterase 5 Inhibitors. Am J Crit Care Med. 2016;193:A6315. DOI:10.1183/13993003.02425-2016
27. 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
28. Hoeper M, Al-Hiti H, Benza RL, et al. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2021:S2213-2600(20)30532-4. DOI:10.1016/S2213-2600(20)30532-4
29. Morrell NW, Aldred MA, Chung WK, et al. Genetics and genomics of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801899. DOI:10.1183/13993003.01899-2018
30. Newman JH. Molecular Rescue in Pulmonary Arterial Hypertension. N Engl J Med. 2021;384(13):1271-2. DOI:10.1056/NEJMe2036314
31. Humbert M, McLaughlin V, Gibbs J, et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med. 2021;384:1204-15. DOI:10.1056/NEJMoa2024277
32. Grimminger F, Schermuly RT. PDGF receptor and its antagonists: role in treatment of PAH. Adv Exp Med Biol. 2010;661:435-46. DOI:10.1007/978-1-60761-500-2_28
33. Shah AM, Campbell P,  Rocha GQ, et al. Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension. Eur Heart J. 2015;36(10):623-32. DOI:10.1093/eurheartj/ehu035
34. Montani D, Bergot E, Günther S, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125:2128 37. DOI:10.1161/CIRCULATIONAHA.111.079921
35. Мартынюк Т.В., Алеевская А.М., Родненков О.В., и др. Ведение пациентов с легочной артериальной гипертензией в условиях пандемии новой коронавирусной инфекции. Евразийский кардиологический журнал. 2020;2:54-60 [Martynyuk TV, Aleevskaya AM, Rodnenkov OV, et al. Management of patients with pulmonary arterial hypertension in the pandemic of a new coronavirus infection. Eurasian Нeart Journal. 2020;2:54-60 (in Russian)]. DOI:10.38109/2225-1685-2020-2-54-60
36. Farha S. COVID-19 and pulmonary hypertension. Cleve Clin J Med. 2020:ccc021. DOI:10.3949/ccjm.87a.ccc021
37. Lee JD, Burger CD, Delossantos GB, et al. A survey-based estimate of COVID-19 Incidence and Outcomes among Patients with PAH or CTEPH and Impact on the Process of Care. Ann Am Thorac Soc. 2020;17(12):1576-82. DOI:10.1513/AnnalsATS.202005-521OC
38. Horn EM, Chakinala M, Oudiz R, et al. Could pulmonary arterial hypertension patients be at a lower risk from severe COVID-19? Pulmonary Circulation. 2020;10(2):1-2. DOI:10.1177/2045894020922799

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1. Chazova IE, Martynyuk TV, Valieva ZS, et al. Eurasian Guidelines for the diagnosis and treatment of pulmonary hypertension. Eurasian Нeart Journal. 2020;1:78-122 (in Russian). DOI:10.38109/2225-1685-2020-1-78-122
2. Galiè 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;37:67-119. DOI:10.1183/13993003.01032-2015
3. D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med. 1991;115:343-9. DOI:10.7326/0003-4819-115-5-343
4. Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142:448-56. DOI:10.1378/chest.11-1460
5. Chazova IE, Arkhipova OA, Valieva ZS, et al. Pulmonary hypertension in Russia: the first results of the National Registry. Terapevticheskii Arkhiv (Ter. Arkh.). 2014;86(9):56-64 (in Russian). DOI:10.26442/00403660.2019.01.000024
6. Chazova I, Martynyuk T, Valieva Z, et al. Clinical and instrumental characteristics of newly diagnosed patients with various forms of pulmonary hypertension according to the Russian National Registry. BioMed Research International. 2020. Article ID 6836973. DOI:10.1155/2020/6836973
7. Martyniuk TV. Pulmonary Hypertension: Diagnosis and Treatment. Series: Library of the Federal State Budgetary Institution “NIMC of Cardiology” of the Ministry of Health of Russia. Moscow: Meditsinskoe informatsionnoe agentstvo. 2018 (in Russian).
8. Martynyuk TV, Nakonechnikov SN, Chazova IE. New horizons of endothelin receptor antagonists of the second generation in patients with pulmonary hypertension. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(4):72-80 (in Russian). DOI:10.26442/terarkh201890472-80
9. Gratsianskaia SE, Valieva ZS, Martynyuk TV, et al. 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. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(9):77-84 (in Russian). DOI:10.26442/00403660.2020.09.000717
10. Frantz RP, Schilz RJ, Chakinala MM, et al. Hospitalization and survival in patients using epoprostenol for injection in the PROSPECT observational study. Chest. 2015;147:484-94. DOI:10.1378/chest.14-1004
11. Frost AE, Badesch DB, Miller DP, et al. Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. Chest. 2013;144:1521-9. DOI:10.1378/chest.12-3023
12. 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;50:170740. DOI:10.1183/13993003.00740-2017
13. Diller GP, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: Comparative severity, correlates, and prognostic implication. Circulation. 2005;112:828-35. DOI:10.1161/CIRCULATIONAHA.104.529800
14. Gratsianskaia S, Valieva Z, Taran I, Martynyuk T. The role of the cardiopulmonary exercise testing in assessment of the severity of patients with PAH associated with congenital heart disease. Eur Respir J. 2019;54(Suppl. 63):PA4759
15. Kylhammar D, Kjellström B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-updetermines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39(47):4175-81. DOI:10.1093/eurheartj/ehx257
16. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50:170889. DOI:10.1183/13993003.00889-2017
17. Hoeper MM, Huscher D, Ghofrani HA, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2013;168(2):871-80. DOI:10.1016/j.ijcard.2012.10.026
18. Taran IN, Belevskaia AA, Valieva ZS, et al. “Portrait” of patients with idiopathic pulmonary hypertension and chronic thromboembolic pulmonary hypertension depending on comorbid status: current and prognosis features. Pul'monologiia. 2020;30(4):427-36 (in Russian). DOI:10.18093/0869-0189-2020-30-4-427-436
19. Benza RL, Gomberg-Maitland M, Elliot CG, et al. Predicting survival in patients with pulmonary arterial hypertension: the REVEAL risk score calculator 2.0 and comparison to ESC/ERS-based risk assessment strategies. Chest. 2019;156:323-37. DOI:10.1016/j.chest.2019.02.004
20. Sitbon O, Chin KM, Channick RN, et al. Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study. J Heart Lung Transplant. 2020;39:300-9. DOI:10.1016/j.healun.2019.12.013
21. Galiè N, Barberà JA, Frost AE, et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015;373(9):834-44. DOI:10.1056/NEJMoa1413687
22. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. DOI:10.1183/13993003.01889-2018
23. Hoeper MM, Apitz C, Grünig E, at al. Targeted therapy of pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol. 2018;272S:37-45. DOI:10.1016/j.ijcard.2018.08.082
24. Shmalts AA, Gorbachevsky SV. Advantages and limitations of initial combination therapy in pulmonary arterial hypertensionpatients in Russia. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(12):80-5 (in Russian). DOI:10.26442/00403660.2020.12.000840
25. Chin KM, Sitbon O, Doelberg M, et al. Efficacy and Safety of Initial Triple Oral Versus Initial Double Oral Combination Therapy in Patients with Newly Diagnosed Pulmonary Arterial Hypertension (PAH): Results of the Randomized Controlled TRITON Study. Am J of Respir and Crit Care Med 2020;201:A2928. Available at: https://www.atsjournals.org/doi/10.1164/ajrccmconference.2020.201.1_MeetingAbstracts.A2928. Accessed: 20.08.2021.
26. Hoeper MM, Corris PA, Kinger JR, et al. The RESPITE Study: Riociguat In Patients With PAH And An Inadequate Response To Phosphodiesterase 5 Inhibitors. Am J Crit Care Med. 2016;193:A6315. DOI:10.1183/13993003.02425-2016
27. 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
28. Hoeper M, Al-Hiti H, Benza RL, et al. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2021:S2213-2600(20)30532-4. DOI:10.1016/S2213-2600(20)30532-4
29. Morrell NW, Aldred MA, Chung WK, et al. Genetics and genomics of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801899. DOI:10.1183/13993003.01899-2018
30. Newman JH. Molecular Rescue in Pulmonary Arterial Hypertension. N Engl J Med. 2021;384(13):1271-2. DOI:10.1056/NEJMe2036314
31. Humbert M, McLaughlin V, Gibbs J, et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med. 2021;384:1204-15. DOI:10.1056/NEJMoa2024277
32. Grimminger F, Schermuly RT. PDGF receptor and its antagonists: role in treatment of PAH. Adv Exp Med Biol. 2010;661:435-46. DOI:10.1007/978-1-60761-500-2_28
33. Shah AM, Campbell P,  Rocha GQ, et al. Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension. Eur Heart J. 2015;36(10):623-32. DOI:10.1093/eurheartj/ehu035
34. Montani D, Bergot E, Günther S, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125:2128 37. DOI:10.1161/CIRCULATIONAHA.111.079921
35. Martynyuk TV, Aleevskaya AM, Rodnenkov OV, et al. Management of patients with pulmonary arterial hypertension in the pandemic of a new coronavirus infection. Eurasian Нeart Journal. 2020;2:54-60 (in Russian). DOI:10.38109/2225-1685-2020-2-54-60
36. Farha S. COVID-19 and pulmonary hypertension. Cleve Clin J Med. 2020:ccc021. DOI:10.3949/ccjm.87a.ccc021
37. Lee JD, Burger CD, Delossantos GB, et al. A survey-based estimate of COVID-19 Incidence and Outcomes among Patients with PAH or CTEPH and Impact on the Process of Care. Ann Am Thorac Soc. 2020;17(12):1576-82. DOI:10.1513/AnnalsATS.202005-521OC
38. Horn EM, Chakinala M, Oudiz R, et al. Could pulmonary arterial hypertension patients be at a lower risk from severe COVID-19? Pulmonary Circulation. 2020;10(2):1-2. DOI:10.1177/2045894020922799

Т.В. Мартынюк*, И.Е. Чазова1

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
*trukhiniv@mail.ru

________________________________________________

Tamila V. Martynyuk*1,2, Irina E. Chazova1

1 Myasnikov Institute of Clinical Cardiology, National Medical Research Center of Cardiology, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia
*trukhiniv@mail.ru