Проблемные аспекты легочной гипертензии вследствие патологии левых отделов сердца: фокус на комбинированную пост/прекапиллярную форму

1. Мартынюк Т.В. Легочная гипертензия: диагностика и лечение. М.: Медицинское информационное агентство, 2018 [Martynyuk T.V. Pulmonary hypertension: diagnosis and treatment. Moscow: Medical news Agency, 2018 (In Russ.)]. 
2. Vachiéry J-L, Tedford RJ, Rosenkranz S, et al. Pulmonary hypertension due to left heart disease. Eur Respir J. 2019;53:1801-97. doi: 10.1183/13993003.01897-2018 
3. Vachiéry JL, Adir Y, Barberà JA, et al. Pulmonary Hypertension Due to Left Heart Diseases. J Am Coll Cardiol. 2013;62:100-8. doi: 10.1016/j.jacc.2013.10.033  
4. 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
5. 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 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
6. Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(Suppl. 25):42-50. doi: 10.1016/j.jacc.2013.10.032
7. Wood P. Pulmonary hypertension with special reference to the vasoconstrictive factor.  Brit Heart J. 1958;20(4):557-70. doi: 10.1136/hrt.20.4.557
8. Assad TR, Hemnes AR, Larkin EK, et al. Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension. J Am Coll Cardiol. 2016;68(23):2525-36. doi: 10.1016/j.jacc.2016.09.942
9. Porter TR, Taylor DO, Cycan A, et al. Endothelium-dependent pulmonary artery responses in chronic heart failure: influence of pulmonary hypertension. J Am Coll Cardiol. 1993;22:1418-24. 
10. Moraes DL, Colucci WS, Givertz MM. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000;102:1718-23. doi: 10.1161/01.cir.102.14.1718
11. Givertz MM, Colucci WS, LeJemtel TH, et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation. 2000;101:2922-7. doi: 10.1161/01.CIR.101.25.2922
12. Spieker LE, Mitrovic V, Noll G, et al. Acute hemodynamic and neurohumoral effects of selective ETA receptor blockade in patients with congestive heart failure. J Am Coll Cardiol. 2000;101:2945-52. doi: 10.1016/s0735-1097(00)00649-5
13. Rosenkranz S, Gibbs JS, Wachter R, et al. Left ventricular heart failure and pulmonary hypertension. Eur Heatr J. 2016;37:942-54. doi: 10.1093/eurheartj/ehv512
14. Butler J, Stankewicz MA, Wu J, et al. Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation. J Heart Lung Transplant. 2005;24:170-7. doi: 10.1016/j.healun.2003.09.045
15. Frost AE, Farber HW, Barst RJ, et al. Demographics and outcomes of patients diagnosed with pulmonary hypertension with pulmonary capillary wedge pressures 16 to 18 mm Hg: Insights from the REVEAL registry. Chest. 2013;143(1):185-95. doi: 10.1378/chest.11-1387 doi: 10.1378/chest.11-1387 
16. Caravita S, Faini A, Carolino D'Araujo S, et al. Clinical phenotypes and outcomes of pulmonary hypertension due to left heart disease: Role of the pre-capillary component. PLoS One. 2018;13(6):e0199164. doi: 10.1371/journal.pone.0199164 
17. Tampakakis E, Leary PJ, Selby VN, et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart Fail. 2014;3(1):9-16. doi: 10.1016/j.jchf.2014.07.010
18. Dalen JE, Dexter L, Ockene IS, Carlson J. Precapillary pulmonary hypertension; its relationship to pulmonary venous hypertension. Trans Am Clin Climatol Assoc. 1975;86:207. 
19. 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; 53(17): 573-619.  doi: 10.1016/j.jacc.2009.01.004
20. Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012;126:975-90. doi: 10.1161/CIRCULATIONAHA.111.085761
21. Stevens PM. Assessment of acute respiratory failure: cardiac versus pulmonary causes. Chest. 1975;67:1-2. doi: 10.1378/chest.67.1.1
22. Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J. 2013;41:217-23. doi: 10.1183/09031936.00074312
23. Gerges G, Gerges M, Lang MB, et al. Diastolic Pulmonary Vascular Pressure Gradient: A Predictor of Prognosis in "Out-of-Proportion" Pulmonary Hypertension. Chest. 2013;143(3):758-66. doi: 10.1378/chest.12-1653
24. Palazzini M, Dardi F, Manes A, et al. Pulmonary hypertension due to left heart disease: analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS guidelines and insights for future changes. Eur J Heart Fail. 2018;20:248-55. doi: 10.1002/ejhf.860
25. Fujimoto N, Borlaug BA, Lewis GD, et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation. 2013;127:55-62. doi: 10.1161/CIRCULATIONAHA.112.111302
26. Мартынюк Т.В. Общие принципы диагностики. Глава в монографии «Легочная гипертензия». Под ред. И.Е. Чазовой, Т.В. Мартынюк. М.: Практика, 2015; с. 103-55. [Martynyuk TV. General principles of diagnostics. Chapter in the monograph “Pulmonary hypertension”. In: Chazova IE, Martynyuk TV. M.: Praktika, 2015: p. 103-55 (In Russ.)]. 
27. Мартынюк Т.В. Легочная гипертензия при заболеваниях левых отделов сердца. Глава в монографии «Легочная гипертензия». Под ред. С.Н. Авдеева. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2019; с. 290-319. [Martynyuk TV. Pulmonary hypertension in diseases of the left heart. Chapter in the monograph “Pulmonary hypertension”. 
In: SN. Avdeev. M.: GEOTAR-Media, 2019: p. 290-319 (In Russ.)]. 
28. Kovacs G, Dumitrescu D, Barner A, et al. Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol. 2018;272S:11-9. doi: 10.1016/j.ijcard.2018.08.083
29. Vahanian A, Baumgartner H, Bax J, et al. Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology; ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007;28:230-68. doi: 10.1093/eurheartj/ehl428
30. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787-847. doi: 10.1093/eurheartj/ehs104
31. Федеральные клинические рекомендации по диагностике и лечению хронической и острой сердечной недостаточности [Federal Clinical Guidelines on diagnosis and treatment of chronic and acute heart failure (In Russ.)]. http://doctor-ru.org
32. Abraham WT, Adamson PB, Bourge RC, et al; for the CHAMPION Trial Study Group. Wireless pulmonary artery hemodynamic monitoring in chronic heart failure: A randomized controlled trial. Lancet. 2011;377:658-66. doi: 10.1016/S0140-6736(11)60101-3
33. Adamson PB, Abraham WT, Bourge RC, et al. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail. 2014;7:935-44. doi: 10.1161/CIRCHEARTFAILURE.113.001229
34. Katz SD, Balidemaj K, Homma S, et al. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilatation in patients with chronic heart failure. J Am Coll Cardiol. 2000;36:845-51. doi: 10.1016/S0735-1097(00)00790-7
35. Packer М, John JVM, Krum H, et al. Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the ENABLE Trials. JACC: Heart Failure. 2017;5(Issue 5):317-26. doi: 10.1016/j.jchf.2017.02.021
36. Kalra P, Moons JC, Coats AJ. Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure? Int J Cardiol. 2002;85:195-7. doi: 10.1016/s0167-5273(02)00182-1
37. Anand I, McMurray J, Cohn JN, et al. EARTH investigators. Long-term effects of darusentan on left-ventricular remodeling and clinical outcomes in the Endotelin A Receptor Antagonist Trial in Heart Failure (EARTH): randomized, double-blind, placebo-controlled trial. Lancet. 2004;364:347-54. doi: 10.1016/S0140-6736(04)16723-8
38. Lüscher TF, Enseleit F, Pacher R, et al. Heart Failure ET(A) Receptor Blockade Trial. Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT). Circulation. 2002;106:2666-72. doi: 10.1161/01.cir.0000038497.80095.e1  
39. Califf RM, Adams KF, McKenna WJ, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134:44-54.
40. Barnett CF, De Marco T. Pulmonary hypertension associated with left-side heart disease. Heart Fail Clin. 2012;8:447-59. doi: 10.1016/s0002-8703(97)70105-4
41. Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007;116:1555-62. doi: 10.1161/CIRCULATIONAHA.107.716373
42. Bocchi EA, Guimarães G, Mocelin A, et al. Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction. Circulation. 2002;106:1097-103. doi: 10.1161/01.cir.0000027149.83473.b6
43. Guazzi M, Samaja M, Arena R, et al. Long-term use of sildenafil in the therapeutic management of heart failure. J Am Coll Cardiol. 2007;50:2136-44. doi: 10.1016/j.jacc.2007.07.078
44. Bermejo J, Yotti R, García-Orta R, et al. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J. 2018;39:1255-64. doi: 10.1093/eurheartj/ehx700
45. Bonderman D, Ghio S, Felix SB, et al. Riociguat for patients with pulmonary hypertension due to systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo controlled, dose-ranging hemodynamic study. Circulation. 2013;128:502-11. doi: 10.1161/CIRCULATIONAHA.113.001458
46. Bonderman D, Pretsch I, Steringer-Mascherbauer R, et al. Acute hemodynamic effects of riociguat in patients wi.th pulmonary hypertension associated with diastolic heart failure (DILATE-1): a randomized, double-blind, placebo-controlled, single-dose study. Chest. 2014; 146:1274-85. doi: 10.1378/chest.14-0106
47. Vachiéry JL, Delcroix M, Al-Hilty H, et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J. 2018;51:1702589. doi: 10.1183/13993003.01886-2017
48. ClinicalTrials.gov. A Multi-center, Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of Macitentan in Subjects With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease (SERENADE). https://clinicaltrials.gov/ct2/show/ NCT03153111. Date last updated: July, 2018. 
49. ClinicalTrials.gov. A Prospective, Multicenter, Double blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of Macitentan in Patients With Pulmonary Hypertension After Left Ventricular Assist Device Implantation (SOPRANO). https://clinicaltrials.gov/ct2/show/NCT02554903. Date last verified: February, 2018.
50. Karoor V, Oka M, Walchak SJ, et al. Neprilysin regulates pulmonary artery smooth muscle cell phenotype through a platelet-derived growth factor receptor-dependent mechanism. Hypertension. 2013;61(4):921-30. doi: 10.1161/HYPERTENSIONAHA.111.199588
51. Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan) (PARENT). NCT02788656. https://clinicaltrials.gov/ct2/show/
record/NCT02788656

________________________________________________

1. Martynyuk T.V. Pulmonary hypertension: diagnosis and treatment. Moscow: Medical news Agency, 2018 (In Russ.)
2. Vachiéry J-L, Tedford RJ, Rosenkranz S, et al. Pulmonary hypertension due to left heart disease. Eur Respir J. 2019;53:1801-97. doi: 10.1183/13993003.01897-2018 
3. Vachiéry JL, Adir Y, Barberà JA, et al. Pulmonary Hypertension Due to Left Heart Diseases. J Am Coll Cardiol. 2013;62:100-8. doi: 10.1016/j.jacc.2013.10.033  
4. 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
5. Chazova IE, Martynyuk TV, Valieva ZS, et al. 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
6. Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(Suppl. 25):42-50. doi: 10.1016/j.jacc.2013.10.032
7. Wood P. Pulmonary hypertension with special reference to the vasoconstrictive factor.  Brit Heart J. 1958;20(4):557-70. doi: 10.1136/hrt.20.4.557
8. Assad TR, Hemnes AR, Larkin EK, et al. Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension. J Am Coll Cardiol. 2016;68(23):2525-36. doi: 10.1016/j.jacc.2016.09.942
9. Porter TR, Taylor DO, Cycan A, et al. Endothelium-dependent pulmonary artery responses in chronic heart failure: influence of pulmonary hypertension. J Am Coll Cardiol. 1993;22:1418-24. 
10. Moraes DL, Colucci WS, Givertz MM. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000;102:1718-23. doi: 10.1161/01.cir.102.14.1718
11. Givertz MM, Colucci WS, LeJemtel TH, et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation. 2000;101:2922-7. doi: 10.1161/01.CIR.101.25.2922
12. Spieker LE, Mitrovic V, Noll G, et al. Acute hemodynamic and neurohumoral effects of selective ETA receptor blockade in patients with congestive heart failure. J Am Coll Cardiol. 2000;101:2945-52. doi: 10.1016/s0735-1097(00)00649-5
13. Rosenkranz S, Gibbs JS, Wachter R, et al. Left ventricular heart failure and pulmonary hypertension. Eur Heatr J. 2016;37:942-54. doi: 10.1093/eurheartj/ehv512
14. Butler J, Stankewicz MA, Wu J, et al. Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation. J Heart Lung Transplant. 2005;24:170-7. doi: 10.1016/j.healun.2003.09.045
15. Frost AE, Farber HW, Barst RJ, et al. Demographics and outcomes of patients diagnosed with pulmonary hypertension with pulmonary capillary wedge pressures 16 to 18 mm Hg: Insights from the REVEAL registry. Chest. 2013;143(1):185-95. doi: 10.1378/chest.11-1387 doi: 10.1378/chest.11-1387 
16. Caravita S, Faini A, Carolino D'Araujo S, et al. Clinical phenotypes and outcomes of pulmonary hypertension due to left heart disease: Role of the pre-capillary component. PLoS One. 2018;13(6):e0199164. doi: 10.1371/journal.pone.0199164 
17. Tampakakis E, Leary PJ, Selby VN, et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart Fail. 2014;3(1):9-16. doi: 10.1016/j.jchf.2014.07.010
18. Dalen JE, Dexter L, Ockene IS, Carlson J. Precapillary pulmonary hypertension; its relationship to pulmonary venous hypertension. Trans Am Clin Climatol Assoc. 1975;86:207. 
19. 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; 53(17): 573-619.  doi: 10.1016/j.jacc.2009.01.004
20. Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012;126:975-90. doi: 10.1161/CIRCULATIONAHA.111.085761
21. Stevens PM. Assessment of acute respiratory failure: cardiac versus pulmonary causes. Chest. 1975;67:1-2. doi: 10.1378/chest.67.1.1
22. Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J. 2013;41:217-23. doi: 10.1183/09031936.00074312
23. Gerges G, Gerges M, Lang MB, et al. Diastolic Pulmonary Vascular Pressure Gradient: A Predictor of Prognosis in "Out-of-Proportion" Pulmonary Hypertension. Chest. 2013;143(3):758-66. doi: 10.1378/chest.12-1653
24. Palazzini M, Dardi F, Manes A, et al. Pulmonary hypertension due to left heart disease: analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS guidelines and insights for future changes. Eur J Heart Fail. 2018;20:248-55. doi: 10.1002/ejhf.860
25. Fujimoto N, Borlaug BA, Lewis GD, et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation. 2013;127:55-62. doi: 10.1161/CIRCULATIONAHA.112.111302
26. Martynyuk TV. General principles of diagnostics. Chapter in the monograph “Pulmonary hypertension”. In: Chazova IE, Martynyuk TV. M.: Praktika, 2015: p. 103-55 (In Russ.)
27. Martynyuk TV. Pulmonary hypertension in diseases of the left heart. Chapter in the monograph “Pulmonary hypertension”. In: SN. Avdeev. M.: GEOTAR-Media, 2019: p. 290-319 (In Russ.) 
28. Kovacs G, Dumitrescu D, Barner A, et al. Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol. 2018;272S:11-9. doi: 10.1016/j.ijcard.2018.08.083
29. Vahanian A, Baumgartner H, Bax J, et al. Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology; ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007;28:230-68. doi: 10.1093/eurheartj/ehl428
30. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787-847. doi: 10.1093/eurheartj/ehs104
31. Federal Clinical Guidelines on diagnosis and treatment of chronic and acute heart failure (In Russ.) http://doctor-ru.org
32. Abraham WT, Adamson PB, Bourge RC, et al; for the CHAMPION Trial Study Group. Wireless pulmonary artery hemodynamic monitoring in chronic heart failure: A randomized controlled trial. Lancet. 2011;377:658-66. doi: 10.1016/S0140-6736(11)60101-3
33. Adamson PB, Abraham WT, Bourge RC, et al. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail. 2014;7:935-44. doi: 10.1161/CIRCHEARTFAILURE.113.001229
34. Katz SD, Balidemaj K, Homma S, et al. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilatation in patients with chronic heart failure. J Am Coll Cardiol. 2000;36:845-51. doi: 10.1016/S0735-1097(00)00790-7
35. Packer М, John JVM, Krum H, et al. Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the ENABLE Trials. JACC: Heart Failure. 2017;5(Issue 5):317-26. doi: 10.1016/j.jchf.2017.02.021
36. Kalra P, Moons JC, Coats AJ. Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure? Int J Cardiol. 2002;85:195-7. doi: 10.1016/s0167-5273(02)00182-1
37. Anand I, McMurray J, Cohn JN, et al. EARTH investigators. Long-term effects of darusentan on left-ventricular remodeling and clinical outcomes in the Endotelin A Receptor Antagonist Trial in Heart Failure (EARTH): randomized, double-blind, placebo-controlled trial. Lancet. 2004;364:347-54. doi: 10.1016/S0140-6736(04)16723-8
38. Lüscher TF, Enseleit F, Pacher R, et al. Heart Failure ET(A) Receptor Blockade Trial. Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT). Circulation. 2002;106:2666-72. doi: 10.1161/01.cir.0000038497.80095.e1  
39. Califf RM, Adams KF, McKenna WJ, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134:44-54.
40. Barnett CF, De Marco T. Pulmonary hypertension associated with left-side heart disease. Heart Fail Clin. 2012;8:447-59. doi: 10.1016/s0002-8703(97)70105-4
41. Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007;116:1555-62. doi: 10.1161/CIRCULATIONAHA.107.716373
42. Bocchi EA, Guimarães G, Mocelin A, et al. Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction. Circulation. 2002;106:1097-103. doi: 10.1161/01.cir.0000027149.83473.b6
43. Guazzi M, Samaja M, Arena R, et al. Long-term use of sildenafil in the therapeutic management of heart failure. J Am Coll Cardiol. 2007;50:2136-44. doi: 10.1016/j.jacc.2007.07.078
44. Bermejo J, Yotti R, García-Orta R, et al. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J. 2018;39:1255-64. doi: 10.1093/eurheartj/ehx700
45. Bonderman D, Ghio S, Felix SB, et al. Riociguat for patients with pulmonary hypertension due to systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo controlled, dose-ranging hemodynamic study. Circulation. 2013;128:502-11. doi: 10.1161/CIRCULATIONAHA.113.001458
46. Bonderman D, Pretsch I, Steringer-Mascherbauer R, et al. Acute hemodynamic effects of riociguat in patients wi.th pulmonary hypertension associated with diastolic heart failure (DILATE-1): a randomized, double-blind, placebo-controlled, single-dose study. Chest. 2014; 146:1274-85. doi: 10.1378/chest.14-0106
47. Vachiéry JL, Delcroix M, Al-Hilty H, et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J. 2018;51:1702589. doi: 10.1183/13993003.01886-2017
48. ClinicalTrials.gov. A Multi-center, Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of Macitentan in Subjects With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease (SERENADE). https://clinicaltrials.gov/ct2/show/ NCT03153111. Date last updated: July, 2018. 
49. ClinicalTrials.gov. A Prospective, Multicenter, Double blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of Macitentan in Patients With Pulmonary Hypertension After Left Ventricular Assist Device Implantation (SOPRANO). https://clinicaltrials.gov/ct2/show/NCT02554903. Date last verified: February, 2018.
50. Karoor V, Oka M, Walchak SJ, et al. Neprilysin regulates pulmonary artery smooth muscle cell phenotype through a platelet-derived growth factor receptor-dependent mechanism. Hypertension. 2013;61(4):921-30. doi: 10.1161/HYPERTENSIONAHA.111.199588
51. Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan) (PARENT). NCT02788656. https://clinicaltrials.gov/ct2/show/
record/NCT02788656

А.М. Алеевская1, О.Н. Выборов1, В.В. Грамович1, Т.В. Мартынюк1,2

1 ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия

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A.M. Aleevskaya1, O.N. Vyborov1, V.V. Gramovich1, T.V. Martynyuk1,2

1 National Medical Research Center for Cardiology, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia