2. Galie N., McLaughlin V.V., Rubin L.J. et al. An overview of the 6th World Symposium on Pulmonary Hypertension. Eur Respir J. 2019; 53(1): 1802148. https://dx.doi.org/10.1183/13993003.02148-2018.

3. Humbert M., Kovacs G., Hoeper M.M. et al.; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022; 43(38): 3618–31. https://dx.doi.org/10.1093/eurheartj/ehac237.

4. Lau E.M.T., Giannoulatou E., Celermajer D.S. et al. Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol. 2017; 14(10): 603–14. https://dx.doi.org/10.1038/nrcardio.2017.84.

5. Leber L., Beaudet A., Muller A. Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Identification of the most accurate estimates from a systematic literature review. Pulm Circ. 2021; 11(1): 2045894020977300. https://dx.doi.org/10.1177/2045894020977300.

6. O’Callaghan D.S., Savale L., Montani D. et al. Treatment of pulmonary arterial hypertension with targeted therapies. Nat Rev Cardiol. 2011; 8(9): 526–38. https://dx.doi.org/10.1038/nrcardio.2011.104.

7. Barst R.J., Chung L., Zamanian R.T. et al. Functional class improvement and 3-year survival outcomes in patients with pulmonary arterial hypertension in the REVEAL Registry. Chest. 2013; 144(1): 160–68. https://dx.doi.org/10.1378/chest.12-2417.

8. Galie N., Humbert M., Vachiery J.L. et al.; ESC Scientific Document Group. 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. https://dx.doi.org/10.1093/eurheartj/ehv317.

9. Hoeper M.M., 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(2): 1700740. https://dx.doi.org/10.1183/13993003.00740-2017.

10. Badagliacca R., Papa S., Manzi G. et al. Usefulness of adding echocardiography of the right heart to risk-assessment scores in prostanoid-treated pulmonary arterial hypertension. JACC Cardiovasc Imaging. 2020; 13(9): 2054–56.https://dx.doi.org/10.1016/j.jcmg.2020.04.005.

11. Lewis R.A., Johns C.S., Cogliano M. et al. Identification of cardiac magnetic resonance imaging thresholds for risk stratification in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2020; 201(4): 458–68. https://dx.doi.org/10.1164/rccm.201909-1771OC.

12. Weatherald J., Boucly A., Chemla D. et al. Prognostic value of follow-up hemodynamic variables after initial management in pulmonary arterial hypertension. Circulation. 2018; 137(7): 693–704. https://dx.doi.org/10.1161/CIRCULATIONAHA.117.029254.

13. Savarese G., Paolillo S., Costanzo P. et al. Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials. J Am Coll Cardiol. 2012; 60(13): 1192–201.https://dx.doi.org/10.1016/j.jacc.2012.01.083

14. Warwick G., Thomas P.S., Yates D.H. Biomarkers in pulmonary hypertension. Eur Respir J. 2008; 32(2): 503–12.https://dx.doi.org/10.1183/09031936.00160307.

15. Hoeper M.M., 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(2): 1700740.https://dx.doi.org/10.1183/13993003.00740-2017.

16. Hoeper M.M., Pausch C., Olsson K.M. et al. COMPERA 2.0: A refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. 2022; 60(1): 2102311. https://dx.doi.org/10.1183/13993003.02311-2021.

17. Rich S., Kaufmann E., Levy P.S. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med. 1992; 327(2): 76–81. https://dx.doi.org/10.1056/NEJM199207093270203.

18. McKeever R.G., Hamilton R.J. Calcium channel blockers. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.

19. Sitbon O., Humbert M., Jais X. et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005; 111(23): 3105–11. https://dx.doi.org/10.1161/CIRCULATIONAHA.104.488486.

20. Galie N., Ussia G., Passarelli P. et al. Role of pharmacologic tests in the treatment of primary pulmonary hypertension. Am J Cardiol. 1995; 75(3): 55A–62A. https://dx.doi.org/10.1016/s0002-9149(99)80384-1.

21. Correale M., Ferraretti A., Monaco I. et al. Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: Where do we stand? Vasc Health Risk Manag. 2018; 14: 253–64. https://dx.doi.org/10.2147/VHRM.S133921.

22. Denton C.P., Humbert M., Rubin L. et al. Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Ann Rheum Dis. 2006; 65(10): 1336–40.https://dx.doi.org/10.1136/ard.2005.048967.

23. Humbert M., Barst R.J., Robbins I.M. et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004; 24(3): 353–59. https://dx.doi.org/10.1183/09031936.04.00028404.

24. Gatzoulis M.A., Beghetti M., Galie N. et al.; BREATHE-5 Investigators. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: Results of the BREATHE-5 open-label extension study. Int J Cardiol. 2008; 127(1): 27–32.https://dx.doi.org/10.1016/j.ijcard.2007.04.078.

25. Simonneau G., Galie N., Jansa P. et al. Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients. Int J Cardiol. 2014; 172(2): 332–39. https://dx.doi.org/10.1016/j.ijcard.2013.12.179.

26. McLaughlin V., Channick R.N., Ghofrani H.A. et al. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. 2015; 46(2): 405–13. https://dx.doi.org/10.1183/13993003.02044-2014.

27. Rubin L.J., Badesch D.B., Barst R.J. et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002; 346(12): 896–903. https://dx.doi.org/10.1056/NEJMoa012212. Erratum in: N Engl J Med. 2002; 346(16): 1258.

28. Galie N., Olschewski H., Oudiz R.J. et al; Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies (ARIES) Group. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008; 117(23): 3010–19. https://dx.doi.org/10.1161/CIRCULATIONAHA.107.742510.

29. Simonneau G., Channick R.N., Delcroix M. et al. Incident and prevalent cohorts with pulmonary arterial hypertension: Insight from SERAPHIN. Eur Respir J. 2015; 46(6): 1711–20. https://dx.doi.org/10.1183/13993003.00364-2015.

30. McLaughlin V., Hoeper M., Tamura Y. et al. UNISUS study design: a phase 3 superiority study comparing the efficacy, safety, and tolerability of macitentan 75 mg vs macitentan 10 mg in patients with pulmonary arterial hypertension (PAH). Eur Heart J. 2022; 43(2): ehac544.1929. https://dx.doi.org/10.1093/eurheartj/ehac544.1929.

31. Humbert M., Segal E.S., Kiely D.G. et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J. 2007; 30(2): 338–44. https://dx.doi.org/10.1183/09031936.00138706.

32. Clozel M., Maresta A., Humbert M. Endothelin receptor antagonists. Handb Exp Pharmacol. 2013; 218: 199–227.https://dx.doi.org/10.1007/978-3-642-38664-0_9.

33. Vachiery J.L., Galie N., Barbera J.A. et al.; AMBITION Study Group. Initial combination therapy with ambrisentan + tadalafil on pulmonary arterial hypertension-related hospitalization in the AMBITION trial. J Heart Lung Transplant. 2019; 38(2): 194–202.https://dx.doi.org/10.1016/j.healun.2018.11.006.

34. Galie N., Brundage B.H., Ghofrani H.A. et al.; Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009; 119(22): 2894–903.https://dx.doi.org/10.1161/CIRCULATIONAHA.108.839274. Erratum in: Circulation. 2011; 124(10): e279.

35. Padda I.S., Tripp J. Phosphodiesterase Inhibitors. [Updated 2022 Nov 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.

36. Galie N., Ghofrani H.A., Torbicki A. et al.; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005; 353(20): 2148–57.https://dx.doi.org/10.1056/NEJMoa050010. Erratum in: N Engl J Med. 2006; 354(22): 2400–1.

37. Rubin L.J., Badesch D.B., Fleming T.R. et al.; SUPER-2 Study Group. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: The SUPER-2 study. Chest. 2011; 140(5): 1274–83. https://dx.doi.org/10.1378/chest.10-0969.

38. Ghofrani H.A., Galie N., Grimminger F. et al.; PATENT-1 Study Group. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013; 369(4): 330–40. https://dx.doi.org/10.1056/NEJMoa1209655.

39. Rubin L.J., Galie N., Grimminger F. et al. Riociguat for the treatment of pulmonary arterial hypertension: A long-term extension study (PATENT-2). Eur Respir J. 2015; 45(5): 1303–13. https://dx.doi.org/10.1183/09031936.00090614.

40. Hoeper M.M., Simonneau G., Corris P.A. 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. https://dx.doi.org/10.1183/13993003.02425-2016.

41. Hoeper M.M., Al-Hiti H., Benza R.L. et al.; REPLACE investigators. 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; 9(6): 573–84. https://dx.doi.org/10.1016/S2213-2600(20)30532-4.

42. Galie N., Manes A., Branzi A. Prostanoids for pulmonary arterial hypertension. Am J Respir Med. 2003; 2(2): 123–37.https://dx.doi.org/10.1007/BF03256644.

43. Clapp L.H., Abu-Hanna J.H.J., Patel J.A. Diverse pharmacology of prostacyclin mimetics: Implications for pulmonary hypertension. In: Nakanishi, T., Baldwin, H., Fineman, J., Yamagishi, H. (eds) Molecular mechanism of congenital heart disease and pulmonary hypertension. Springer, Singapore. https://doi.org/10.1007/978-981-15-1185-1_5.

44. Olschewski H. Inhaled iloprost for the treatment of pulmonary hypertension. Eur Respir Rev. 2009; 18(111): 29–34.https://dx.doi.org/10.1183/09059180.00011111.

45. Hoeper M.M., Leuchte H., Halank M. et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2006; 28(4): 691–94. https://dx.doi.org/10.1183/09031936.06.00057906.

46. McLaughlin V.V., Oudiz R.J., Frost A. et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006; 174(11): 1257–63. https://dx.doi.org/10.1164/rccm.200603-358OC.

47. Kuwano K., Hashino A., Noda K. et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), ameliorates rat pulmonary hypertension with unique relaxant responses of its active form, {4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (MRE-269), on rat pulmonary artery. J Pharmacol Exp Ther. 2008; 326(3): 691–99. https://dx.doi.org/10.1124/jpet.108.138305.

48. Sitbon O., Channick R., Chin K.M. et al.; GRIPHON Investigators. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015; 373(26): 2522–33. https://dx.doi.org/10.1056/NEJMoa1503184.

49. Chin K., Sitbon O., Doelberg M. et al. Three- versus two-drug therapy for patients with newly diagnosed pulmonary arterial hypertension. J Am Coll Cardiol. 2021; 78(14): 1393–403. https://dx.doi.org/10.1016/j.jacc.2021.07.057.