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Current Treatment Strategies, Guidelines and New Therapies

  • Chapter
Treatment of Pulmonary Hypertension

Part of the book series: Current Cardiovascular Therapy ((CCT))

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Abstract

Historically, primary pulmonary hypertension (as it was then termed) has been considered a rapidly progressive, fatal condition with no effective therapies with an average life expectancy of less than 3 years at diagnosis [1]. It has been labelled as a “desperate disease” and upon diagnosis one enters “the kingdom of the near-dead” [2].

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References

  1. D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343–9.

    PubMed  Google Scholar 

  2. Robin ED. The kingdom of the near-dead. The shortened unnatural life history of primary pulmonary hypertension. Chest. 1987;92(2):330–4.

    CAS  PubMed  Google Scholar 

  3. Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med. 1992;327(2):76–81.

    CAS  PubMed  Google Scholar 

  4. NHS Commissioning Board. Commissioning Policy Statement: National policy for targeted therapies for the treatment of pulmonary hypertension in adults. March 2013. Available from: http://www.england.nhs.uk/wp-content/uploads/2013/04/a11-ps-a.pdf.

  5. Galie N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394–403.

    PubMed Central  PubMed  Google Scholar 

  6. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448–56.

    PubMed  Google Scholar 

  7. Barst RJ, Langleben D, Badesch D, Frost A, Lawrence EC, Shapiro S, et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol. 2006;47(10):2049–56.

    CAS  PubMed  Google Scholar 

  8. Lavelle A, Sugrue R, Lawler G, Mulligan N, Kelleher B, Murphy DM, et al. Sitaxentan-induced hepatic failure in two patients with pulmonary arterial hypertension. Eur Respir J. 2009;34(3):770–1.

    CAS  PubMed  Google Scholar 

  9. Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013;158(9):641–9.

    PubMed  Google Scholar 

  10. Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903.

    CAS  PubMed  Google Scholar 

  11. Galie N, Rubin L, Hoeper M, Jansa P, Al-Hiti H, Meyer G, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371(9630):2093–100.

    CAS  PubMed  Google Scholar 

  12. Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, et al. 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):3010–9.

    CAS  PubMed  Google Scholar 

  13. Oudiz RJ, Galie N, Olschewski H, Torres F, Frost A, Ghofrani HA, et al. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(21):1971–81.

    PubMed  Google Scholar 

  14. Badesch DB, Feldman J, Keogh A, Mathier MA, Oudiz RJ, Shapiro S, et al. ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension. Cardiovasc Ther. 2012;30(2):93–9.

    CAS  PubMed  Google Scholar 

  15. Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–18.

    CAS  PubMed  Google Scholar 

  16. Prasad S, Wilkinson J, Gatzoulis MA. Sildenafil in primary pulmonary hypertension. N Engl J Med. 2000;343(18):1342.

    CAS  PubMed  Google Scholar 

  17. Wilkens H, Guth A, Konig J, Forestier N, Cremers B, Hennen B, et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001;104(11):1218–22.

    CAS  PubMed  Google Scholar 

  18. Lepore JJ, Maroo A, Pereira NL, Ginns LC, Dec GW, Zapol WM, et al. Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol. 2002;90(6):677–80.

    CAS  PubMed  Google Scholar 

  19. Madden BP, Sheth A, Wilde M, Ong YE. Does Sildenafil produce a sustained benefit in patients with pulmonary hypertension associated with parenchymal lung and cardiac disease? Vascul Pharmacol. 2007;47(2–3):184–8.

    CAS  PubMed  Google Scholar 

  20. Sastry BK, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol. 2004;43(7):1149–53.

    CAS  PubMed  Google Scholar 

  21. Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–57.

    CAS  PubMed  Google Scholar 

  22. Pepke-Zaba J, Gilbert C, Collings L, Brown MC. Sildenafil improves health-related quality of life in patients with pulmonary arterial hypertension. Chest. 2008;133(1):183–9.

    CAS  PubMed  Google Scholar 

  23. Rubin LJ, Badesch DB, Fleming TR, Galie N, Simonneau G, Ghofrani HA, et al. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study. Chest. 2011;140(5):1274–83.

    CAS  PubMed  Google Scholar 

  24. Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894–903.

    CAS  PubMed  Google Scholar 

  25. Jing ZC, Yu ZX, Shen JY, Wu BX, Xu KF, Zhu XY, et al. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2011;183(12):1723–9.

    CAS  PubMed  Google Scholar 

  26. Rubin LJ, Mendoza J, Hood M, McGoon M, Barst R, Williams WB, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med. 1990;112(7):485–91.

    CAS  PubMed  Google Scholar 

  27. Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med. 1994;121(6):409–15.

    CAS  PubMed  Google Scholar 

  28. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296–301.

    CAS  PubMed  Google Scholar 

  29. Higenbottam T, Butt AY, McMahon A, Westerbeck R, Sharples L. Long-term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension. Heart (British Cardiac Society). 1998;80(2):151–5.

    CAS  Google Scholar 

  30. Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165(6):800–4.

    PubMed  Google Scholar 

  31. Tapson VF, Jing ZC, Xu KF, Pan L, Feldman J, Kiely DG, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2013;144(3):952–8.

    CAS  PubMed  Google Scholar 

  32. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347(5):322–9.

    CAS  PubMed  Google Scholar 

  33. Galie N, Humbert M, Vachiery JL, Vizza CD, Kneussl M, Manes A, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2002;39(9):1496–502.

    CAS  PubMed  Google Scholar 

  34. Barst RJ, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2003;41(12):2119–25.

    CAS  PubMed  Google Scholar 

  35. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Kreckel A, et al. Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol. 2003;42(1):158–64.

    CAS  PubMed  Google Scholar 

  36. Hoeper MM, Taha N, Bekjarova A, Gatzke R, Spiekerkoetter E. Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Eur Respir J. 2003;22(2):330–4.

    CAS  PubMed  Google Scholar 

  37. Hoeper MM, Leuchte H, Halank M, Wilkens H, Meyer FJ, Seyfarth HJ, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2006;28(4):691–4.

    CAS  PubMed  Google Scholar 

  38. McLaughlin VV, Oudiz RJ, Frost A, Tapson VF, Murali S, Channick RN, 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.

    CAS  PubMed  Google Scholar 

  39. Humbert M, Barst RJ, Robbins IM, Channick RN, Galie N, Boonstra A, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004;24(3):353–9.

    CAS  PubMed  Google Scholar 

  40. Simonneau G, Rubin LJ, Galie N, Barst RJ, Fleming TR, Frost AE, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. 2008;149(8):521–30.

    PubMed  Google Scholar 

  41. McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF, et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol. 2010;55(18):1915–22.

    CAS  PubMed  Google Scholar 

  42. Tapson VF, Torres F, Kermeen F, Keogh AM, Allen RP, Frantz RP, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012;142(6):1383–90.

    CAS  PubMed  Google Scholar 

  43. Sitbon O, Jais X, Savale L, Dauphin C, Natali D, O'Callaghan D, et al. Upfront triple combination therapy of IV epoprostenol with oral bosentan and sildenafil in idiopathic and heritable pulmonary arterial hypertension. Am J Respir Crit Care Med. 2011;183.

    Google Scholar 

  44. Sitbon O, Humbert M, Jagot JL, Taravella O, Fartoukh M, Parent F, et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J. 1998;12(2):265–70.

    CAS  PubMed  Google Scholar 

  45. Sitbon O, Humbert M, Jais X, Ioos V, Hamid AM, Provencher S, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111(23):3105–11.

    CAS  PubMed  Google Scholar 

  46. Malhotra R, Hess D, Lewis GD, Bloch KD, Waxman AB, Semigran MJ. Vasoreactivity to inhaled nitric oxide with oxygen predicts long-term survival in pulmonary arterial hypertension. Pulm Circ. 2011;1(2):250–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the 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 the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30(20):2493–537.

    PubMed  Google Scholar 

  48. Galie N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60–72.

    PubMed  Google Scholar 

  49. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, 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. J Am Coll Cardiol. 2009;53(17):1573–619.

    PubMed  Google Scholar 

  50. Johnson SR, Mehta S, Granton JT. Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review. Eur Respir J. 2006;28(5):999–1004.

    CAS  PubMed  Google Scholar 

  51. Johnson SR, Granton JT, Mehta S. Thrombotic arteriopathy and anticoagulation in pulmonary hypertension. Chest. 2006;130(2):545–52.

    CAS  PubMed  Google Scholar 

  52. Mathur PN, Powles P, Pugsley SO, McEwan MP, Campbell EJ. Effect of digoxin on right ventricular function in severe chronic airflow obstruction. A controlled clinical trial. Ann Intern Med. 1981;95(3):283–8.

    CAS  PubMed  Google Scholar 

  53. Rich S, Seidlitz M, Dodin E, Osimani D, Judd D, Genthner D, et al. The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest. 1998;114(3):787–92.

    CAS  PubMed  Google Scholar 

  54. Ghofrani HA, Voswinckel R, Reichenberger F, Weissmann N, Schermuly RT, Seeger W, et al. Hypoxia- and non-hypoxia-related pulmonary hypertension – established and new therapies. Cardiovasc Res. 2006;72(1):30–40.

    CAS  PubMed  Google Scholar 

  55. Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376–87.

    PubMed  Google Scholar 

  56. Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chang PJ, Chau VQ, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med. 2010;182(5):652–60.

    CAS  PubMed  Google Scholar 

  57. So PP, Davies RA, Chandy G, Stewart D, Beanlands RS, Haddad H, et al. Usefulness of beta-blocker therapy and outcomes in patients with pulmonary arterial hypertension. Am J Cardiol. 2012;109(10):1504–9.

    CAS  PubMed  Google Scholar 

  58. Hansdottir S, Groskreutz DJ, Gehlbach BK. WHO’s in second? a practical review of World Health Organization Group 2 pulmonary hypertension. Chest. 2013;144(2):638–50.

    PubMed Central  PubMed  Google Scholar 

  59. Provencher S, Herve P, Jais X, Lebrec D, Humbert M, Simonneau G, et al. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology. 2006;130(1):120–6.

    CAS  PubMed  Google Scholar 

  60. Tongers J, Schwerdtfeger B, Klein G, Kempf T, Schaefer A, Knapp JM, et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J. 2007;153(1):127–32.

    PubMed  Google Scholar 

  61. MRC. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981;1(8222):681–6.

    Google Scholar 

  62. NOTT. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93(3):391–8.

    Google Scholar 

  63. Weitzenblum E, Sautegeau A, Ehrhart M, Mammosser M, Pelletier A. Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1985;131(4):493–8.

    CAS  PubMed  Google Scholar 

  64. Ashutosh K, Mead G, Dunsky M. Early effects of oxygen administration and prognosis in chronic obstructive pulmonary disease and cor pulmonale. Am Rev Respir Dis. 1983;127(4):399–404.

    CAS  PubMed  Google Scholar 

  65. National Clinical Guideline Centre. Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre; 2010. Available from: http://guidance.nice.org.uk/CG101/Guidance/pdf/English.

    Google Scholar 

  66. NICE. National Institute for Health and Care Excellence. Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update). Clinical guidelines, CG101 – Issued: June 2010. 2010.

    Google Scholar 

  67. Rafanan AL, Golish JA, Dinner DS, Hague LK, Arroliga AC. Nocturnal hypoxemia is common in primary pulmonary hypertension. Chest. 2001;120(3):894–9.

    CAS  PubMed  Google Scholar 

  68. Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, et al. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006;114(14):1482–9.

    PubMed  Google Scholar 

  69. Grunig E, Lichtblau M, Ehlken N, Ghofrani HA, Reichenberger F, Staehler G, et al. Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J. 2012;40(1):84–92.

    PubMed  Google Scholar 

  70. Chan L, Chin LM, Kennedy M, Woolstenhulme JG, Nathan SD, Weinstein AA, et al. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest. 2013;143(2):333–43.

    PubMed Central  PubMed  Google Scholar 

  71. Weinstein AA, Chin LM, Keyser RE, Kennedy M, Nathan SD, Woolstenhulme JG, et al. Effect of aerobic exercise training on fatigue and physical activity in patients with pulmonary arterial hypertension. Respir Med. 2013;107(5):778–84.

    PubMed Central  PubMed  Google Scholar 

  72. Souza R, Humbert M, Sztrymf B, Jais X, Yaici A, Le Pavec J, et al. Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases. Eur Respir J. 2008;31(2):343–8.

    CAS  PubMed  Google Scholar 

  73. Montani D, Savale L, Natali D, Jais X, Herve P, Garcia G, et al. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. Eur Heart J. 2010;31(15):1898–907.

    CAS  PubMed  Google Scholar 

  74. Denton CP, Pope JE, Peter HH, Gabrielli A, Boonstra A, van den Hoogen FH, et al. Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis. 2008;67(9):1222–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000;132(6):425–34.

    CAS  PubMed  Google Scholar 

  76. Jais X, Launay D, Yaici A, Le Pavec J, Tcherakian C, Sitbon O, et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 2008;58(2):521–31.

    PubMed  Google Scholar 

  77. Overbeek MJ, Vonk MC, Boonstra A, Voskuyl AE, Vonk-Noordegraaf A, Smit EF, et al. Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy. Eur Respir J. 2009;34(2):371–9.

    CAS  PubMed  Google Scholar 

  78. Gingo MR, Morris A. Pathogenesis of HIV and the lung. Curr HIV/AIDS Rep. 2013;10(1):42–50.

    PubMed Central  PubMed  Google Scholar 

  79. Zuber JP, Calmy A, Evison JM, Hasse B, Schiffer V, Wagels T, et al. Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy. Clin Infect Dis Off Publ Infect Dis Soc Am. 2004;38(8):1178–85.

    Google Scholar 

  80. Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, et al. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med. 1997;155(3):990–5.

    CAS  PubMed  Google Scholar 

  81. Degano B, Guillaume M, Savale L, Montani D, Jais X, Yaici A, et al. HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era. AIDS (London, England). 2010;24(1):67–75.

    Google Scholar 

  82. Aschmann YZ, Kummer O, Linka A, Wenk M, Azzola A, Bodmer M, et al. Pharmacokinetics and pharmacodynamics of sildenafil in a patient treated with human immunodeficiency virus protease inhibitors. Ther Drug Monit. 2008;30(1):130–4.

    PubMed  Google Scholar 

  83. Chinello P, Cicalini S, Pichini S, Pacifici R, Tempestilli M, Petrosillo N. Sildenafil plasma concentrations in two HIV patients with pulmonary hypertension treated with ritonavir-boosted protease inhibitors. Curr HIV Res. 2012;10(2):162–4.

    CAS  PubMed  Google Scholar 

  84. McRae MP, Lowe CM, Tian X, Bourdet DL, Ho RH, Leake BF, et al. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J Pharmacol Exp Ther. 2006;318(3):1068–75.

    CAS  PubMed  Google Scholar 

  85. Dingemanse J, van Giersbergen PL, Patat A, Nilsson PN. Mutual pharmacokinetic interactions between bosentan and lopinavir/ritonavir in healthy participants. Antivir Ther. 2010;15(2):157–63.

    CAS  PubMed  Google Scholar 

  86. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services. Federal register October 2011. p. 1–167. Available from: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

  87. Bristol-Myers Squibb Canada. Reytaz (atazanavir) Product monograph. Montreal; 2011.

    Google Scholar 

  88. Sitbon O, Gressin V, Speich R, Macdonald PS, Opravil M, Cooper DA, et al. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004;170(11):1212–7.

    PubMed  Google Scholar 

  89. Barbaro G, Lucchini A, Pellicelli AM, Grisorio B, Giancaspro G, Barbarini G. Highly active antiretroviral therapy compared with HAART and bosentan in combination in patients with HIV-associated pulmonary hypertension. Heart (British Cardiac Society). 2006;92(8):1164–6.

    CAS  Google Scholar 

  90. Nunes H, Humbert M, Sitbon O, Morse JH, Deng Z, Knowles JA, et al. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2003;167(10):1433–9.

    PubMed  Google Scholar 

  91. Aguilar RV, Farber HW. Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med. 2000;162(5):1846–50.

    CAS  PubMed  Google Scholar 

  92. Petitpretz P, Brenot F, Azarian R, Parent F, Rain B, Herve P, et al. Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension. Circulation. 1994;89(6):2722–7.

    CAS  PubMed  Google Scholar 

  93. Cea-Calvo L, Escribano Subias P, Tello de Menesses R, Lazaro Salvador M, Gomez Sanchez MA, Delgado Jimenez JF, et al. Treatment of HIV-associated pulmonary hypertension with treprostinil. Rev Esp Cardiol. 2003;56(4):421–5.

    PubMed  Google Scholar 

  94. Ghofrani HA, Friese G, Discher T, Olschewski H, Schermuly RT, Weissmann N, et al. Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension. Eur Respir J. 2004;23(2):321–6.

    CAS  PubMed  Google Scholar 

  95. Hadengue A, Benhayoun MK, Lebrec D, Benhamou JP. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology. 1991;100(2):520–8.

    CAS  PubMed  Google Scholar 

  96. Ramsay MA, Simpson BR, Nguyen AT, Ramsay KJ, East C, Klintmalm GB. Severe pulmonary hypertension in liver transplant candidates. Liver Transpl Surg Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc. 1997;3(5):494–500.

    CAS  Google Scholar 

  97. Pellicelli AM, Barbaro G, Puoti C, Guarascio P, Lusi EA, Bellis L, et al. Plasma cytokines and portopulmonary hypertension in patients with cirrhosis waiting for orthotopic liver transplantation. Angiology. 2010;61(8):802–6.

    CAS  PubMed  Google Scholar 

  98. Hoeper MM, Halank M, Marx C, Hoeffken G, Seyfarth HJ, Schauer J, et al. Bosentan therapy for portopulmonary hypertension. Eur Respir J. 2005;25(3):502–8.

    CAS  PubMed  Google Scholar 

  99. Kuo PC, Johnson LB, Plotkin JS, Howell CD, Bartlett ST, Rubin LJ. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation. 1997;63(4):604–6.

    CAS  PubMed  Google Scholar 

  100. Reichenberger F, Voswinckel R, Steveling E, Enke B, Kreckel A, Olschewski H, et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J. 2006;28(3):563–7.

    CAS  PubMed  Google Scholar 

  101. Findlay JY, Plevak DJ, Krowka MJ, Sack EM, Porayko MK. Progressive splenomegaly after epoprostenol therapy in portopulmonary hypertension. Liver Transpl Surg Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc. 1999;5(5):362–5.

    CAS  Google Scholar 

  102. Savale L, Magnier R, Le Pavec J, Jais X, Montani D, O’Callaghan DS, et al. Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension. Eur Respir J. 2013;41(1):96–103.

    CAS  PubMed  Google Scholar 

  103. Schott R, Chaouat A, Launoy A, Pottecher T, Weitzenblum E. Improvement of pulmonary hypertension after liver transplantation. Chest. 1999;115(6):1748–9.

    CAS  PubMed  Google Scholar 

  104. Beghetti M, Galie N. Eisenmenger syndrome a clinical perspective in a new therapeutic era of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;53(9):733–40.

    PubMed  Google Scholar 

  105. Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114(1):48–54.

    CAS  PubMed  Google Scholar 

  106. Chau EM, Fan KY, Chow WH. Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension. Int J Cardiol. 2007;120(3):301–5.

    PubMed  Google Scholar 

  107. Beciani E, Palazzini M, Bulatovic I, Mazzanti G, Gotti E, Marinelli A, et al. Effects of sildenafil treatment in patients with pulmonary hypertension associated with congenital cardiac shunts. Am J Respir Crit Care Med. 2010;181.

    Google Scholar 

  108. Dimopoulos K, Inuzuka R, Goletto S, Giannakoulas G, Swan L, Wort SJ, et al. Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Circulation. 2010;121(1):20–5.

    PubMed  Google Scholar 

  109. Sandoval J, Aguirre JS, Pulido T, Martinez-Guerra ML, Santos E, Alvarado P, et al. Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am J Respir Crit Care Med. 2001;164(9):1682–7.

    CAS  PubMed  Google Scholar 

  110. Lapa M, Dias B, Jardim C, Fernandes CJ, Dourado PM, Figueiredo M, et al. Cardiopulmonary manifestations of hepatosplenic schistosomiasis. Circulation. 2009;119(11):1518–23.

    PubMed  Google Scholar 

  111. Correa Rde A, Moreira MV, Saraiva JM, Mancuzo EV, Silva LC, Lambertucci JR. Treatment of schistosomiasis-associated pulmonary hypertension. Jornal brasileiro de pneumologia publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2011;37(2):272–6.

    PubMed  Google Scholar 

  112. Graham BB, Bandeira AP, Morrell NW, Butrous G, Tuder RM. Schistosomiasis-associated pulmonary hypertension: pulmonary vascular disease: the global perspective. Chest. 2010;137(6 Suppl):20s–9.

    PubMed  Google Scholar 

  113. Fernandes CJ, Dias BA, Jardim CV, Hovnanian A, Hoette S, Morinaga LK, et al. The role of target therapies in schistosomiasis-associated pulmonary arterial hypertension. Chest. 2012;141(4):923–8.

    PubMed  Google Scholar 

  114. Palmer SM, Robinson LJ, Wang A, Gossage JR, Bashore T, Tapson VF. Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease. Chest. 1998;113(1):237–40.

    CAS  PubMed  Google Scholar 

  115. Okumura H, Nagaya N, Kyotani S, Sakamaki F, Nakanishi N, Fukuhara S, et al. Effects of continuous IV prostacyclin in a patient with pulmonary veno-occlusive disease. Chest. 2002;122(3):1096–8.

    PubMed  Google Scholar 

  116. Montani D, Jais X, Price LC, Achouh L, Degano B, Mercier O, et al. Cautious epoprostenol therapy is a safe bridge to lung transplantation in pulmonary veno-occlusive disease. Eur Respir J. 2009;34(6):1348–56.

    CAS  PubMed  Google Scholar 

  117. Sanderson JE, Spiro SG, Hendry AT, Turner-Warwick M. A case of pulmonary veno-occlusive disease respondong to treatment with azathioprine. Thorax. 1977;32(2):140–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Califf RM, Adams KF, McKenna WJ, Gheorghiade M, Uretsky BF, McNulty SE, 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(1):44–54.

    CAS  PubMed  Google Scholar 

  119. Ferguson JJ. Meeting highlights: highlights of the 51st annual scientific sessions of the American College of Cardiology. Atlanta, Georgia, USA. March 17–20, 2002. Circulation. 2002;106(7):E24–30.

    PubMed  Google Scholar 

  120. Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124(2):164–74.

    CAS  PubMed  Google Scholar 

  121. Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007;116(14):1555–62.

    CAS  PubMed  Google Scholar 

  122. Madden BP, Allenby M, Loke TK, Sheth A. A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vascul Pharmacol. 2006;44(5):372–6.

    CAS  PubMed  Google Scholar 

  123. Blanco I, Gimeno E, Munoz PA, Pizarro S, Gistau C, Rodriguez-Roisin R, et al. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am J Respir Crit Care Med. 2010;181(3):270–8.

    CAS  PubMed  Google Scholar 

  124. Rao RS, Singh S, Sharma BB, Agarwal VV, Singh V. Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Indian J Chest Dis Allied Sci. 2011;53(2):81–5.

    PubMed  Google Scholar 

  125. Shujaat A, Bajwa AA, Cury JD. Pulmonary hypertension secondary to COPD. Pulm Med. 2012;2012:203952.

    PubMed Central  PubMed  Google Scholar 

  126. Lee TM, Chen CC, Shen HN, Chang NC. Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Clin Sci (London, England: 1979). 2009;116(6):497–505.

    CAS  Google Scholar 

  127. Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002;360(9337):895–900.

    CAS  PubMed  Google Scholar 

  128. Olschewski H, Ghofrani HA, Walmrath D, Schermuly R, Temmesfeld-Wollbruck B, Grimminger F, et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med. 1999;160(2):600–7.

    CAS  PubMed  Google Scholar 

  129. King Jr TE, Behr J, Brown KK, du Bois RM, Lancaster L, de Andrade JA, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;177(1):75–81.

    CAS  PubMed  Google Scholar 

  130. King Jr TE, Brown KK, Raghu G, du Bois RM, Lynch DA, Martinez F, et al. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184(1):92–9.

    PubMed  Google Scholar 

  131. Seibold JR, Denton CP, Furst DE, Guillevin L, Rubin LJ, Wells A, et al. Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. Arthritis Rheum. 2010;62(7):2101–8.

    CAS  PubMed  Google Scholar 

  132. Arias MA, Garcia-Rio F, Alonso-Fernandez A, Martinez I, Villamor J. Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study. Eur Heart J. 2006;27(9):1106–13.

    PubMed  Google Scholar 

  133. Sugerman HJ, Baron PL, Fairman RP, Evans CR, Vetrovec GW. Hemodynamic dysfunction in obesity hypoventilation syndrome and the effects of treatment with surgically induced weight loss. Ann Surg. 1988;207(5):604–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  134. Fedullo P, Kerr KM, Kim NH, Auger WR. Chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2011;183(12):1605–13.

    PubMed  Google Scholar 

  135. Jais X, D’Armini AM, Jansa P, Torbicki A, Delcroix M, Ghofrani HA, et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol. 2008;52(25):2127–34.

    CAS  PubMed  Google Scholar 

  136. Becattini C, Manina G, Busti C, Gennarini S, Agnelli G. Bosentan for chronic thromboembolic pulmonary hypertension: findings from a systematic review and meta-analysis. Thromb Res. 2010;126(1):e51–6.

    CAS  PubMed  Google Scholar 

  137. Sheth A, Park JE, Ong YE, Ho TB, Madden BP. Early haemodynamic benefit of sildenafil in patients with coexisting chronic thromboembolic pulmonary hypertension and left ventricular dysfunction. Vascul Pharmacol. 2005;42(2):41–5.

    CAS  PubMed  Google Scholar 

  138. Suntharalingam J, Treacy CM, Doughty NJ, Goldsmith K, Soon E, Toshner MR, et al. Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest. 2008;134(2):229–36.

    CAS  PubMed  Google Scholar 

  139. Cabrol S, Souza R, Jais X, Fadel E, Ali RH, Humbert M, et al. Intravenous epoprostenol in inoperable chronic thromboembolic pulmonary hypertension. J Heart Lung Transpl Off Publ Int Soc Heart Transpl. 2007;26(4):357–62.

    Google Scholar 

  140. Skoro-Sajer N, Bonderman D, Wiesbauer F, Harja E, Jakowitsch J, Klepetko W, et al. Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. J Thromb Haemost JTH. 2007;5(3):483–9.

    CAS  PubMed  Google Scholar 

  141. Nagaya N, Sasaki N, Ando M, Ogino H, Sakamaki F, Kyotani S, et al. Prostacyclin therapy before pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension. Chest. 2003;123(2):338–43.

    CAS  PubMed  Google Scholar 

  142. Jensen KW, Kerr KM, Fedullo PF, Kim NH, Test VJ, Ben-Yehuda O, et al. Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary hypertension before pulmonary thromboendarterectomy. Circulation. 2009;120(13):1248–54.

    PubMed  Google Scholar 

  143. Condliffe R, Kiely DG, Gibbs JS, Corris PA, Peacock AJ, Jenkins DP, et al. Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2008;177(10):1122–7.

    PubMed  Google Scholar 

  144. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.

    PubMed  Google Scholar 

  145. Miller AC, Gladwin MT. Pulmonary complications of sickle cell disease. Am J Respir Crit Care Med. 2012;185(11):1154–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Morris CR, Morris Jr SM, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, et al. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003;168(1):63–9.

    PubMed  Google Scholar 

  147. Nunes H, Humbert M, Capron F, Brauner M, Sitbon O, Battesti JP, et al. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax. 2006;61(1):68–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Corte TJ, Wells AU, Nicholson AG, Hansell DM, Wort SJ. Pulmonary hypertension in sarcoidosis: a review. Respirology (Carlton, Vic). 2011;16(1):69–77.

    Google Scholar 

  149. Fisher KA, Serlin DM, Wilson KC, Walter RE, Berman JS, Farber HW. Sarcoidosis-associated pulmonary hypertension: outcome with long-term epoprostenol treatment. Chest. 2006;130(5):1481–8.

    CAS  PubMed  Google Scholar 

  150. Milman N, Burton CM, Iversen M, Videbaek R, Jensen CV, Carlsen J. Pulmonary hypertension in end-stage pulmonary sarcoidosis: therapeutic effect of sildenafil? J Heart Lung Transpl Off Publ Int Soc Heart Transpl. 2008;27(3):329–34.

    Google Scholar 

  151. Baughman RP, Culver DA, Cordova FC, Padilla M, Gibson KF, Lower EE, et al. Bosentan for sarcoidosis associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest. 2014;145(4):810–7.

    CAS  PubMed  Google Scholar 

  152. Barnett CF, Bonura EJ, Nathan SD, Ahmad S, Shlobin OA, Osei K, et al. Treatment of sarcoidosis-associated pulmonary hypertension. A two-center experience. Chest. 2009;135(6):1455–61.

    PubMed Central  PubMed  Google Scholar 

  153. Shrikrishna D, Coker RK. Managing passengers with stable respiratory disease planning air travel: British Thoracic Society recommendations. Thorax. 2011;66(9):831–3.

    PubMed  Google Scholar 

  154. Madden BP. Pulmonary hypertension and pregnancy. Int J Obstet Anesth. 2009;18(2):156–64.

    CAS  PubMed  Google Scholar 

  155. Clapp 3rd JF, Capeless E. Cardiovascular function before, during, and after the first and subsequent pregnancies. Am J Cardiol. 1997;80(11):1469–73.

    PubMed  Google Scholar 

  156. Daliento L, Somerville J, Presbitero P, Menti L, Brach-Prever S, Rizzoli G, et al. Eisenmenger syndrome. Factors relating to deterioration and death. Eur Heart J. 1998;19(12):1845–55.

    CAS  PubMed  Google Scholar 

  157. Kiely DG, Condliffe R, Webster V, Mills GH, Wrench I, Gandhi SV, et al. Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach. BJOG. 2010;117(5):565–74.

    CAS  PubMed  Google Scholar 

  158. Goland S, Tsai F, Habib M, Janmohamed M, Goodwin TM, Elkayam U. Favorable outcome of pregnancy with an elective use of epoprostenol and sildenafil in women with severe pulmonary hypertension. Cardiology. 2010;115(3):205–8.

    PubMed  Google Scholar 

  159. Gurakan B, Kayiran P, Ozturk N, Kayiran SM, Dindar A. Therapeutic combination of sildenafil and iloprost in a preterm neonate with pulmonary hypertension. Pediatr Pulmonol. 2011;46(6):617–20.

    PubMed  Google Scholar 

  160. Villanueva-Garcia D, Mota-Rojas D, Hernandez-Gonzalez R, Sanchez-Aparicio P, Alonso-Spilsbury M, Trujillo-Ortega ME, et al. A systematic review of experimental and clinical studies of sildenafil citrate for intrauterine growth restriction and pre-term labour. J Obstet Gynaecol J Institute Obstet Gynaecol. 2007;27(3):255–9.

    CAS  Google Scholar 

  161. Lacassie HJ, Germain AM, Valdes G, Fernandez MS, Allamand F, Lopez H. Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine. Obstet Gynecol. 2004;103(5 Pt 2):1118–20.

    PubMed  Google Scholar 

  162. Iacovidou N, Syggelou A, Fanos V, Xanthos T. The use of sildenafil in the treatment of persistent pulmonary hypertension of the newborn: a review of the literature. Curr Pharm Des. 2012;18(21):3034–45.

    CAS  PubMed  Google Scholar 

  163. Elliot CA, Stewart P, Webster VJ, Mills GH, Hutchinson SP, Howarth ES, et al. The use of iloprost in early pregnancy in patients with pulmonary arterial hypertension. Eur Respir J. 2005;26(1):168–73.

    CAS  PubMed  Google Scholar 

  164. Cotrim SC, Loureiro MJ, Avillez T, Simoes O, Cordeiro P, Almeida S, et al. Three cases of pregnancy in patients with severe pulmonary arterial hypertension: experience of a single unit. Rev Port Cardiol. 2010;29(1):95–103.

    PubMed  Google Scholar 

  165. Badalian SS, Silverman RK, Aubry RH, Longo J. Twin pregnancy in a woman on long-term epoprostenol therapy for primary pulmonary hypertension. A case report. J Reprod Med. 2000;45(2):149–52.

    CAS  PubMed  Google Scholar 

  166. Avdalovic M, Sandrock C, Hoso A, Allen R, Albertson TE. Epoprostenol in pregnant patients with secondary pulmonary hypertension: two case reports and a review of the literature. Treat Respir Med. 2004;3(1):29–34.

    PubMed  Google Scholar 

  167. Kiss H, Egarter C, Asseryanis E, Putz D, Kneussl M. Primary pulmonary hypertension in pregnancy: a case report. Am J Obstet Gynecol. 1995;172(3):1052–4.

    CAS  PubMed  Google Scholar 

  168. Magee LA, Schick B, Donnenfeld AE, Sage SR, Conover B, Cook L, et al. The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. Am J Obstet Gynecol. 1996;174(3):823–8.

    CAS  PubMed  Google Scholar 

  169. Budts W, Van Pelt N, Gillyns H, Gewillig M, Van De Werf F, Janssens S. Residual pulmonary vasoreactivity to inhaled nitric oxide in patients with severe obstructive pulmonary hypertension and Eisenmenger syndrome. Heart (British Cardiac Society). 2001;86(5):553–8.

    CAS  Google Scholar 

  170. Leuchte HH, Schwaiblmair M, Baumgartner RA, Neurohr CF, Kolbe T, Behr J. Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension. Chest. 2004;125(2):580–6.

    CAS  PubMed  Google Scholar 

  171. Ulrich S, Fischler M, Speich R, Popov V, Maggiorini M. Chronic thromboembolic and pulmonary arterial hypertension share acute vasoreactivity properties. Chest. 2006;130(3):841–6.

    PubMed  Google Scholar 

  172. Goodwin TM, Gherman RB, Hameed A, Elkayam U. Favorable response of Eisenmenger syndrome to inhaled nitric oxide during pregnancy. Am J Obstet Gynecol. 1999;180(1 Pt 1):64–7.

    CAS  PubMed  Google Scholar 

  173. Lam GK, Stafford RE, Thorp J, Moise Jr KJ, Cairns BA. Inhaled nitric oxide for primary pulmonary hypertension in pregnancy. Obstet Gynecol. 2001;98(5 Pt 2):895–8.

    CAS  PubMed  Google Scholar 

  174. Madsen KM, Neerhof MG, Wessale JL, Thaete LG. Influence of ET(B) receptor antagonism on pregnancy outcome in rats. J Soc Gynecol Investig. 2001;8(4):239–44.

    CAS  PubMed  Google Scholar 

  175. Bedard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J. 2009;30(3):256–65.

    PubMed  Google Scholar 

  176. Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996. J Am Coll Cardiol. 1998;31(7):1650–7.

    CAS  PubMed  Google Scholar 

  177. Martinez MV, Rutherford JD. Pulmonary hypertension in pregnancy. Cardiol Rev. 2013;21(4):167–73.

    PubMed  Google Scholar 

  178. Galie N, Palazzini M, Manes A. Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses. Eur Heart J. 2010;31(17):2080–6.

    PubMed Central  PubMed  Google Scholar 

  179. Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–40.

    CAS  PubMed  Google Scholar 

  180. Ghofrani HA, D’Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369(4):319–29.

    CAS  PubMed  Google Scholar 

  181. Bonderman D, Ghio S, Felix SB, Ghofrani HA, Michelakis E, Mitrovic V, et al. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation. 2013;128(5):502–11.

    CAS  PubMed  Google Scholar 

  182. Hoeper MM, Halank M, Wilkens H, Gunther A, Weimann G, Gebert I, et al. Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial. Eur Respir J. 2013;41(4):853–60.

    PubMed  Google Scholar 

  183. Ghofrani HA, Staehler G, Gruenig E, Halank M, Mitrovic V, Unger S, et al. The Effect of the soluble guanylate cyclase stimulator riociguat on hemodynamics in patients with pulmonary hypertension due to chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183.

    Google Scholar 

  184. Simonneau G, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N, et al. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012;40(4):874–80.

    CAS  PubMed  Google Scholar 

  185. Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, et al. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013;127(10):1128–38.

    CAS  PubMed  Google Scholar 

  186. Gomberg-Maitland M, Maitland ML, Barst RJ, Sugeng L, Coslet S, Perrino TJ, et al. A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension. Clin Pharmacol Ther. 2010;87(3):303–10.

    CAS  PubMed Central  PubMed  Google Scholar 

  187. Galie N, Badesch D, Fleming T, Simonneau G, Rubin L, Ewert R, et al. Effects of inhaled aviptadil (vasoactive intestinal peptide) in patients with pulmonary arterial hypertension (PAH): results from a phase II study. Eur Heart J. 2010;31:22.

    Google Scholar 

  188. Nagaya N, Kyotani S, Uematsu M, Ueno K, Oya H, Nakanishi N, et al. Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension. Circulation. 2004;109(3):351–6.

    PubMed  Google Scholar 

  189. Fujita H, Fukumoto Y, Saji K, Sugimura K, Demachi J, Nawata J, et al. Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension. Heart Vessels. 2010;25(2):144–9.

    PubMed  Google Scholar 

  190. Wilkins MR, Ali O, Bradlow W, Wharton J, Taegtmeyer A, Rhodes CJ, et al. Simvastatin as a treatment for pulmonary hypertension trial. Am J Respir Crit Care Med. 2010;181(10):1106–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  191. Kawut SM, Bagiella E, Lederer DJ, Shimbo D, Horn EM, Roberts KE, et al. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation. 2011;123(25):2985–93.

    CAS  PubMed Central  PubMed  Google Scholar 

  192. Channick RN, Newhart JW, Johnson FW, Williams PJ, Auger WR, Fedullo PF, et al. Pulsed delivery of inhaled nitric oxide to patients with primary pulmonary hypertension: an ambulatory delivery system and initial clinical tests. Chest. 1996;109(6):1545–9.

    CAS  PubMed  Google Scholar 

  193. Snell GI, Salamonsen RF, Bergin P, Esmore DS, Khan S, Williams TJ. Inhaled nitric oxide used as a bridge to heart-lung transplantation in a patient with end-stage pulmonary hypertension. Am J Respir Crit Care Med. 1995;151(4):1263–6.

    CAS  PubMed  Google Scholar 

  194. Waxman AB, Lawler L, Cornett G. Cicletanine for the treatment of pulmonary arterial hypertension. Arch Intern Med. 2008;168(19):2164–6.

    PubMed  Google Scholar 

  195. Guignabert C, Tu L, Izikki M, Dewachter L, Zadigue P, Humbert M, et al. Dichloroacetate treatment partially regresses established pulmonary hypertension in mice with SM22alpha-targeted overexpression of the serotonin transporter. FASEB J Off Publ Federation Am Soc Exp Biol. 2009;23(12):4135–47.

    CAS  Google Scholar 

  196. Seferian A, Simonneau G. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow? Eur Respir Rev Off J Eur Respir Soc. 2013;22(129):217–26.

    Google Scholar 

  197. Diller GP, Thum T, Wilkins MR, Wharton J. Endothelial progenitor cells in pulmonary arterial hypertension. Trends Cardiovasc Med. 2010;20(1):22–9.

    CAS  PubMed  Google Scholar 

  198. Wang XX, Zhang FR, Shang YP, Zhu JH, Xie XD, Tao QM, et al. Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial. J Am Coll Cardiol. 2007;49(14):1566–71.

    CAS  PubMed  Google Scholar 

  199. Reynolds AM, Holmes MD, Danilov SM, Reynolds PN. Targeted gene delivery of BMPR2 attenuates pulmonary hypertension. Eur Respir J. 2012;39(2):329–43.

    CAS  PubMed  Google Scholar 

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    Adam Loveridge & Jenny Bacon

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Loveridge, A., Bacon, J., Madden, B. (2015). Current Treatment Strategies, Guidelines and New Therapies. In: Madden, B. (eds) Treatment of Pulmonary Hypertension. Current Cardiovascular Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13581-6_3

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