Руководящие центры легочной гипертензии

ЛАГ - редкая болезнь с высокой смертностью. Учитывая сложную природу этой болезни, если вообще это возможно, большинство пациентов должно лечиться в (или с участием) руководящих центров ЛАГ. В центрах, которые специализируются по ЛАГ, работают опытные врачи-эксперты,, сестринский персонал, специально обученный для помощи при лечении пациентов с ЛАГ, часто проводятся клинические испытания новых препаратов. Мультидисциплинарные программы набирают для экспертизы кардиологов, пульмонологов, и обычно ревматологов, гепатологов, инфекционистов, гематологов, трансплантологов, психологов и социальных работников.

Ссылки

1. Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial

hypertension in France: results from a national registry. Am J Respir

Crit Care Med. 2006;173:1023–30.

2. Thenappan T, Shah SJ, Rich S, et al. A USA-based registry for

pulmonary arterial hypertension: 1982–2006. Eur Respir J. 2007;30:

1103–10.

3. McGoon M, Gutterman D, Steen V, et al. Screening, early detection,

and diagnosis of pulmonary arterial hypertension: ACCP evidencebased

clinical practice guidelines. Chest. 2004;126:14S–34S.

4. Friedman WF. Proceedings of National Heart, Lung, and Blood

Institute pediatric cardiology workshop: pulmonary hypertension.

Pediatr Res. 1986;20:811–24.

5. Voelkel NF, Quaife RA, Leinwand LA, et al. Right ventricular

function and failure: report of a National Heart, Lung, and Blood

Institute working group on cellular and molecular mechanisms of

right heart failure. Circulation. 2006;114:1883–91.

6. 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;327:76–81.

7. Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium

channel blockers in idiopathic pulmonary arterial hypertension.

Circulation. 2005;111:3105–11.

8. Archer S, Rich S. Primary pulmonary hypertension: a vascular

biology and translational research “Work in progress.” Circulation.

2000;102:2781–91.

9. Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl

J Med. 2004;351:1655– 65.

10. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension.

A national prospective study. Ann Intern Med. 1987;107:

216–23.

11. Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary

hypertension (gene PPH1) is caused by mutations in the bone

morphogenetic protein receptor-II gene. Am J Hum Genet. 2000;

67:737– 44.

12. Lane KB, Machado RD, Pauciulo MW, et al. Heterozygous germline

mutations in BMPR2, encoding a TGF-beta receptor, cause

familial primary pulmonary hypertension. The International PPH

Consortium. Nat Genet. 2000;26:81– 4.

13. Trembath RC, Thomson JR, Machado RD, et al. Clinical and molecular

genetic features of pulmonary hypertension in patients with hereditary

hemorrhagic telangiectasia. N Engl J Med. 2001;345:325–34.

14. Guignabert C, Izikki M, Tu LI, et al. Transgenic mice overexpressing

the 5-hydroxytryptamine transporter gene in smooth muscle

develop pulmonary hypertension. Circ Res. 2006;98:1323–30.

15. West J, Fagan K, Steudel W, et al. Pulmonary hypertension in

transgenic mice expressing a dominant-negative BMPRII gene in

smooth muscle. Circ Res. 2004;94:1109 –14.

16. Herve P, Launay JM, Scrobohaci ML, et al. Increased plasma

serotonin in primary pulmonary hypertension. Am J Med. 1995;99:

249–54.

17. Christman BW, McPherson CD, Newman JH, et al. An imbalance

between the excretion of thromboxane and prostacyclin metabolites

in pulmonary hypertension. N Engl J Med. 1992;327:70 –5.

18. Giaid A, Yanagisawa M, Langleben D, et al. Expression of

endothelin-1 in the lungs of patients with pulmonary hypertension.

N Engl J Med. 1993;328:1732–9.

19. Stewart DJ, Levy RD, Cernacek P, et al. Increased plasma

endothelin-1 in pulmonary hypertension: marker or mediator of

disease? Ann Intern Med. 1991;114:464 –9.

20. Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase

expression is decreased in lungs from patients with severe pulmonary

hypertension. Am J Respir Crit Care Med. 1999;159:1925–32.

21. Rubens C, Ewert R, Halank M, et al. Big endothelin-1 and

endothelin-1 plasma levels are correlated with the severity of primary

pulmonary hypertension. Chest. 2001;120:1562–9.

22. Steudel W, Ichinose F, Huang PL, et al. Pulmonary vasoconstriction

and hypertension in mice with targeted disruption of the endothelial

nitric oxide synthase (NOS 3) gene. Circ Res. 1997;81:34–41.

23. Eddahibi S, Humbert M, Fadel E, et al. Serotonin transporter

overexpression is responsible for pulmonary artery smooth muscle

hyperplasia in primary pulmonary hypertension. J Clin Invest. 2001;

108:1141–50.

24. Marcos E, Adnot S, Pham MH, et al. Serotonin transporter

inhibitors protect against hypoxic pulmonary hypertension. Am J

Respir Crit Care Med. 2003;168:487–93.

25. Petkov V, Mosgoeller W, Ziesche R, et al. Vasoactive intestinal

peptide as a new drug for treatment of primary pulmonary hypertension.

J Clin Invest. 2003;111:1339–46.

26. Eddahibi S, Morrell N, d’Ortho MP, et al. Pathobiology of pulmonary

arterial hypertension. Eur Respir J. 2002;20:1559 –72.

27. Bonnet S, Michelakis ED, Porter CJ, et al. An abnormal

mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway

disrupts oxygen sensing and triggers pulmonary arterial hypertension

in fawn hooded rats: similarities to human pulmonary arterial

hypertension. Circulation. 2006;113:2630–41.

28. Yuan XJ, Wang J, Juhaszova M, et al. Attenuated K channel gene

transcription in primary pulmonary hypertension. Lancet. 1998;351:

726–7.

29. Bonnet S, Rochefort G, Sutendra G, et al. The nuclear factor of

activated T cells in pulmonary arterial hypertension can be therapeutically

targeted. Proc Natl Acad Sci U S A. 2007;104:11418 –23.

30. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular

pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol.

2004;43:13S–24S.

31. Cowan KN, Jones PL, Rabinovitch M. Elastase and matrix metalloproteinase

inhibitors induce regression, and tenascin-C antisense prevents

progression, of vascular disease. J Clin Invest. 2000;105:21–34.

31a.Yuan JX, Rubin LJ. Pathogenesis of pulmonary arterial hypertension:

the need for multiple hits. Circulation. 2005;111:534 –8.

32. Simonneau G, Galie N, Rubin L, et al. Clinical classification of

pulmonary hypertension. J Am Coll Cardiol. 2004;43 Suppl 1:S5–12.

33. Yigla M, Kramer MR, Bendayan D, et al. Unexplained severe

pulmonary hypertension in the elderly: report on 14 patients. Isr Med

Assoc J. 2004;6:78–81.

34. Cogan JD, Vnencak-Jones CL, Phillips JA III, et al. Gross BMPR2

gene rearrangements constitute a new cause for primary pulmonary

hypertension. Genet Med. 2005;7:169 –74.

35. Machado RD, Pauciulo MW, Thomson JR, et al. BMPR2 haploinsufficiency

as the inherited molecular mechanism for primary pulmonary

hypertension. Am J Hum Genet. 2001;68:92–102.

36. Thomson JR, Machado RD, Pauciulo MW, et al. Sporadic primary

pulmonary hypertension is associated with germline mutations of the

gene encoding BMPR-II, a receptor member of the TGF-beta

family. J Med Genet. 2000;37:741–5.

37. Humbert M, Labrune P, Sitbon O, et al. Pulmonary arterial

hypertension and type-I glycogen-storage disease: the serotonin

hypothesis. Eur Respir J. 2002;20:59–65.

38. Koehler R, Grunig E, Pauciulo MW, et al. Low frequency of BMPR2

mutations in a German cohort of patients with sporadic idiopathic

pulmonary arterial hypertension. J Med Genet. 2004;41:e127.

39. Loyd JE, Butler MG, Foroud TM, et al. Genetic anticipation and

abnormal gender ratio at birth in familial primary pulmonary hypertension.

Am J Respir Crit Care Med. 1995;152:93–7.

40. Sztrymf B, Coulet F, Girerd B, et al. Clinical outcomes of pulmonary

arterial hypertension in carriers of BMPR2 mutation. Am J Respir

Crit Care Med. 2008;177:1377– 83.

41. Hachulla E, Gressin V, Guillevin L, et al. Early detection of

pulmonary arterial hypertension in systemic sclerosis: a French

nationwide prospective multicenter study. Arthritis Rheum. 2005;52:

3792–800.

42. Mukerjee D, St George D, Coleiro B, et al. Prevalence and outcome

in systemic sclerosis associated pulmonary arterial hypertension: application

of a registry approach. Ann Rheum Dis. 2003;62:1088–93.

43. Opravil M, Pechere M, Speich R, et al. HIV-associated primary

pulmonary hypertension. A case control study. Swiss HIV Cohort

Study. Am J Respir Crit Care Med. 1997;155:990 –5.

44. Sitbon O, Lascoux-Combe C, Delfraissy JF, et al. Prevalence of

HIV-related pulmonary arterial hypertension in the current antiretroviral

therapy era. Am J Respir Crit Care Med. 2008;177:108 –13.

45. Speich R, Jenni R, Opravil M, et al. Primary pulmonary hypertension

in HIV infection. Chest. 1991;100:1268 –71.

46. Mehta NJ, Khan IA, Mehta RN, et al. HIV-Related pulmonary

hypertension: analytic review of 131 cases. Chest. 2000;118:1133– 41.

47. McDonnell PJ, Toye PA, Hutchins GM. Primary pulmonary hypertension

and cirrhosis: are they related? Am Rev Respir Dis. 1983;

127:437– 41.

48. Castro M, Krowka MJ, Schroeder DR, et al. Frequency and clinical

implications of increased pulmonary artery pressures in liver transplant

patients. Mayo Clin Proc. 1996;71:543–51.

49. Gurtner HP. Aminorex and pulmonary hypertension. A review. Cor

Vasa. 1985;27:160 –71.

50. Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs

and the risk of primary pulmonary hypertension. International

Primary Pulmonary Hypertension Study Group. N Engl J Med.

1996;335:609 –16.

51. Gomez-Sanchez MA, Saenz de la Calzada C, Gomez-Pajuelo C, et al.

Clinical and pathologic manifestations of pulmonary vascular disease in

the toxic oil syndrome. J Am Coll Cardiol. 1991;18:1539–45.

52. Sack KE, Criswell LA. Eosinophilia-myalgia syndrome: the aftermath.

South Med J. 1992;85:878–82.

53. Albertson TE, Walby WF, Derlet RW. Stimulant-induced pulmonary

toxicity. Chest. 1995;108:1140 –9.

54. Chin KM, Channick RN, Rubin LJ. Is methamphetamine use

associated with idiopathic pulmonary arterial hypertension? Chest.

2006;130:1657– 63.

55. Castro O, Hoque M, Brown BD. Pulmonary hypertension in sickle

cell disease: cardiac catheterization results and survival. Blood. 2003;

101:1257– 61.

56. Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension

as a risk factor for death in patients with sickle cell disease. N Engl

J Med. 2004;350:886 –95.

57. Anthi A, Machado RF, Jison ML, et al. Hemodynamic and functional

assessment of patients with sickle cell disease and pulmonary

hypertension. Am J Respir Crit Care Med. 2007;175:1272–9.

58. Klings ES, Farber HW. Role of free radicals in the pathogenesis of

acute chest syndrome in sickle cell disease. Respir Res. 2001;2:280 –5.

59. Rybicki AC, Benjamin LJ. Increased levels of endothelin-1 in plasma

of sickle cell anemia patients. Blood. 1998;92:2594–6.

60. Aessopos A, Farmakis D, Karagiorga M, et al. Cardiac involvement

in thalassemia intermedia: a multicenter study. Blood. 2001;97:

3411–6.

61. Hayag-Barin JE, Smith RE, Tucker FC, Jr. Hereditary spherocytosis,

thrombocytosis, and chronic pulmonary emboli: a case report and

review of the literature. Am J Hematol. 1998;57:82– 4.

62. Abdalla SA, Gallione CJ, Barst RJ, et al. Primary pulmonary

hypertension in families with hereditary haemorrhagic telangiectasia.

Eur Respir J. 2004;23:373–7.

63. Dingli D, Utz JP, Krowka MJ, et al. Unexplained pulmonary

hypertension in chronic myeloproliferative disorders. Chest. 2001;

120:801– 8.

64. Chu JW, Kao PN, Faul JL, et al. High prevalence of autoimmune

thyroid disease in pulmonary arterial hypertension. Chest. 2002;122:

1668–73.

65. Peacock AJ. Pulmonary hypertension after splenectomy: a consequence

of loss of the splenic filter or is there something more?

Thorax. 2005;60:983– 4.

66. Pietra GG, Capron F, Stewart S, et al. Pathologic assessment of

vasculopathies in pulmonary hypertension. J Am Coll Cardiol.

2004;43:25S–32S.

67. Holcomb BW Jr., Loyd JE, Ely EW, et al. Pulmonary veno-occlusive

disease: a case series and new observations. Chest. 2000;118:1671–9.

68. Okumura H, Nagaya N, Kyotani S, et al. Effects of continuous IV

prostacyclin in a patient with pulmonary veno-occlusive disease.

Chest. 2002;122:1096–8.

69. McLaughlin VV, Presberg KW, Doyle RL, et al. Prognosis of

pulmonary arterial hypertension: ACCP evidence-based clinical practice

guidelines. Chest. 2004;126:78S–92S.

70. 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.

71. Stupi AM, Steen VD, Owens GR, et al. Pulmonary hypertension in

the CREST syndrome variant of systemic sclerosis. Arthritis Rheum.

1986;29:515–24.

72. Kuhn KP, Byrne DW, Arbogast PG, et al. Outcome in 91 consecutive

patients with pulmonary arterial hypertension receiving epoprostenol.

Am J Respir Crit Care Med. 2003;167:580–6.

73. Williams MH, Das C, Handler CE, et al. Systemic sclerosis

associated pulmonary hypertension: improved survival in the current

era. Heart. 2006;92:926 –32.

74. Petitpretz P, Brenot F, Azarian R, et al. Pulmonary hypertension in

patients with human immunodeficiency virus infection. Comparison

with primary pulmonary hypertension. Circulation. 1994;89:2722–7.

75. Hopkins WE, Ochoa LL, Richardson GW, et al. Comparison of the

hemodynamics and survival of adults with severe primary pulmonary

hypertension or Eisenmenger syndrome. J Heart Lung Transplant.

1996;15:100 –5.

76. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous

intravenous epoprostenol (prostacyclin) with conventional therapy for

primary pulmonary hypertension. The Primary Pulmonary Hypertension

Study Group. N Engl J Med. 1996;334:296 –302.

77. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary

hypertension: the impact of epoprostenol therapy. Circulation.

2002;106:1477– 82.

78. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous

epoprostenol infusion in primary pulmonary hypertension: prognostic

factors and survival. J Am Coll Cardiol. 2002;40:780–8.

79. Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for

pulmonary hypertension with associated congenital heart defects.

Circulation. 1999;99:1858–65.

80. Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous

epoprostenol for pulmonary hypertension due to the scleroderma

spectrum of disease. A randomized, controlled trial. Ann

Intern Med. 2000;132:425–34.

81. Barst RJ, Galie N, Naeije R, et al. Long-term outcome in pulmonary

arterial hypertension patients treated with subcutaneous treprostinil.

Eur Respir J. 2006;28:1195–203.

82. McLaughlin VV, Sitbon O, Badesch DB, et al. Survival with

first-line bosentan in patients with primary pulmonary hypertension.

Eur Respir J. 2005;25:244 –9.

83. 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;327:76–81.

84. Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium

channel blockers in idiopathic pulmonary arterial hypertension.

Circulation. 2005;111:3105–11.

85. Frank H, Mlczoch J, Huber K, et al. The effect of anticoagulant

therapy in primary and anorectic drug-induced pulmonary hypertension.

Chest. 1997;112:714 –21.

86. Miyamoto S, Nagaya N, Satoh T, et al. Clinical correlates and

prognostic significance of six-minute walk test in patients with

primary pulmonary hypertension. Comparison with cardiopulmonary

exercise testing. Am J Respir Crit Care Med. 2000;161:487–92.

87. Wensel R, Opitz CF, Anker SD, et al. Assessment of survival in

patients with primary pulmonary hypertension: importance of cardiopulmonary

exercise testing. Circulation. 2002;106:319 –24.

88. Gomberg-Maitland M, Huo D, Benza RL, et al. Creation of a model

comparing 6-minute walk test to metabolic equivalent in evaluating

treatment effects in pulmonary arterial hypertension. J Heart Lung

Transplant. 2007;26:732– 8.

89. Sandoval J, Bauerle O, Palomar A, et al. Survival in primary

pulmonary hypertension. Validation of a prognostic equation. Circulation.

1994;89:1733– 44.

90. Eysmann SB, Palevsky HI, Reichek N, et al. Two-dimensional and

Doppler-echocardiographic and cardiac catheterization correlates of

survival in primary pulmonary hypertension. Circulation. 1989;80:

353–60.

91. Tei C, Dujardin KS, Hodge DO, et al. Doppler echocardiographic

index for assessment of global right ventricular function. J Am Soc

Echocardiogr. 1996;9:838–47.

92. Yeo TC, Dujardin KS, Tei C, et al. Value of a Doppler-derived index

combining systolic and diastolic time intervals in predicting outcome in

primary pulmonary hypertension. Am J Cardiol. 1998;81:1157–61.

93. van Wolferen SA, Marcus JT, Boonstra A, et al. Prognostic value of

right ventricular mass, volume, and function in idiopathic pulmonary

arterial hypertension. Eur Heart J. 2007;28:1250 –7.

94. Gan CT, Lankhaar JW, Westerhof N, et al. Noninvasively assessed

pulmonary artery stiffness predicts mortality in pulmonary arterial

hypertension. Chest. 2007;132:1906 –12.

95. Fijalkowska A, Kurzyna M, Torbicki A, et al. Serum N-terminal

brain natriuretic peptide as a prognostic parameter in patients with

pulmonary hypertension. Chest. 2006;129:1313–21.

96. Nagaya N, Nishikimi T, Uematsu M, et al. Plasma brain natriuretic

peptide as a prognostic indicator in patients with primary pulmonary

hypertension. Circulation. 2000;102:865–70.

97. Nagaya N, Uematsu M, Satoh T, et al. Serum uric acid levels

correlate with the severity and the mortality of primary pulmonary

hypertension. Am J Respir Crit Care Med. 1999;160:487–92.

98. Torbicki A, Kurzyna M, Kuca P, et al. Detectable serum cardiac

troponin T as a marker of poor prognosis among patients with

chronic precapillary pulmonary hypertension. Circulation. 2003;108:

844–8.

99. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension.

Circulation. 2006;114:1417–31.

100. McGoon M, Fuster V, Freeman W, Edwards W, Scott J. Pulmonary

hypertension. In: Giuliani E, Gersh B, McGoon M, et al., editors.

Mayo Clinic practice of cardiology. St. Louis, MO: Mosby, 1996:

1815–36.

101. Currie PJ, Seward JB, Chan KL, et al. Continuous wave Doppler

determination of right ventricular pressure: a simultaneous Dopplercatheterization

study in 127 patients. J Am Coll Cardiol. 1985;6:

750–6.

102. Hinderliter AL, Willis PW, Long WA, et al. Frequency and severity of

tricuspid regurgitation determined by Doppler echocardiography in

primary pulmonary hypertension. Am J Cardiol. 2003;91:1033–7, A9.

102a.Lantheus Medical Imaging. Definity prescribing information. 2008.

Available at: http://www.definityimaging.com/prescribing_info.html.

Accessed February 11, 2009.

103. Pengo V, Lensing AW, Prins MH, et al. Incidence of chronic

thromboembolic pulmonary hypertension after pulmonary embolism.

N Engl J Med. 2004;350:2257– 64.

104. Hoeper MM, Mayer E, Simonneau G, et al. Chronic thromboembolic

pulmonary hypertension. Circulation. 2006;113:2011–20.

105. Galie N, Torbicki A, Barst R, et al. Guidelines on diagnosis and

treatment of pulmonary arterial hypertension. The Task Force on

Diagnosis and Treatment of Pulmonary Arterial Hypertension of the

European Society of Cardiology. Eur Heart J. 2004;25:2243–78.

106. Rubin LJ. Diagnosis and management of pulmonary arterial hypertension:

ACCP evidence-based clinical practice guidelines. Chest.

2004;126:7S–10S.

107. Hoeper MM, Maier R, Tongers J, et al. Determination of cardiac

output by the Fick method, thermodilution, and acetylene rebreathing

in pulmonary hypertension. Am J Respir Crit Care Med.

1999;160:535– 41.

108. Hoeper MM, Lee SH, Voswinckel R, et al. Complications of right

heart catheterization procedures in patients with pulmonary hypertension

in experienced centers. J Am Coll Cardiol. 2006;48:2546 –52.

109. Fruhwald FM, Kjellstrom B, Perthold W, et al. Hemodynamic

observations in two pulmonary hypertensive patients changing treatment

from inhaled iloprost to the oral endothelin-antagonist bosentan.

J Heart Lung Transplant. 2005;24:631– 4.

110. Wonisch M, Fruhwald FM, Maier R, et al. Continuous haemodynamic

monitoring during exercise in patients with pulmonary hypertension.

Int J Cardiol. 2005;101:415–20.

111. Karamanoglu M, McGoon M, Frantz RP, et al. Right ventricular

pressure waveform and wave reflection analysis in patients with

pulmonary arterial hypertension. Chest. 2007;132:37– 43.

112. Morales-Blanhir J, Santos S, de Jover L, et al. Clinical value of

vasodilator test with inhaled nitric oxide for predicting long-term

response to oral vasodilators in pulmonary hypertension. Respir Med.

2004;98:225–34.

113. Pepke-Zaba J, Higenbottam TW, Dinh’Xuan AT, et al. Inhaled

nitric oxide as a cause of selective pulmonary vasodilatation in

pulmonary hypertension. Lancet. 1991;338:1173– 4.

114. Rubin LJ, Groves BM, Reeves JT, et al. Prostacyclin-induced acute

pulmonary vasodilation in primary pulmonary hypertension. Circulation.

1982;66:334–8.

115. Schrader BJ, Inbar S, Kaufmann L, et al. Comparison of the effects

of adenosine and nifedipine in pulmonary hypertension. J Am Coll

Cardiol. 1992;19:1060–4.

116. Weir EK, Rubin LJ, Ayres SM, et al. The acute administration of

vasodilators in primary pulmonary hypertension. Experience from the

National Institutes of Health Registry on Primary Pulmonary Hypertension.

Am Rev Respir Dis. 1989;140:1623–30.

117. Badesch DB, Abman SH, Simonneau G, et al. Medical therapy for

pulmonary arterial hypertension: updated ACCP evidence-based

clinical practice guidelines. Chest. 2007;131:1917–28.

118. Elliott CG, Glissmeyer EW, Havlena GT, et al. Relationship of

BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension.

Circulation. 2006;113:2509 –15.

119. Simonneau G, Fartoukh M, Sitbon O, et al. Primary pulmonary

hypertension associated with the use of fenfluramine derivatives.

Chest. 1998;114:195S–9S.

120. Klings ES, Hill NS, Ieong MH, et al. Systemic sclerosis-associated

pulmonary hypertension: short- and long-term effects of epoprostenol

(prostacyclin). Arthritis Rheum. 1999;42:2638–45.

121. Bocchi EA, Bacal F, Auler Junior JO, et al. Inhaled nitric oxide

leading to pulmonary edema in stable severe heart failure. Am J

Cardiol. 1994;74:70 –2.

122. Galie N, Seeger W, Naeije R, et al. Comparative analysis of clinical

trials and evidence-based treatment algorithm in pulmonary arterial

hypertension. J Am Coll Cardiol. 2004;43:81S– 8S.

123. Mereles D, Ehlken N, Kreuscher S, et al. Exercise and respiratory

training improve exercise capacity and quality of life in patients with

severe chronic pulmonary hypertension. Circulation. 2006;114:

1482–9.

124. Mohr LC. Hypoxia during air travel in adults with pulmonary

disease. Am J Med Sci. 2008;335:71–9.

125. Weiss BM, Zemp L, Seifert B, et al. Outcome of pulmonary vascular

disease in pregnancy: a systematic overview from 1978 through 1996.

J Am Coll Cardiol. 1998;31:1650 –7.

126. Fuster V, Steele PM, Edwards WD, et al. Primary pulmonary

hypertension: natural history and the importance of thrombosis.

Circulation. 1984;70:580 –7.

127. Rich S, Seidlitz M, Dodin E, et al. The short-term effects of digoxin

in patients with right ventricular dysfunction from pulmonary hypertension.

Chest. 1998;114:787–92.

128. Aguilar RV, Farber HW. Epoprostenol (prostacyclin) therapy in

HIV-associated pulmonary hypertension. Am J Respir Crit Care

Med. 2000;162:1846 –50.

129. Kuo PC, Johnson LB, Plotkin JS, et al. Continuous intravenous

infusion of epoprostenol for the treatment of portopulmonary hypertension.

Transplantation. 1997;63:604–6.

130. McLaughlin VV, Genthner DE, Panella MM, et al. Compassionate

use of continuous prostacyclin in the management of secondary

pulmonary hypertension: a case series. Ann Intern Med. 1999;130:

740–3.

131. Nunes H, Humbert M, Sitbon O, et al. Prognostic factors for survival

in human immunodeficiency virus-associated pulmonary arterial hypertension.

Am J Respir Crit Care Med. 2003;167:1433–9.

132. Rich S, McLaughlin VV. The effects of chronic prostacyclin therapy

on cardiac output and symptoms in primary pulmonary hypertension.

J Am Coll Cardiol. 1999;34:1184 –7.

133. Laliberte K, Arneson C, Jeffs R, et al. Pharmacokinetics and

steady-state bioequivalence of treprostinil sodium (Remodulin) administered

by the intravenous and subcutaneous route to normal

volunteers. J Cardiovasc Pharmacol. 2004;44:209 –14.

134. Simonneau G, Barst RJ, Galie N, 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:

800–4.

135. Tapson VF, Gomberg-Maitland M, McLaughlin VV, et al. Safety

and efficacy of IV treprostinil for pulmonary arterial hypertension: a

prospective, multicenter, open-label, 12–week trial. Chest. 2006;129:

683–8.

136. Gomberg-Maitland M, Tapson VF, Benza RL, et al. Transition

from intravenous epoprostenol to intravenous treprostinil in pulmonary

hypertension. Am J Respir Crit Care Med. 2005;172:1586 –9.

137. Centers for Disease Control and Prevention. Bloodstream infections

among patients treated with intravenous epoprostenol or intravenous

treprostinil for pulmonary arterial hypertension—seven sites, United

States, 2003–2006. MMWR Morb Mortal Wkly Rep. 2007;56:

170–2.

138. Doran A, Ivy D, Barst RJ, et al. Guidelines for the prevention of

central venous catheter-related bloodstream infections with prostanoid

therapy for pulmonary arterial hypertension. Adv Pulm Hypertens.

2008; 7:245–248.

139. Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for

severe pulmonary hypertension. N Engl J Med. 2002;347:322–9.

140. Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment

of primary pulmonary hypertension with aerosolized iloprost, a

prostacyclin analogue. N Engl J Med. 2000;342:1866 –70.

141. Opitz CF, Wensel R, Winkler J, et al. Clinical efficacy and survival

with first-line inhaled iloprost therapy in patients with idiopathic

pulmonary arterial hypertension. Eur Heart J. 2005;26:1895–902.

142. Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual

endothelin-receptor antagonist bosentan in patients with pulmonary

hypertension: a randomised placebo-controlled study. Lancet. 2001;

358:1119 –23.

143. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for

pulmonary arterial hypertension. N Engl J Med. 2002;346:896 –903.

144. Provencher S, Sitbon O, Humbert M, et al. Long-term outcome with

first-line bosentan therapy in idiopathic pulmonary arterial hypertension.

Eur Heart J. 2006;27:589 –95.

145. Sitbon O, McLaughlin VV, Badesch DB, et al. Survival in patients

with class III idiopathic pulmonary arterial hypertension treated with

first line oral bosentan compared with an historical cohort of patients

started on intravenous epoprostenol. Thorax. 2005;60:1025–30.

146. Galie N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in

patients with Eisenmenger syndrome: a multicenter, double-blind,

randomized, placebo-controlled study. Circulation. 2006;114:48 –54.

147. Jais X, D’Armini AM, Jansa P, 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;52:2127–34.

148. Sitbon O, Gressin V, Speich R, et al. Bosentan for the treatment of

human immunodeficiency virus-associated pulmonary arterial hypertension.

Am J Respir Crit Care Med. 2004;170:1212–7.

149. Galie N, Rubin L, Hoeper M, et al. Treatment of patients with

mildly symptomatic pulmonary arterial hypertension with bosentan

(EARLY study): a double-blind, randomised controlled trial. Lancet.

2008;371:2093–100.

150. Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for

pulmonary arterial hypertension. Am J Respir Crit Care Med.

2004;169:441–7.

151. Barst RJ, Rich S, Widlitz A, et al. Clinical efficacy of sitaxsentan, an

endothelin-A receptor antagonist, in patients with pulmonary arterial

hypertension: open-label pilot study. Chest. 2002;121:1860–8.

152. Galie N, Badesch D, Oudiz R, et al. Ambrisentan therapy for pulmonary

arterial hypertension. J Am Coll Cardiol. 2005;46:529–35.

153. Galie N, Olschewski H, Oudiz RJ, 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 (abstr). Circulation. 2008;117:3010 –9.

154. Gilead. Letairis full prescribing information. 2008. Available at:

http://www.letairis.com/full_prescribing_information.html. Accessed

February 11, 2009.

155. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for

pulmonary arterial hypertension. N Engl J Med. 2005;353:2148–57.

156. Hoeper MM, Welte T. Sildenafil citrate therapy for pulmonary

arterial hypertension. N Engl J Med. 2006;354:1091–3.

157. Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan

with epoprostenol in pulmonary arterial hypertension: BREATHE-2.

Eur Respir J. 2004;24:353–9.

158. McLaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of

adding inhaled iloprost to existing bosentan in pulmonary arterial

hypertension. Am J Respir Crit Care Med. 2006;174:1257– 63.

159. Hoeper MM, Leuchte H, Halank M, et al. Combining inhaled

iloprost with bosentan in patients with idiopathic pulmonary arterial

hypertension. Eur Respir J. 2006;28:691– 4.

160. Simonneau G, Rubin LJ, Galie N, et al. Addition of sildenafil to

long-term intravenous epoprostenol therapy in patients with pulmonary

arterial hypertension: a randomized trial. Ann Intern Med.

2008;149:521–30.

161. Macchia A, Marchioli R, Marfisi R, et al. A meta-analysis of trials of

pulmonary hypertension: a clinical condition looking for drugs and

research methodology. Am Heart J. 2007;153:1037– 47.

161a.Galie N, Manes A, Negro L, et al. A meta-analysis of randomized

controlled trials in pulmonary arterial hypertension. Eur Heart J.

2009;30:394– 403.

162. Avouac J, Wipff J, Kahan A, et al. Effects of oral treatments on

exercise capacity in systemic sclerosis related pulmonary arterial

hypertension: a meta-analysis of randomised controlled trials. Ann

Rheum Dis. 2008;67:808 –14.

163. Ambrisentan (Letairis) for pulmonary arterial hypertension. Med

Lett Drugs Ther. 2007;49:87– 8.

164. Doyle RL, McCrory D, Channick RN, et al. Surgical treatments/

interventions for pulmonary arterial hypertension: ACCP evidencebased

clinical practice guidelines. Chest. 2004;126:63S–71S.

165. Klepetko W, Mayer E, Sandoval J, et al. Interventional and surgical

modalities of treatment for pulmonary arterial hypertension. J Am

Coll Cardiol. 2004;43:73S– 80S.

166. Olsson JK, Zamanian RT, Feinstein JA, et al. Surgical and interventional

therapies for pulmonary arterial hypertension. Semin Respir

Crit Care Med. 2005;26:417–28.

167. Reichenberger F, Pepke-Zaba J, McNeil K, et al. Atrial septostomy

in the treatment of severe pulmonary arterial hypertension. Thorax.

2003;58:797– 800.

168. Rothman A, Sklansky MS, Lucas VW, et al. Atrial septostomy as a

bridge to lung transplantation in patients with severe pulmonary

hypertension. Am J Cardiol. 1999;84:682– 6.

169. Sandoval J, Gaspar J, Pulido T, et al. Graded balloon dilation atrial

septostomy in severe primary pulmonary hypertension. A therapeutic

alternative for patients nonresponsive to vasodilator treatment. J Am

Coll Cardiol. 1998;32:297–304.

170. O’Loughlin AJ, Keogh A, Muller DW. Insertion of a fenestrated

Amplatzer atrial septostomy device for severe pulmonary hypertension.

Heart Lung Circ. 2006;15:275–7.

171. Moscucci M, Dairywala IT, Chetcuti S, et al. Balloon atrial septostomy

in end-stage pulmonary hypertension guided by a novel

intracardiac echocardiographic transducer. Catheter Cardiovasc Interv.

2001;52:530–4.

172. Trulock EP, Edwards LB, Taylor DO, et al. Registry of the

International Society for Heart and Lung Transplantation: twentythird

official adult lung and heart-lung transplantation report—2006.

J Heart Lung Transplant. 2006;25:880 –92.

173. Deleted in proof.

174. Cottini SR, Lerch N, de Perrot M, et al. Risk factors for reperfusion

injury after lung transplantation. Intensive Care Med. 2006;32:557–63.

175. Choong CK, Sweet SC, Guthrie TJ, et al. Repair of congenital heart

lesions combined with lung transplantation for the treatment of

severe pulmonary hypertension: a 13–year experience. J Thorac

Cardiovasc Surg. 2005;129:661–9.

176. Kindo M, Radovancevic B, Gregoric ID, et al. Biventricular support

with the Jarvik 2000 ventricular assist device in a calf model of

pulmonary hypertension. ASAIO J. 2004;50:444 –50.

177. Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348:

2007–18.

178. 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.

179. Sablotzki A, Czeslick E, Gruenig E, et al. First experiences with the

stable prostacyclin analog iloprost in the evaluation of heart transplant

candidates with increased pulmonary vascular resistance. J Thorac

Cardiovasc Surg. 2003;125:960 –2.

180. Konstam MA, DeNofrio D. Endothelin expression and the progression

of heart failure: exemplifying the vagaries of therapeutic development.

Circulation. 2004;109:143–5.

181. Sutsch G, Kiowski W, Yan XW, et al. Short-term oral endothelinreceptor

antagonist therapy in conventionally treated patients with

symptomatic severe chronic heart failure. Circulation. 1998;98:

2262–8.

182. Mylona P, Cleland JG. Update of REACH-1 and MERIT-HF

clinical trials in heart failure. Cardio.net Editorial Team. Eur J Heart

Fail. 1999;1:197–200.

183. Teerlink JR. Recent heart failure trials of neurohormonal modulation

(OVERTURE and ENABLE): approaching the asymptote of efficacy?

J Card Fail. 2002;8:124 –7.

184. Perez-Villa F, Cuppoletti A, Rossel V, et al. Initial experience with

bosentan therapy in patients considered ineligible for heart transplantation

because of severe pulmonary hypertension. Clin Transplant.

2006;20:239–44.

185. Brauchlin AE, Soccal PM, Rochat T, et al. Severe left ventricular

dysfunction secondary to primary pulmonary hypertension: bridging

therapy with bosentan before lung transplantation. J Heart Lung

Transplant. 2005;24:777– 80.

186. Alaeddini J, Uber PA, Park MH, et al. Efficacy and safety of sildenafil

in the evaluation of pulmonary hypertension in severe heart failure.

Am J Cardiol. 2004;94:1475–7.

187. Lepore JJ, Maroo A, Bigatello LM, et al. Hemodynamic effects of

sildenafil in patients with congestive heart failure and pulmonary

hypertension: combined administration with inhaled nitric oxide.

Chest. 2005;127:1647–53.

188. Lewis GD, Lachmann J, Camuso J, et al. Sildenafil improves exercise

hemodynamics and oxygen uptake in patients with systolic heart

failure. Circulation. 2007;115:59–66.

189. 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.

190. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure—

abnormalities in active relaxation and passive stiffness of the left

ventricle. N Engl J Med. 2004;350:1953–9.

191. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in

patients with chronic heart failure and preserved left-ventricular

ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:

777–81.

192. Rosenhek R, Rader F, Klaar U, et al. Outcome of watchful waiting in

asymptomatic severe mitral regurgitation. Circulation. 2006;113:

2238–44.

193. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006

guidelines for the management of patients with valvular heart disease:

a report of the American College of Cardiology/American Heart

Association Task Force on Practice Guidelines (Writing Committee

to Revise the 1998 Guidelines for the Management of Patients With

Valvular Heart Disease): developed in collaboration with the Society

of Cardiovascular Anesthesiologists: endorsed by the Society for

Cardiovascular Angiography and Interventions and the Society of

Thoracic Surgeons. J Am Coll Cardiol. 2006;48:e1–149.

194. Han MK, McLaughlin VV, Criner GJ, et al. Pulmonary diseases and

the heart. Circulation. 2007;116:2992–3005.

195. Higenbottam T. Pulmonary hypertension and chronic obstructive

pulmonary disease: a case for treatment. Proc Am Thorac Soc.

2005;2:12–9.

196. Naeije R. Pulmonary hypertension and right heart failure in chronic

obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2:20 –2.

197. Scharf SM, Iqbal M, Keller C, et al. Hemodynamic characterization

of patients with severe emphysema. Am J Respir Crit Care Med.

2002;166:314 –22.

198. Chaouat A, Bugnet AS, Kadaoui N, et al. Severe pulmonary

hypertension and chronic obstructive pulmonary disease. Am J Respir

Crit Care Med. 2005;172:189 –94.

199. Thabut G, Dauriat G, Stern JB, et al. Pulmonary hemodynamics in

advanced COPD candidates for lung volume reduction surgery or

lung transplantation. Chest. 2005;127:1531– 6.

200. Eddahibi S, Chaouat A, Morrell N, et al. Polymorphism of the

serotonin transporter gene and pulmonary hypertension in chronic

obstructive pulmonary disease. Circulation. 2003;108:1839–44.

201. Alp S, Skrygan M, Schmidt WE, et al. Sildenafil improves hemodynamic

parameters in COPD—an investigation of six patients.

Pulm Pharmacol Ther. 2006;19:386 –90.

202. Madden BP, Allenby M, Loke TK, et al. A potential role for

sildenafil in the management of pulmonary hypertension in patients

with parenchymal lung disease. Vascul Pharmacol. 2006;44:372– 6.

203. Maloney JP. Advances in the treatment of secondary pulmonary

hypertension. Curr Opin Pulm Med. 2003;9:139–43.

204. Ryu JH, Krowka MJ, Pellikka PA, et al. Pulmonary hypertension in

patients with interstitial lung diseases. Mayo Clin Proc. 2007;82:

342–50.

205. Nathan SD, Shlobin OA, Ahmad S, et al. Pulmonary hypertension

and pulmonary function testing in idiopathic pulmonary fibrosis.

Chest. 2007;131:657– 63.

206. Arcasoy SM, Christie JD, Ferrari VA, et al. Echocardiographic

assessment of pulmonary hypertension in patients with advanced lung

disease. Am J Respir Crit Care Med. 2003;167:735– 40.

207. Leuchte HH, Neurohr C, Baumgartner R, et al. Brain natriuretic

peptide and exercise capacity in lung fibrosis and pulmonary hypertension.

Am J Respir Crit Care Med. 2004;170:360 –5.

208. Shorr AF, Helman DL, Davies DB, et al. Pulmonary hypertension in

advanced sarcoidosis: epidemiology and clinical characteristics. Eur

Respir J. 2005;25:783– 8.

209. Fisher KA, Serlin DM, Wilson KC, et al. Sarcoidosis-associated

pulmonary hypertension: outcome with long-term epoprostenol

treatment. Chest. 2006;130:1481– 8.

210. Atwood CW Jr., McCrory D, Garcia JG, et al. Pulmonary artery

hypertension and sleep-disordered breathing: ACCP evidence-based

clinical practice guidelines. Chest. 2004;126:72S–7S.

211. Moser KM, Bloor CM. Pulmonary vascular lesions occurring in

patients with chronic major vessel thromboembolic pulmonary hypertension.

Chest. 1993;103:685–92.

212. Bonderman D, Jakowitsch J, Adlbrecht C, et al. Medical conditions

increasing the risk of chronic thromboembolic pulmonary hypertension.

Thromb Haemost. 2005;93:512– 6.

213. Jamieson SW, Kapelanski DP, Sakakibara N, et al. Pulmonary

endarterectomy: experience and lessons learned in 1,500 cases. Ann

Thorac Surg. 2003;76:1457– 62.

214. Kim NH. Assessment of operability in chronic thromboembolic

pulmonary hypertension. Proc Am Thorac Soc. 2006;3:584–8.

215. Feinstein JA, Goldhaber SZ, Lock JE, et al. Balloon pulmonary

angioplasty for treatment of chronic thromboembolic pulmonary

hypertension. Circulation. 2001;103:10 –3.

216. Bresser P, Pepke-Zaba J, Jais X, et al. Medical therapies for chronic

thromboembolic pulmonary hypertension: an evolving treatment

paradigm. Proc Am Thorac Soc. 2006;3:594–600.

217. Kerr KM, Rubin LJ. Epoprostenol therapy as a bridge to pulmonary

thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

Chest. 2003;123:319 –20.

218. Malouf JF, Enriquez-Sarano M, Pellikka PA, et al. Severe pulmonary

hypertension in patients with severe aortic valve stenosis: clinical

profile and prognostic implications. J Am Coll Cardiol. 2002;40:

789–95.

219. Vincens JJ, Temizer D, Post JR, et al. Long-term outcome of cardiac

surgery in patients with mitral stenosis and severe pulmonary hypertension.

Circulation. 1995;92:II137– 42.

220. Yang H, Davidson WR Jr., Chambers CE, et al. Preoperative

pulmonary hypertension is associated with postoperative left ventricular

dysfunction in chronic organic mitral regurgitation: an echocardiographic

and hemodynamic study. J Am Soc Echocardiogr. 2006;

19:1051–5.

221. Costard-Jackle A, Fowler MB. Influence of preoperative pulmonary

artery pressure on mortality after heart transplantation: testing of

potential reversibility of pulmonary hypertension with nitroprusside is

useful in defining a high risk group. J Am Coll Cardiol. 1992;19:48–54.

222. Aris A, Camara ML. As originally published in 1988: long-term

results of mitral valve surgery in patients with severe pulmonary

hypertension. Updated in 1996. Ann Thorac Surg. 1996;61:1583– 4.

223. Umesan CV, Kapoor A, Sinha N, et al. Effect of Inoue balloon mitral

valvotomy on severe pulmonary arterial hypertension in 315 patients

with rheumatic mitral stenosis: immediate and long-term results.

J Heart Valve Dis. 2000;9:609 –15.

224. Argenziano M, Choudhri AF, Moazami N, et al. Randomized,

double-blind trial of inhaled nitric oxide in LVAD recipients with

pulmonary hypertension. Ann Thorac Surg. 1998;65:340 –5.

225. Chang PP, Longenecker JC, Wang NY, et al. Mild vs severe

pulmonary hypertension before heart transplantation: different effects

on posttransplantation pulmonary hypertension and mortality.

J Heart Lung Transplant. 2005;24:998 –1007.

226. Beck JR, Mongero LB, Kroslowitz RM, et al. Inhaled nitric oxide

improves hemodynamics in patients with acute pulmonary hypertension

after high-risk cardiac surgery. Perfusion. 1999;14:37– 42.

227. Santini F, Casali G, Franchi G, et al. Hemodynamic effects of

inhaled nitric oxide and phosphodiesterase inhibitor (dipyridamole)

on secondary pulmonary hypertension following heart valve surgery in

adults. Int J Cardiol. 2005;103:156–63.

228. Rea RS, Ansani NT, Seybert AL. Role of inhaled nitric oxide in adult

heart or lung transplant recipients. Ann Pharmacother. 2005;39:913–7.

229. Lowson SM, Doctor A, Walsh BK, et al. Inhaled prostacyclin for the

treatment of pulmonary hypertension after cardiac surgery. Crit Care

Med. 2002;30:2762– 4.

230. Fattouch K, Sbraga F, Bianco G, et al. Inhaled prostacyclin, nitric

oxide, and nitroprusside in pulmonary hypertension after mitral valve

replacement. J Card Surg. 2005;20:171– 6.

231. Theodoraki K, Tsiapras D, Tsourelis L, et al. Inhaled iloprost in

eight heart transplant recipients presenting with post-bypass acute

right ventricular dysfunction. Acta Anaesthesiol Scand. 2006;50:

1213–7.

232. Madden BP, Sheth A, Ho TB, et al. Potential role for sildenafil in

the management of perioperative pulmonary hypertension and right

ventricular dysfunction after cardiac surgery. Br J Anaesth. 2004;93:

155–6.

233. Trachte AL, Lobato EB, Urdaneta F, et al. Oral sildenafil reduces

pulmonary hypertension after cardiac surgery. Ann Thorac Surg.

2005;79:194 –7.

234. Carteaux JP, Roux S, Siaghy M, et al. Acute pulmonary hypertension

after cardiopulmonary bypass in pig: the role of endogenous endothelin.

Eur J Cardiothorac Surg. 1999;15:346 –52.

235. Friedman WF. Proceedings of National Heart, Lung, and Blood

Institute pediatric cardiology workshop: pulmonary hypertension.

Pediatr Res. 1986;20:811–24.

236. Roberts KE, McElroy JJ, Wong WP, et al. BMPR2 mutations in

pulmonary arterial hypertension with congenital heart disease. Eur

Respir J. 2004;24:371– 4.

237. Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary

pulmonary hypertension in children. Circulation. 1999;99:1197–208.

238. Yung D, Widlitz AC, Rosenzweig EB, et al. Outcomes in children

with idiopathic pulmonary arterial hypertension. Circulation. 2004;

110:660 –5.

239. Rosenzweig EB, Ivy DD, Widlitz A, et al. Effects of long-term

bosentan in children with pulmonary arterial hypertension. J Am Coll

Cardiol. 2005;46:697–704.