Abstract
Pulmonary hypertension is a common complication of connective tissue disease (CTD) and confers a worse prognosis. Connective tissue disease associated pulmonary hypertension (CTD-PH) occurs most often with systemic sclerosis (SSc) but may also complicate mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), and, rarely, rheumatoid arthritis, dermatomysositis/polymyositis, and Sjogren’s syndrome. Although the pathogenesis leading to CTD-PH may vary, the clinical presentation, treatment, and pathological lesions are often similar to those observed in idiopathic pulmonary arterial hypertension (IPAH). This chapter examines the epidemiology, pathophysiology, clinical presentation, and diagnosis of CTD-PH and the evidence supporting the available treatment options.
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References
Simonneau G, Galie N, Rubin LJ, Langleben D, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004;43:5S–12S.
Young RH, Mark GJ. Pulmonary vascular changes in scleroderma. Am J Med 1978; 64(6):998–1004.
Cool CD, Kennedy D, Voelkel NF, Tuder RM. Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection. Hum Pathol 1997; 28(4):434–42.
Saito A, Takizawa H, Ito K, Yamamoto K, et al. A case of pulmonary veno-occlusive disease associated with systemic sclerosis. Respirology 2003; 8(3):383–5.
Gugnani MK, Pierson C, Vanderheide R, Girgis RE. Pulmonary edema complicating prostacyclin therapy in pulmonary hypertension associated with scleroderma: A case of pulmonary capillary hemangiomatosis. Arthritis Rheum 2000; 43(3):699–703.
Morassut PA, Walley VM, Smith CD. Pulmonary veno-occlusive disease and the CREST variant of scleroderma. Can J Cardiol 1992; 8(10):1055–8.
Fagan KA, Badesch DB. Pulmonary hypertension associated with connective tissue disease. Prog Cardiovasc Dis 2002; 45(3):225–34.
Ungerer RG, Tashkin DP, Furst D, Clements PJ, et al. Prevalence and clinical correlates of pulmonary arterial hypertension in progressive systemic sclerosis. Am J Med 1983; 75(1):65–74.
Mukerjee D, St George D, Coleiro B, Knight C, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: Application of a registry approach. Ann Rheum Dis 2003; 62(11):1088–93.
Battle RW, Davitt MA, Cooper SM, Buckley LM, et al. Prevalence of pulmonary hypertension in limited and diffuse scleroderma. Chest 1996; 110(6):1515–9.
Pope JE, Lee P, Baron M, Dunne J, et al. Prevalence of elevated pulmonary arterial pressures measured by echocardiography in a multicenter study of patients with systemic sclerosis. J Rheumatol 2005; 32(7):1273–8.
Koh ET, Lee P, Gladman DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: An analysis of 17 patients. Br J Rheumatol 1996; 35(10): 989–93.
Schachna L, Wigley FM, Chang B, White B, et al. Age and risk of pulmonary arterial hypertension in scleroderma. Chest 2003; 124(6): 2098–104.
Yousem SA. The pulmonary pathologic manifestations of the CREST syndrome. Hum Pathol 1990; 21(5):467–74.
al Sabbagh MR, Steen VD, Zee BC, Nalesnik M, et al. Pulmonary arterial histology and morphometry in systemic sclerosis: A case-control autopsy study. J Rheumatol 1989; 16(8):1038–42.
Steen V, Medsger TA, Jr. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum 2003; 48(2):516–22.
Stupi AM, Steen VD, Owens GR, Barnes EL, et al. Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis. Arthritis Rheum 1986; 29(4):515–24.
Lee P, Langevitz P, Alderdice CA, Aubrey M, et al. Mortality in systemic sclerosis (scleroderma). Quar J Med 1992; 82(298):139–48.
Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI. et al. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003; 123(2):344–50.
Bull TM, Fagan KA, Badesch DB. Pulmonary vascular manifestations of mixed connective tissue disease. Rheum Dis Clin North Am 2005; 31(3):451–64, vi.
Hosoda Y, Suzuki Y, Takano M, Tojo T, et al. Mixed connective tissue disease with pulmonary hypertension: A clinical and pathological study. J Rheum 1987; 14(4):826–30.
Esther JH, Sharp GC, Agia GA. Pulmonary hypertension in patients with connective tissue disease and anti-nuclear ribonucleoprotein. Arthritis Rheum 1981; 24:S105.
Sullivan WD, Hurst DJ, Harmon CE, Esther JH, et al. A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine (Baltimore) 1984; 63(2):92–107.
Burdt MA, Hoffman RW, Deutscher SL, Wang GS, et al. Long-term outcome in mixed connective tissue disease: Longitudinal clinical and serologic findings. Arthritis Rheum 1999; 42(5):899–909.
Asherson RA, Morgan SH, Hackett D, Montanes P, et al. Rheumatoid arthritis and pulmonary hypertension. A report of three cases. J Rheum 1985; 12(1):154–9.
Balagopal VP, da Costa P, Greenstone MA. Fatal pulmonary hypertension and rheumatoid vasculitis. Eur Respir J 1995; 8(2):331–3.
Morikawa J, Kitamura K, Habuchi Y, Tsujimura Y, et al. Pulmonary hypertension in a patient with rheumatoid arthritis. Chest 1988; 93(4):876–8.
Young ID, Ford SE, Ford PM. The association of pulmonary hypertension with rheumatoid arthritis. J Rheum 1989; 16(9):1266–9.
Kay JM, Banik S. Unexplained pulmonary hypertension with pulmonary arteritis in rheumatoid disease. Br J Dis Chest 1977; 71(1):53–9.
Dawson JK, Goodson NG, Graham DR, Lynch MP. Raised pulmonary artery pressures measured with Doppler echocardiography in rheumatoid arthritis patients. Rheumatology (Oxford) 2000; 39(12):1320–5.
Baydur A, Mongan ES, Slager UT. Acute respiratory failure and pulmonary arteritis without parenchymal involvement: Demonstration in a patient with rheumatoid arthritis. Chest 1979; 75(4):518–20.
Pan TL, Thumboo J, Boey ML. Primary and secondary pulmonary hypertension in systemic lupus erythematosus. Lupus 2000; 9(5):338–42.
Shen JY, Chen SL, Wu YX, Tao RQ, et al. Pulmonary hypertension in systemic lupus erythematosus. Rheum Int 1999; 18(4):147–51.
Li EK, Tam LS. Pulmonary hypertension in systemic lupus erythematosus: Clinical association and survival in 18 patients. J Rheum 1999; 26(9):1923–9.
Simonson JS, Schiller NB, Petri M, Hellmann DB. Pulmonary hypertension in systemic lupus erythematosus. J Rheum 1989; 16(7):918–25.
Falcao CA, Alves IC, Chahade WH, Duarte AL, et al. Echocardiographic abnormalities and antiphospholipid antibodies in patients with systemic lupus erythematosus. Arq Bras Cardiol 2002; 79(3):285–91.
Robbins IM, Gaine SP, Schilz R, Tapson VF, et al. Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus. Chest 2000; 117(1):14–8.
Fayemi AO. Pulmonary vascular disease in systemic lupus erythematosus. Am J Clin Pathol 1976; 65(3):284–90.
Schwartzberg M, Lieberman DH, Getzoff B, Ehrlich GE. Systemic lupus erythematosus and pulmonary vascular hypertension. Arch Intern Med 1984; 144(3):605–7.
Sack KE, Bekheit S, Fadem SZ, Bedrossian CW. Severe pulmonary vascular disease in systemic lupus erythematosus. South Med J 1979; 72(8):1016–8.
Nair SS, Askari AD, Popelka CG, Kleinerman JF. Pulmonary hypertension and systemic lupus erythematosus. Arch Intern Med 1980; 140(1):109–11.
Hoeper MM. Pulmonary hypertension in collagen vascular disease. Eur Respir J 2002; 19(3):571–6.
Du L, Sullivan CC, Chu D, Cho AJ, et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003; 348(6):500–9.
Kharitonov SA, Cailes JB, Black CM, Du Bois RM, et al. Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension. Thorax 1997; 52(12):1051–5.
Rolla G, Colagrande P, Scappaticci E, Chiavassa G, et al. Exhaled nitric oxide in systemic sclerosis: Relationships with lung involvement and pulmonary hypertension. J Rheum 2000; 27(7):1693–8.
Kawaguchi Y, Tochimoto A, Hara M, Kawamoto M, et al. NOS2 polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: Contribution to the transcriptional activity. Arthritis Res Ther 2006; 8(4):R104.
Morse J, Barst R, Horn E, Cuervo N, et al. Pulmonary hypertension in scleroderma spectrum of disease: Lack of bone morphogenetic protein receptor 2 mutations. J Rheum 2002; 29(11):2379–81.
Yamane K, Miyauchi T, Suzuki N, Yuhara T, et al. Significance of plasma endothelin-1 levels in patients with systemic sclerosis. J Rheum 1992; 19(10):1566–71.
Vancheeswaran R, Magoulas T, Efrat G, Wheeler-Jones C, et al. Circulating endothelin-1 levels in systemic sclerosis subsets—A marker of fibrosis or vascular dysfunction? J Rheum 1994; 21(10):1838–44.
Morelli S, Ferri C, Polettini E, Bellini C, et al. Plasma endothelin-1 levels, pulmonary hypertension, and lung fibrosis in patients with systemic sclerosis. Am J Med 1995; 99(3):255–60.
Julkunen H, Saijonmaa O, Gronhagen-Riska C, Teppo AM, et al. Raised plasma concentrations of endothelin-1 in systemic lupus erythematosus. Ann Rheum Dis 1991; 50(7):526–7.
Kawaguchi Y, Suzuki K, Hara M, Hidaka T, et al. Increased endothelin-1 production in fibroblasts derived from patients with systemic sclerosis. Ann Rheum Dis 1994; 53(8):506–10.
Odoux C, Crestani B, Lebrun G, Rolland C, et al. Endothelin-1 secretion by alveolar macrophages in systemic sclerosis. Am J Respir Crit Care Med 1997; 156(5):1429–35.
Abraham DJ, Vancheeswaran R, Dashwood MR, Rajkumar VS, et al. Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 1997; 151(3):831–41.
Hachulla E, Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: Endothelin receptor antagonism. Ann Rheum Dis 2004; 63(9):1009–14.
Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther 2003; 5(2):80–93.
Cepeda EJ, Reveille JD. Autoantibodies in systemic sclerosis and fibrosing syndromes: Clinical indications and relevance. Curr Opin Rheum 2004; 16(6):723–32.
Steen VD, Powell DL, Medsger TA, Jr. Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum 1988; 31(2):196–203.
Steen VD, Ziegler GL, Rodnan GP, Medsger TA, Jr. Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum 1984; 27(2):125–31.
Sacks DG, Okano Y, Steen VD, Curtiss E, et al. Isolated pulmonary hypertension in systemic sclerosis with diffuse cutaneous involvement: Association with serum anti-U3RNP antibody. J Rheum 1996; 23(4):639–42.
Ulanet DB, Wigley FM, Gelber AC, Rosen A. Autoantibodies against B23, a nucleolar phosphoprotein, occur in scleroderma and are associated with pulmonary hypertension. Arthritis Rheum 2003; 49(1):85–92.
Yoshio T, Masuyama J, Sumiya M, Minota S, et al. Antiendothelial cell antibodies and their relation to pulmonary hypertension in systemic lupus erythematosus. J Rheum 1994; 21(11):2058–63.
Negi VS, Tripathy NK, Misra R, Nityanand S. Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension. J Rheum 1998; 25(3):462–6.
Kuwana M, Kaburaki J, Okano Y, Tojo T, et al. Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum 1994; 37(1):75–83.
Okawa-Takatsuji M, Aotsuka S, Fujinami M, Uwatoko S, et al. Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein. Clin Exp Immunol 1999; 116(1):174–80.
Bordron A, Dueymes M, Levy Y, Jamin C, et al. The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis. J Clin Invest 1998; 101(10):2029–35.
Sgonc R, Gruschwitz MS, Dietrich H, Recheis H, et al. Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J Clin Invest 1996; 98(3):785–92.
Sakao S, Taraseviciene-Stewart L, Wood K, Cool CD, et al. Apoptosis of pulmonary microvascular endothelial cells stimulates vascular smooth muscle cell growth. Am J Physiol Lung Cell Mol Physiol 2006; 291(3):L362–L368.
Filep JG, Bodolay E, Sipka S, Gyimesi E, et al. Plasma endothelin correlates with antiendothelial antibodies in patients with mixed connective tissue disease. Circulation 1995; 92(10):2969–74.
Balasubramaniam V, Le Cras TD, Ivy DD, Grover TR, et al. Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 2003; 284(5):L826–L833.
Humbert M, Monti G, Fartoukh M, Magnan A, et al. Platelet-derived growth factor expression in primary pulmonary hypertension: Comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 1998; 11(3):554–9.
Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 2005; 115(10):2811–21.
Patterson KC, Weissmann A, Ahmadi T, Farber HW. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med 2006; 145(2):152–3.
Ghofrani HA, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 2005; 353(13):1412–3.
Baroni SS, Santillo M, Bevilacqua F, Luchetti M, et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 2006; 354(25):2667–76.
Barst RJ, McGoon M, Torbicki A, Sitbon O, et al. Diagnosis and Differential Assessment of Pulmonary Arterial Hypertension. J Am Coll Cardiol 2004; 43:40S–47S.
Owens GR, Fino GJ, Herbert DL, Steen VD, et al. Pulmonary function in progressive systemic sclerosis. Comparison of CREST syndrome variant with diffuse scleroderma. Chest 1983; 84(5):546–50.
Steen VD, Graham G, Conte C, Owens G, et al. Isolated diffusing capacity reduction in systemic sclerosis. Arthritis Rheum 1992; 35(7):765–70.
Denton CP, Cailes JB, Phillips GD, Wells AU, et al. Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Br J Rheum 1997; 36(2): 239–43.
Mukerjee D, St George D, Knight C, Davar J, et al. Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis. Rheumatology (Oxford) 2004; 43(4):461–6.
McGoon M, Gutterman D, Steen V, Barst R, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126(1 Suppl):14S–34S.
Nagaya N, Nishikimi T, Uematsu M, Satoh T, et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 2000; 102(8):865–70.
Allanore Y, Borderie D, Meune C, Cabanes L, et al. N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers. Arthritis Rheum 2003; 48(12):3503–8.
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.
Fuster V, Steele PM, Edwards WD, Gersh BJ, et al. Primary pulmonary hypertension: Natural history and the importance of thrombosis. Circulation 1984; 70(4):580–7.
Mariette X, Brenot F, Brouet JC. Recovery from pulmonary hypertension with steroid therapy in a patient with Sjogren’s syndrome and polymyositis. J Rheum 1994; 21(4):772–3.
Morelli S, Giordano M, De Marzio P, Priori R, et al. Pulmonary arterial hypertension responsive to immunosuppressive therapy in systemic lupus erythematosus. Lupus 1993; 2(6):367–9.
Lahaye IE, Rogiers PE, Nagler JM, Chappel R. Vanishing pulmonary hypertension in mixed connective tissue diseas. Clin Rheum 1999; 18(1):45–7.
Bellotto F, Chiavacci P, Laveder F, Angelini A, et al. Effective immunosuppressive therapy in a patient with primary pulmonary hypertension. Thorax 1999; 54(4):372–4.
Davas EM, Peppas C, Maragou M, Alvanou E, et al. Intravenous cyclophosphamide pulse therapy for the treatment of lung disease associated with scleroderma. Clin Rheum 1999; 18(6):455–61.
Karmochkine M, Wechsler B, Godeau P, Brenot F, et al. Improvement of severe pulmonary hypertension in a patient with SLE. Ann Rheum Dis 1996; 55(8):561–2.
Groen H, Bootsma H, Postma DS, Kallenberg CG. Primary pulmonary hypertension in a patient with systemic lupus erythematosus: Partial improvement with cyclophosphamide. J Rheum 1993; 20(6):1055–7.
Goupille P, Fauchier L, Babuty D, Fauchier JP, et al. Precapillary pulmonary hypertension dramatically improved with high doses of corticosteroids during systemic lupus erythematosus. J Rheum 1994; 21(10):1976–7.
Dahl M, Chalmers A, Wade J, Calverley D, et al. Ten year survival of a patient with advanced pulmonary hypertension and mixed connective tissue disease treated with immunosuppressive therapy. J Rheum 1992; 19(11):1807–9.
Ferri C, Emdin M, Storino FA, Giuggioli D, et al. Isolated pulmonary hypertension in diffuse cutaneous systemic sclerosis successfully treated with long-term plasma exchange. Scand J Rheum 2000; 29(3):198–200.
Binks M, Passweg JR, Furst D, McSweeney P, et al. Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: Procedure related mortality and impact on skin disease. Ann Rheum Dis 2001; 60(6):577–84.
Glikson M, Pollack A, Dresner-Feigin R, Galun E, et al. Nifedipine and prazosin in the management of pulmonary hypertension in CREST syndrome. Chest 1990; 98(3):759–61.
Alpert MA, Pressly TA, Mukerji V, Lambert CR, et al. Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. Am J Cardiol 1991; 68(17):1687–91.
Alpert MA, Pressly TA, Mukerji V, Lambert CR, et al. Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease. Chest 1992; 102(5):1407–12.
Shinohara S, Murata I, Yamada H, Sato T, et al. Combined effects of diltiazem and oxygen in pulmonary hypertension of mixed connective tissue disease. J Rheum 1994; 21(9):1763–5.
Sfikakis PP, Kyriakidis MK, Vergos CG, Vyssoulis GP, et al. Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril. Am J Med 1991; 90(5):541–6.
Klings ES, Hill NS, Ieong MH, Simms RW, et al. Systemic sclerosis-associated pulmonary hypertension: Short- and long-term effects of epoprostenol (prostacyclin). Arthritis Rheum 1999; 42(12):2638–45.
Badesch DB, Abman SH, Ahearn GS, Barst RJ, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126(1 Suppl):35S–62S.
Strange C, Bolster M, Mazur J, Taylor M, et al. Hemodynamic effects of epoprostenol in patients with systemic sclerosis and pulmonary hypertension. Chest 2000; 118(4):1077–82.
Humbert M, Sanchez O, Fartoukh M, Jagot JL, et al. Treatment of severe pulmonary hypertension secondary to connective tissue diseases with continuous IV epoprostenol (prostacyclin). Chest 1998; 114(1 Suppl):80S–82S.
Badesch DB, Tapson VF, McGoon MD, Brundage BH, 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.
Horn EM, Barst RJ, Poon M. Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus. Chest 2000; 118(4):1229–30.
de la MJ, Gomez-Sanchez MA, Aranzana M, Gomez-Reino JJ. Long-term iloprost infusion therapy for severe pulmonary hypertension in patients with connective tissue diseases. Arthritis Rheum 1994; 37(10):1528–33.
Mittag M, Beckheinrich P, Haustein UF. Systemic sclerosis-related Raynaud’s phenomenon: Effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels. Acta Derm Venereol 2001; 81(4):294–7.
Launay D, Hachulla E, Hatron PY, Goullard L, et al. Aerosolized iloprost in CREST syndrome related pulmonary hypertension. J Rheum 2001; 28(10):2252–6.
Olschewski H, Simonneau G, Galie N, Higenbottam T, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002; 347(5):322–9.
McLaughlin VV, Gaine SP, Barst RJ, Oudiz RJ, et al. Efficacy and safety of treprostinil: An epoprostenol analog for primary pulmonary hypertension. J Cardiovasc Pharmacol 2003; 41(2):293–9.
Oudiz RJ, Schilz RJ, Barst RJ, Galie N, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest 2004; 126(2):420–7.
Tapson VF, Gomberg-Maitland M, McLaughlin VV, Benza RL, et al. Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: A prospective, multicenter, open-label, 12-week trial. Chest 2006; 129(3):683–8.
Rubin LJ, Badesch DB, Barst RJ, Galie N, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346(12):896–903.
Sitbon O, Badesch DB, Channick RN, Frost A, et al. Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: A 1-year follow-up study. Chest 2003; 124(1):247–54.
Barst RJ, Langleben D, Frost A, Horn EM, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004; 169(4):441–7.
Galie N, Badesch D, Oudiz R, Simonneau G, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46(3):529–35.
Galie N, Ghofrani HA, Torbicki A, Barst RJ, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353(20):2148–57.
Rosenkranz S, Diet F, Karasch T, Weihrauch J, et al. Sildenafil improved pulmonary hypertension and peripheral blood flow in a patient with scleroderma-associated lung fibrosis and the Raynaud phenomenon. Ann Intern Med 2003; 139(10):871–3.
Rosas V, Conte JV, Yang SC, Gaine SP, et al. Lung transplantation and systemic sclerosis. Ann Transplant 2000; 5(3):38–43.
Allcock RJ, O’Sullivan JJ, Corris PA. Palliation of systemic sclerosis-associated pulmonary hypertension by atrial septostomy. Arthritis Rheum 2001; 44(7):1660–2.
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Fisher, K.A., Hill, N.S., Farber, H.W. (2008). Connective Tissue Disease Associated Pulmonary Hypertension. In: Hill, N.S., Farber, H.W. (eds) Pulmonary Hypertension. Contemporary Cardiology™. Humana Press. https://doi.org/10.1007/978-1-60327-075-5_8
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