Management of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis

References

• Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685–1699. doi:10.1016/S0140-6736(17)30933-928413064
   PubMed Web of Science ®Google Scholar
• van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737–2747. doi:10.1002/art.3809824122180
   PubMed Web of Science ®Google Scholar
• LeRoy EC, Medsger TA Jr. Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001;28(7):1573–1576.11469464
   PubMed Web of Science ®Google Scholar
• Simonneau G, Montani D. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913.30545968
   PubMed Web of Science ®Google Scholar
• Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888–894. doi:10.1183/09031936.0014560819324955
   PubMed Web of Science ®Google Scholar
• Xanthouli P, Jordan S, Milde N, et al. Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension. Ann Rheumatic Dis. 2019;79(3):370–378.
   Web of Science ®Google Scholar
• Nagel C, Marra AM, Benjamin N, et al. Reduced right ventricular output reserve in patients with systemic sclerosis and mildly elevated pulmonary artery pressure. Arthritis Rheumatol. 2019;71(5):805–816. doi:10.1002/art.2019.71.issue-530615302
   PubMed Web of Science ®Google Scholar
• Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. doi:10.1183/13993003.01913-201830545968
   PubMed Web of Science ®Google Scholar
• Chaisson NF, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. Chest. 2013;144(4):1346–1356. doi:10.1378/chest.12-239624081346
   PubMed Web of Science ®Google Scholar
• Avouac J, Airo P, Meune C, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol. 2010;37(11):2290–2298. doi:10.3899/jrheum.10024520810505
   PubMed Web of Science ®Google Scholar
• Khanna D, Gladue H, Channick R, et al. Recommendations for screening and detection of connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):3194–3201. doi:10.1002/art.3817224022584
   PubMed Web of Science ®Google Scholar
• Johnson SR, Granton JT. Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus. Eur Respir Rev. 2011;20(122):277–286. doi:10.1183/09059180.0000381122130821
   PubMedGoogle Scholar
• Coghlan JG, Denton CP, Grunig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–1349. doi:10.1136/annrheumdis-2013-20330123687283
   PubMed Web of Science ®Google Scholar
• Fisher MR, Mathai SC, Champion HC, et al. Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum. 2006;54(9):3043–3050. doi:10.1002/(ISSN)1529-013116947776
   PubMed Web of Science ®Google Scholar
• Launay D, Sobanski V, Hachulla E, Humbert M. Pulmonary hypertension in systemic sclerosis: different phenotypes. Eur Respir Rev. 2017;26(145):170056. doi:10.1183/16000617.0056-201728954767
   PubMed Web of Science ®Google Scholar
• Lambova S. Cardiac manifestations in systemic sclerosis. World J Cardiol. 2014;6(9):993–1005. doi:10.4330/wjc.v6.i9.99325276300
   PubMedGoogle Scholar
• de Groote P, Gressin V, Hachulla E, et al. Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann Rheum Dis. 2008;67(1):31–36. doi:10.1136/ard.2006.05776017267515
   PubMed Web of Science ®Google Scholar
• Fernandez-Codina A, Simeon-aznar CP, Pinal-Fernandez I, et al. Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival. Rheumatol Int. 2017;37(1):75–84. doi:10.1007/s00296-015-3382-226497313
   PubMed Web of Science ®Google Scholar
• Vachiery JL, Adir Y, Barbera JA, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D100–D108. doi:10.1016/j.jacc.2013.10.03324355634
   PubMed Web of Science ®Google Scholar
• Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119. doi:10.1093/eurheartj/ehv31726320113
   PubMed Web of Science ®Google Scholar
• Vachiery JL, Delcroix M. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J. 2018;51(2):1701886.29437943
   PubMed Web of Science ®Google Scholar
• Hinchcliff M, Fischer A, Schiopu E, Steen VD. Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS): baseline characteristics and description of study population. J Rheumatol. 2011;38(10):2172–2179. doi:10.3899/jrheum.10124321844142
   PubMed Web of Science ®Google Scholar
• Schoenfeld SR, Castelino FV. Interstitial lung disease in scleroderma. Rheum Dis Clin North Am. 2015;41(2):237–248. doi:10.1016/j.rdc.2014.12.00525836640
   PubMed Web of Science ®Google Scholar
• Hurdman J, Condliffe R, Elliot CA, et al. ASPIRE registry: assessing the spectrum of pulmonary hypertension identified at a REferral centre. Eur Respir J. 2012;39(4):945–955. doi:10.1183/09031936.0007841121885399
   PubMed Web of Science ®Google Scholar
• Cappelli S, Bellando Randone S, Camiciottoli G, De Paulis A, Guiducci S, Matucci-Cerinic M. Interstitial lung disease in systemic sclerosis: where do we stand? Eur Respir Rev. 2015;24(137):411–419. doi:10.1183/16000617.0000291526324802
   PubMedGoogle Scholar
• Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med. 2019;380(26):2518–2528.31112379
   PubMed Web of Science ®Google Scholar
• Huang J, Maier C, Zhang Y, et al. Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis. Ann Rheum Dis. 2017;76(11):1941–1948. doi:10.1136/annrheumdis-2016-21082328814429
   PubMed Web of Science ®Google Scholar
• Young A, Vummidi D, Visovatti S, et al. Prevalence, treatment, and outcomes of coexistent pulmonary hypertension and interstitial lung disease in systemic sclerosis. Arthritis Rheumatol. 2019;71(8):1339–1349. doi:10.1002/art.v71.830762947
   PubMed Web of Science ®Google Scholar
• Gupta S, Gupta A, Rehman S, et al. Pulmonary veno-occlusive disease is highly prevalent in scleroderma patients undergoing lung transplantation. ERJ Open Res. 2019;5(1):00168–2018. doi:10.1183/23120541.00168-201830775371
   PubMedGoogle Scholar
• Humbert M, Guignabert C. Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019;53(1):1801887.30545970
   PubMed Web of Science ®Google Scholar
• Schoenfeld SR, Choi HK, Sayre EC, Avina-zubieta JA. Risk of pulmonary embolism and deep venous thrombosis in systemic sclerosis: a general population-based study. Arthritis Care Res. 2016;68(2):246–253. doi:10.1002/acr.22673
   Web of Science ®Google Scholar
• Martinez C, Wallenhorst C, Teal S, Cohen AT, Peacock AJ. Incidence and risk factors of chronic thromboembolic pulmonary hypertension following venous thromboembolism, a population-based cohort study in England. Pulm Circ. 2018;8(3):2045894018791358. doi:10.1177/204589401879135829985100
   PubMed Web of Science ®Google Scholar
• Bonderman D, Turecek PL, Jakowitsch J, et al. High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension. Thromb Haemost. 2003;90(3):372–376. doi:10.1160/TH03-02-006712958604
   PubMed Web of Science ®Google Scholar
• Pendergrass SA, Hayes E, Farina G, et al. Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury. PLoS One. 2010;5(8):e12106. doi:10.1371/journal.pone.001210620808962
   PubMed Web of Science ®Google Scholar
• Pepke-zaba J, Delcroix M, Lang I, et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation. 2011;124(18):1973–1981. doi:10.1161/CIRCULATIONAHA.110.01500821969018
   PubMed Web of Science ®Google Scholar
• Kim NH, Delcroix M, Jais x. Chronic thromboembolic pulmonary hypertension. Eur Respir J. 2019;53(1):1801915.30545969
   PubMed Web of Science ®Google Scholar
• Allanore Y, Borderie D, Meune C, 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):3503–3508. doi:10.1002/(ISSN)1529-013114674001
   PubMed Web of Science ®Google Scholar
• Ahmed M, Dweik RA, Tonelli AR. What is the best approach to a high systolic pulmonary artery pressure on echocardiography? Cleve Clin J Med. 2016;83(4):256–260. doi:10.3949/ccjm.83a.1418627055199
   PubMed Web of Science ®Google Scholar
• Schwaiger JP, Khanna D, Gerry Coghlan J. Screening patients with scleroderma for pulmonary arterial hypertension and implications for other at-risk populations. Eur Respir Rev. 2013;22(130):515–525. doi:10.1183/09059180.0000601324293467
   PubMedGoogle Scholar
• Zompatori M, Leone MB, Giannotta M, et al. Pulmonary hypertension and systemic sclerosis: the role of high-resolution computed tomography. Radiol Med. 2013;118(8):1360–1372. doi:10.1007/s11547-013-0934-123716290
   PubMed Web of Science ®Google Scholar
• Frost A, Badesch D, Gibbs JSR, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019;53(1):1801904. doi:10.1183/13993003.01904-201830545972
   PubMed Web of Science ®Google Scholar
• Camargo VM, Martins Bdo C, Jardim C, Fernandes CJ, Hovnanian A, Souza R. Validation of a treadmill six-minute walk test protocol for the evaluation of patients with pulmonary arterial hypertension. J Bras De Pneumol. 2009;35(5):423–430. doi:10.1590/S1806-37132009000500006
   PubMed Web of Science ®Google Scholar
• Minai OA, Nguyen Q, Mummadi S, Walker E, McCarthy K, Dweik RA. Heart rate recovery is an important predictor of outcomes in patients with connective tissue disease-associated pulmonary hypertension. Pulm Circ. 2015;5(3):565–576. doi:10.1086/68243226401258
   PubMed Web of Science ®Google Scholar
• Gadre A, Ghattas C, Han X, Wang X, Minai O, Highland KB. Six-minute walk test as a predictor of diagnosis, disease severity, and clinical outcomes in scleroderma-associated pulmonary hypertension: the DIBOSA study. Lung. 2017;195(5):529–536. doi:10.1007/s00408-017-0034-128646245
   PubMed Web of Science ®Google Scholar
• Hachulla AL, Launay D, Gaxotte V, et al. Cardiac magnetic resonance imaging in systemic sclerosis: a cross-sectional observational study of 52 patients. Ann Rheum Dis. 2009;68(12):1878–1884. doi:10.1136/ard.2008.09583619054830
   PubMed Web of Science ®Google Scholar
• Bezante GP, Rollando D, Sessarego M, et al. Cardiac magnetic resonance imaging detects subclinical right ventricular impairment in systemic sclerosis. J Rheumatol. 2007;34(12):2431–2437.17985401
   PubMed Web of Science ®Google Scholar
• Humbert M, Gerry Coghlan J, Khanna D. Early detection and management of pulmonary arterial hypertension. Eur Respir Rev. 2012;21(126):306–312. doi:10.1183/09059180.0000511223204118
   PubMedGoogle Scholar
• Morrisroe K, Stevens W, Huq M, et al. Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension. Arthritis Res Ther. 2017;19(1):122. doi:10.1186/s13075-017-1341-x28576149
   PubMed Web of Science ®Google Scholar
• Vachiery JL, Coghlan G. Screening for pulmonary arterial hypertension in systemic sclerosis. Eur Respir Rev. 2009;18(113):162–169. doi:10.1183/09059180.0000320920956137
   PubMedGoogle Scholar
• Thakkar V, Stevens WM, Prior D, et al. N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis: a case-control study. Arthritis Res Ther. 2012;14(3):R143. doi:10.1186/ar387622691291
   PubMed Web of Science ®Google Scholar
• Kowal-bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327–1339. doi:10.1136/annrheumdis-2016-20990927941129
   PubMed Web of Science ®Google Scholar
• Galie N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. doi:10.1183/13993003.01889-201830545971
   PubMed Web of Science ®Google Scholar
• Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting survival in patients with pulmonary arterial hypertension: the REVEAL risk score calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies. Chest. 2019;156(2):323–337. doi:10.1016/j.chest.2019.02.00430772387
   PubMed Web of Science ®Google Scholar
• 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(9):1023–1030. doi:10.1164/rccm.200510-1668OC16456139
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50(2):1700740.28775047
   PubMed Web of Science ®Google Scholar
• Kylhammar D, Kjellstrom B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39(47):4175–4181. doi:10.1093/eurheartj/ehx25728575277
   PubMed Web of Science ®Google Scholar
• Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50(2):1700889. doi:10.1183/13993003.00889-201728775050
   PubMed Web of Science ®Google Scholar
• Frech T, Walker AE, Barrett-o’keefe Z, et al. Systemic sclerosis induces pronounced peripheral vascular dysfunction characterized by blunted peripheral vasoreactivity and endothelial dysfunction. Clin Rheumatol. 2015;34(5):905–913. doi:10.1007/s10067-014-2834-525511849
   PubMed Web of Science ®Google Scholar
• Chatterjee S. Pulmonary hypertension in systemic sclerosis. Semin Arthritis Rheum. 2011;41(1):19–37. doi:10.1016/j.semarthrit.2010.08.00421047671
   PubMed Web of Science ®Google Scholar
• Galie N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th world symposium on pulmonary hypertension. Eur Respir J. 2019;53(1):1802148. doi:10.1183/13993003.02148-201830552088
   PubMed Web of Science ®Google Scholar
• Barnett CF, Machado RF. Sildenafil in the treatment of pulmonary hypertension. Vasc Health Risk Manag. 2006;2(4):411–422. doi:10.2147/vhrm.2006.2.issue-417323595
   PubMedGoogle Scholar
• Khaybullina D, Patel A, Zerilli T. Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P TPeer-Rev J Formulary Manage. 2014;39(11):749–758.
   PubMedGoogle Scholar
• Galie N, Muller K, Scalise AV, Grunig E. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur Respir J. 2015;45(5):1314–1322. doi:10.1183/09031936.0010591425657022
   PubMed Web of Science ®Google Scholar
• Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–2157. doi:10.1056/NEJMoa05001016291984
   PubMed Web of Science ®Google Scholar
• Badesch DB, Hill NS, Burgess G, et al. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease. J Rheumatol. 2007;34(12):2417–2422.17985403
   PubMed Web of Science ®Google Scholar
• Galie N, Brundage BH, Ghofrani HA, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894–2903. doi:10.1161/CIRCULATIONAHA.108.83927419470885
   PubMed Web of Science ®Google Scholar
• Galie N, Denton CP, Dardi F, et al. Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease. Int J Cardiol. 2017;235:67–72. doi:10.1016/j.ijcard.2017.02.09428279499
   PubMed Web of Science ®Google Scholar
• Ghofrani HA, Galie N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–340. doi:10.1056/NEJMoa120965523883378
   PubMed Web of Science ®Google Scholar
• Humbert M, Coghlan JG, Ghofrani HA, et al. Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann Rheum Dis. 2017;76(2):422–426. doi:10.1136/annrheumdis-2015-20908727457511
   PubMed Web of Science ®Google Scholar
• Raina A, Benza RL, Farber HW. Replacing a phosphodiesterase-5 inhibitor with riociguat in patients with connective tissue disease-associated pulmonary arterial hypertension: a case series. Pulm Circ. 2017;7(3):741–746. doi:10.1177/204589321772169428671485
   PubMed Web of Science ®Google Scholar
• Marra AM, Halank M, Benjamin N, et al. Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study). Respir Res. 2018;19(1):258. doi:10.1186/s12931-018-0957-y30567595
   PubMed Web of Science ®Google Scholar
• Marra AM, Egenlauf B, Ehlken N, et al. Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Int J Cardiol. 2015;195:19–26. doi:10.1016/j.ijcard.2015.05.10526011408
   PubMed Web of Science ®Google Scholar
• Chester AH, Yacoub MH. The role of endothelin-1 in pulmonary arterial hypertension. Global Cardiology Sci Pract. 2014;2014(2):62–78. doi:10.5339/gcsp.2014.29
   Google Scholar
• Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903. doi:10.1056/NEJMoa01221211907289
   PubMed Web of Science ®Google Scholar
• 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. Circulation. 2008;117(23):3010–3019. doi:10.1161/CIRCULATIONAHA.107.74251018506008
   PubMed Web of Science ®Google Scholar
• Fischer A, Denton CP, Matucci-Cerinic M, et al. Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial. Respir Med. 2016;117:254–263. doi:10.1016/j.rmed.2016.06.01827492539
   PubMed Web of Science ®Google Scholar
• Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–818. doi:10.1056/NEJMoa121391723984728
   PubMed Web of Science ®Google Scholar
• Rhee RL, Gabler NB, Sangani S, Praestgaard A, Merkel PA, Kawut SM. Comparison of treatment response in idiopathic and connective tissue disease-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2015;192(9):1111–1117. doi:10.1164/rccm.201507-1456OC26291092
   PubMed Web of Science ®Google Scholar
• Matucci-Cerinic M, Denton CP, Furst DE, et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2011;70(1):32–38. doi:10.1136/ard.2010.13065820805294
   PubMed Web of Science ®Google Scholar
• Del Pozo R, Hernandez Gonzalez I, Escribano-subias P. The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med. 2017;11(6):491–503. doi:10.1080/17476348.2017.131759928399721
   PubMed Web of Science ®Google Scholar
• Tapson VF, Torres F, Kermeen F, 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):1383–1390. doi:10.1378/chest.11-221222628490
   PubMed Web of Science ®Google Scholar
• 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(6):425–434. doi:10.7326/0003-4819-132-6-200003210-0000210733441
   PubMed Web of Science ®Google Scholar
• Klings ES, Hill NS, Ieong MH, Simms RW, Korn JH, Farber HW. Systemic sclerosis-associated pulmonary hypertension: short- and long-term effects of epoprostenol (prostacyclin). Arthritis Rheum. 1999;42(12):2638–2645. doi:10.1002/(ISSN)1529-013110616012
   PubMed Web of Science ®Google Scholar
• Launay D, Hachulla E, Hatron PY, et al. Aerosolized iloprost in CREST syndrome related pulmonary hypertension. J Rheumatol. 2001;28(10):2252–2256.11669165
   PubMed Web of Science ®Google Scholar
• Li JH, Zhang HD, Wang ZZ, et al. Acute iloprost inhalation improves right ventricle function in pulmonary artery hypertension: a cardiac magnetic resonance study. Front Pharmacol. 2018;9:1550. doi:10.3389/fphar.2018.0155030719004
   PubMed Web of Science ®Google Scholar
• 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(3):683–688. doi:10.1378/chest.129.3.68316537868
   PubMed Web of Science ®Google Scholar
• Oudiz RJ, Schilz RJ, Barst RJ, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest. 2004;126(2):420–427. doi:10.1378/chest.126.2.42015302727
   PubMed Web of Science ®Google Scholar
• 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(6):800–804. doi:10.1164/ajrccm.165.6.210607911897647
   PubMed Web of Science ®Google Scholar
• Caravita S, Wu SC, Secchi MB, Dadone V, Bencini C, Pierini S. Long-term effects of intermittent Iloprost infusion on pulmonary arterial pressure in connective tissue disease. Eur J Intern Med. 2011;22(5):518–521. doi:10.1016/j.ejim.2011.02.00521925064
   PubMed Web of Science ®Google Scholar
• Gaine S, Chin K, Coghlan G, et al. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur Respir J. 2017;50(2):1602493. doi:10.1183/13993003.02493-201628818881
   PubMed Web of Science ®Google Scholar
• Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373(26):2522–2533. doi:10.1056/NEJMoa150318426699168
   PubMed Web of Science ®Google Scholar
• Hassoun PM, Zamanian RT, Damico R, et al. Ambrisentan and tadalafil up-front combination therapy in scleroderma-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2015;192(9):1102–1110. doi:10.1164/rccm.201507-1398OC26360334
   PubMed Web of Science ®Google Scholar
• Coghlan JG, Galie N, Barbera JA, et al. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann Rheum Dis. 2017;76(7):1219–1227. doi:10.1136/annrheumdis-2016-21023628039187
   PubMed Web of Science ®Google Scholar
• Jansa P, Pulido T. Macitentan in pulmonary arterial hypertension: a focus on combination therapy in the SERAPHIN trial. Am J Cardiovasc Drugs. 2018;18(1):1–11. doi:10.1007/s40256-017-0260-129280064
   PubMed Web of Science ®Google Scholar
• Coghlan JG, Channick R, Chin K, et al. Targeting the prostacyclin pathway with selexipag in patients with pulmonary arterial hypertension receiving double combination therapy: insights from the randomized controlled GRIPHON study. Am J Cardiovasc Drugs. 2018;18(1):37–47. doi:10.1007/s40256-017-0262-z29307087
   PubMed Web of Science ®Google Scholar
• Barst RJ, Gibbs JS, Ghofrani HA, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S78–S84. doi:10.1016/j.jacc.2009.04.01719555861
   PubMed Web of Science ®Google Scholar
• Olsson KM, Delcroix M, Ghofrani HA, et al. Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation. 2014;129(1):57–65. doi:10.1161/CIRCULATIONAHA.113.00452624081973
   PubMed Web of Science ®Google Scholar
• Preston IR, Roberts KE, Miller DP, et al. Effect of warfarin treatment on survival of patients with Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Circulation. 2015;132(25):2403–2411. doi:10.1161/CIRCULATIONAHA.115.01843526510696
   PubMed Web of Science ®Google Scholar
• Ascha M, Zhou X, Rao Y, Minai OA, Tonelli AR. Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil. Cardiovasc Ther. 2017;35(5):e12281. doi:10.1111/cdr.2017.35.issue-5
   Web of Science ®Google Scholar
• Calderone A, Stevens W, Prior D, et al. Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol. BMJ Open. 2016;6(12):e011028. doi:10.1136/bmjopen-2016-011028
   Web of Science ®Google Scholar
• Aithala R, Alex AG, Danda D. Pulmonary hypertension in connective tissue diseases: an update. Int J Rheum Dis. 2017;20(1):5–24. doi:10.1111/1756-185X.1300128205373
   PubMed Web of Science ®Google Scholar
• Sanchez O, Sitbon O, Jais X, Simonneau G, Humbert M. Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension. Chest. 2006;130(1):182–189. doi:10.1378/chest.130.1.18216840400
   PubMed Web of Science ®Google Scholar
• Sweiss NJ, Hushaw L, Thenappan T, et al. Diagnosis and management of pulmonary hypertension in systemic sclerosis. Curr Rheumatol Rep. 2010;12(1):8–18. doi:10.1007/s11926-009-0078-120425528
   PubMedGoogle Scholar
• Galie N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60–D72. doi:10.1016/j.jacc.2013.10.03124355643
   PubMed Web of Science ®Google Scholar
• Grunig E, Maier F, Ehlken N, et al. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases. Arthritis Res Ther. 2012;14(3):R148. doi:10.1186/ar388322709477
   PubMed Web of Science ®Google Scholar
• Miniati I, Guiducci S, Mecacci F, Mello G, Matucci-Cerinic M. Pregnancy in systemic sclerosis. Rheumatol. 2008;47(Suppl 3):iii16–iii18. doi:10.1093/rheumatology/ken174
   Web of Science ®Google Scholar
• Kawut SM, Taichman DB, Archer-chicko CL, Palevsky HI, Kimmel SE. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest. 2003;123(2):344–350. doi:10.1378/chest.123.2.34412576350
   PubMed Web of Science ®Google Scholar
• Allcock RJ, O’sullivan JJ, Corris PA. Palliation of systemic sclerosis-associated pulmonary hypertension by atrial septostomy. Arthritis Rheum. 2001;44(7):1660–1662. doi:10.1002/(ISSN)1529-013111465717
   PubMed Web of Science ®Google Scholar
• Schachna L, Medsger TA Jr, Dauber JH, et al. Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension. Arthritis Rheum. 2006;54(12):3954–3961. doi:10.1002/(ISSN)1529-013117133609
   PubMed Web of Science ®Google Scholar
• Gadre SK, Minai OA, Wang XF, Zhang Q, Budev M, Tonelli AR. Lung or heart-lung transplant in pulmonary arterial hypertension: what is the impact of systemic sclerosis? Exp Clin Transplant. 2017;15(6):676–684. doi:10.6002/ect.2016.020928540841
   PubMed Web of Science ®Google Scholar
• Shah RJ, Boin F. Lung transplantation in patients with systemic sclerosis. Curr Rheumatol Rep. 2017;19(5):23. doi:10.1007/s11926-017-0650-z28386760
   PubMed Web of Science ®Google Scholar
• Fernandez-codina A, Berastegui C, Pinal-fernandez I, et al. Lung transplantation in systemic sclerosis: a single center cohort study. Joint Bone Spine. 2018;85(1):79–84. doi:10.1016/j.jbspin.2017.03.01228408277
   PubMed Web of Science ®Google Scholar
• Sottile PD, Iturbe D, Katsumoto TR, et al. Outcomes in systemic sclerosis-related lung disease after lung transplantation. Transplantation. 2013;95(7):975–980. doi:10.1097/TP.0b013e3182845f2323545509
   PubMed Web of Science ®Google Scholar
• Lefevre G, Dauchet L, Hachulla E, et al. Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Arthritis Rheum. 2013;65(9):2412–2423. doi:10.1002/art.3802923740572
   PubMed Web of Science ®Google Scholar
• Chung L, Farber HW, Benza R, et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest. 2014;146(6):1494–1504. doi:10.1378/chest.13-301424992469
   PubMed Web of Science ®Google Scholar
• Chung L, Domsic RT, Lingala B, et al. Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry. Arthritis Care Res (Hoboken). 2014;66(3):489–495. doi:10.1002/acr.v66.323983198
   PubMed Web of Science ®Google Scholar
• Sobanski V, Giovannelli J, Lynch BM, et al. Characteristics and Survival of anti-U1 RNP antibody-positive patients with connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheumatol. 2016;68(2):484–493. doi:10.1002/art.3943226415038
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. A phase 2 multicenter, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of ifetroban in patients with diffuse cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension (SSc-PAH). NCT02682511 Available from: https://clinicaltrials.gov/ct2/show/NCT02682511. Accessed 36, 2020.
   Google Scholar
• Center NIoHC. A randomized, double-blind, placebo-controlled, phASE II Multicenter trial of a monoclonal antibody to CD20 (Rituximab) for the Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH). NCT01086540 Available from: https://clinicaltrials.gov/ct2/show/NCT01086540. Accessed 36, 2020.
   Google Scholar
• Zamanian R, Badesch D, Chung L, et al. Late Breaking Abstract - Safety and efficacy of B-cell depletion with rituximab for the treatment of systemic sclerosis-associated pulmonary arterial hypertension. Eur Respir J. 2019;54(suppl63):RCT1884.
   Google Scholar
• ClinicalTrials.gov. A dose-ranging study of the efficacy and safety of bardoxolone methyl in patients with pulmonary hypertension. NCT02036970 [5 16, 2018]. Available from: https://clinicaltrials.gov/ct2/show/NCT02036970. Accessed 36, 2020.
   Google Scholar