{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T02:32:25Z","timestamp":1761964345258,"version":"3.40.4"},"reference-count":58,"publisher":"European Respiratory Society (ERS)","issue":"122","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir Rev"],"accepted":{"date-parts":[[2011,9,6]]},"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p>Over the past decade, awareness among the medical profession of pulmonary arterial hypertension (PAH) being a treatable disease has increased. Despite this, approximately one-fifth of newly diagnosed patients are classified as being in the most severely compromised functional class (<jats:italic>i.e.<\/jats:italic>New York Health Association\/World Health Organization functional class (NYHA\/WHO FC) IV). The prognosis for patients in NYHA\/WHO FC IV is poor, with 3-yr survival being around 40%, even with treatment. Poor prognosis coupled with severe functional impairment means it is vital that these patients receive optimal treatment. There are also subgroups of patients, who, although classified as NYHA\/WHO FC III, may actually be severely haemodynamically compromised and at risk of rapid deterioration. Such subgroups include patients with PAH associated with systemic sclerosis or certain heritable mutations. These patients should be considered as being at the more severe end of the disease spectrum. In this article we will discuss the optimal management of patients with severe PAH. This includes newly emerging evidence from small-scale, open-label studies that use upfront combination therapy with intravenous epoprostenol plus oral PAH-specific drugs. We also review treatment strategies that may offer clinical benefits to patients with more severe PAH.<\/jats:p>","DOI":"10.1183\/09059180.00007011","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T13:24:13Z","timestamp":1322832253000},"page":"254-261","source":"Crossref","is-referenced-by-count":16,"title":["Optimal management of severe pulmonary arterial hypertension"],"prefix":"10.1183","volume":"20","author":[{"given":"O.","family":"Sitbon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Simonneau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2011,11,30]]},"reference":[{"key":"2025042404454367000_20.122.254.1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-11-12"},{"key":"2025042404454367000_20.122.254.2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp022"},{"key":"2025042404454367000_20.122.254.3","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00072709"},{"key":"2025042404454367000_20.122.254.4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.911818"},{"key":"2025042404454367000_20.122.254.5","first-page":"371","article-title":"Pulmonary hypertension in Switzerland: treatment and clinical course","volume":"138","author":"Fischler","year":"2008","journal-title":"Swiss Med Wkly"},{"key":"2025042404454367000_20.122.254.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.898122"},{"key":"2025042404454367000_20.122.254.7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep398"},{"key":"2025042404454367000_20.122.254.8","first-page":"379","article-title":"Epidemiology of pulmonary hypertension: new data from the Swiss registry","volume":"138","author":"Tueller","year":"2008","journal-title":"Swiss Med Wkly"},{"key":"2025042404454367000_20.122.254.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02012-0"},{"key":"2025042404454367000_20.122.254.10","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200510-1668OC"},{"key":"2025042404454367000_20.122.254.11","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-5-343"},{"key":"2025042404454367000_20.122.254.12","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000029100.82385.58"},{"key":"2025042404454367000_20.122.254.13","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp297"},{"key":"2025042404454367000_20.122.254.14","doi-asserted-by":"publisher","DOI":"10.1378\/chest.123.2.344"},{"key":"2025042404454367000_20.122.254.15","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00057010"},{"key":"2025042404454367000_20.122.254.16","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200806-953OC"},{"key":"2025042404454367000_20.122.254.17","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep449"},{"key":"2025042404454367000_20.122.254.18","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200712-1807OC"},{"key":"2025042404454367000_20.122.254.19","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200908-1284OC"},{"key":"2025042404454367000_20.122.254.20","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-2913"},{"key":"2025042404454367000_20.122.254.21","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1140"},{"key":"2025042404454367000_20.122.254.22","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-112-7-485"},{"key":"2025042404454367000_20.122.254.23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340504"},{"key":"2025042404454367000_20.122.254.24","doi-asserted-by":"crossref","first-page":"425","DOI":"10.7326\/0003-4819-132-6-200003210-00002","article-title":"Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial","volume":"132","author":"Badesch","year":"2000","journal-title":"Ann Intern Med"},{"key":"2025042404454367000_20.122.254.25","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.6.2106079"},{"key":"2025042404454367000_20.122.254.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01786-2"},{"key":"2025042404454367000_20.122.254.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00463-7"},{"key":"2025042404454367000_20.122.254.28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020204"},{"key":"2025042404454367000_20.122.254.29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012212"},{"key":"2025042404454367000_20.122.254.30","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.742510"},{"key":"2025042404454367000_20.122.254.31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050010"},{"key":"2025042404454367000_20.122.254.32","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.839274"},{"key":"2025042404454367000_20.122.254.33","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-6-199409150-00003"},{"key":"2025042404454367000_20.122.254.34","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.081277"},{"key":"2025042404454367000_20.122.254.35","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00028404"},{"key":"2025042404454367000_20.122.254.36","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200603-358OC"},{"key":"2025042404454367000_20.122.254.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.06.083"},{"key":"2025042404454367000_20.122.254.38","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00075305"},{"key":"2025042404454367000_20.122.254.39","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00057906"},{"key":"2025042404454367000_20.122.254.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2006.09.016"},{"key":"2025042404454367000_20.122.254.41","doi-asserted-by":"publisher","DOI":"10.1253\/circj.72.1142"},{"key":"2025042404454367000_20.122.254.42","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-149-8-200810210-00004"},{"key":"2025042404454367000_20.122.254.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.01.027"},{"key":"2025042404454367000_20.122.254.44","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00003809"},{"issue":"Suppl. 6","key":"2025042404454367000_20.122.254.45","doi-asserted-by":"crossref","first-page":"622S","DOI":"10.1378\/chest.128.6_suppl.622S","article-title":"Clinical challenges in pulmonary hypertension: Roger S. Mitchell lecture","volume":"128","author":"Provencher","year":"2005","journal-title":"Chest"},{"key":"2025042404454367000_20.122.254.46","doi-asserted-by":"crossref","unstructured":"Kemp K Savale L O\u2032Callaghan DS . Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study J Heart Lung Transplant 2011 [In press].","DOI":"10.1016\/j.healun.2011.11.002"},{"key":"2025042404454367000_20.122.254.47","first-page":"A5910","article-title":"Upfront triple combination therapy of i.v. epoprostenol with oral bosentan and sildenafil in idiopathic and heritable pulmonary arterial hypertension","volume":"183","author":"Sitbon","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2025042404454367000_20.122.254.48","unstructured":"A study of first-line ambrisentan and tadalafil combination therapy in subjects with pulmonary arterial hypertension (PAH) (AMBITION). http:\/\/clinicaltrials.gov\/ct2\/show\/NCT01178073 Date last updated: May 26, 2011. Date last accessed: August 30, 2011."},{"key":"2025042404454367000_20.122.254.49","unstructured":"Treprostinil combined with tadalafil for pulmonary hypertension (T2). http:\/\/clinicaltrials.gov\/ct2\/show\/NCT01302444. Date last updated: June 10, 2011. Date last accessed: August 30, 2011."},{"key":"2025042404454367000_20.122.254.50","unstructured":"First-line bosentan and sildenafil combination therapy for pulmonary arterial hypertension. http:\/\/clinicaltrials.gov\/ct2\/show\/NCT01247116. Date last updated: November 23, 2010. Date last accessed August 30, 2011."},{"key":"2025042404454367000_20.122.254.51","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-1227"},{"key":"2025042404454367000_20.122.254.52","doi-asserted-by":"publisher","DOI":"10.1097\/00019501-200502000-00004"},{"key":"2025042404454367000_20.122.254.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.016"},{"key":"2025042404454367000_20.122.254.54","doi-asserted-by":"crossref","unstructured":"Sandoval J Gaspar J Pe\u00f1a H . Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension. Eur Respir J 2011; 38: 1343\u20131348.","DOI":"10.1183\/09031936.00072210"},{"key":"2025042404454367000_20.122.254.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.017"},{"key":"2025042404454367000_20.122.254.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2010.08.004"},{"key":"2025042404454367000_20.122.254.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2010.02.039"},{"key":"2025042404454367000_20.122.254.58","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(01)00420-X"}],"container-title":["European Respiratory Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/09059180.00007011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T11:45:58Z","timestamp":1745495158000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/09059180.00007011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,30]]},"references-count":58,"journal-issue":{"issue":"122","published-online":{"date-parts":[[2011,11,30]]},"published-print":{"date-parts":[[2011,12]]}},"alternative-id":["10.1183\/09059180.00007011"],"URL":"https:\/\/doi.org\/10.1183\/09059180.00007011","relation":{},"ISSN":["0905-9180","1600-0617"],"issn-type":[{"type":"print","value":"0905-9180"},{"type":"electronic","value":"1600-0617"}],"subject":[],"published":{"date-parts":[[2011,11,30]]}}}