{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:13:38Z","timestamp":1793258018611,"version":"4.5.0"},"reference-count":111,"publisher":"Elsevier BV","issue":"18","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T00:00:00Z","timestamp":1463011200000},"content-version":"vor","delay-in-days":377,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["clinicalkey.jp","onlinejacc.org","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of the American College of Cardiology"],"published-print":{"date-parts":[[2015,5]]},"DOI":"10.1016\/j.jacc.2015.03.540","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T14:16:03Z","timestamp":1430748963000},"page":"1976-1997","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":341,"title":["Management of Pulmonary Arterial\u00a0Hypertension"],"prefix":"10.1016","volume":"65","author":[{"given":"Vallerie V.","family":"McLaughlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogerio","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jacc.2015.03.540_bib1","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1093\/eurheartj\/ehp297","volume":"30","author":"Galie","year":"2009","journal-title":"Eur Heart J"},{"key":"10.1016\/j.jacc.2015.03.540_bib2","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.jacc.2009.01.004","article-title":"ACCF\/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association","volume":"53","author":"McLaughlin","year":"2009","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib3","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1183\/09031936.00145608","article-title":"Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review","volume":"34","author":"Kovacs","year":"2009","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib4","doi-asserted-by":"crossref","first-page":"D42","DOI":"10.1016\/j.jacc.2013.10.032","article-title":"Definitions and diagnosis of pulmonary hypertension","volume":"62","author":"Hoeper","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib5","doi-asserted-by":"crossref","first-page":"D34","DOI":"10.1016\/j.jacc.2013.10.029","article-title":"Updated clinical classification of pulmonary hypertension","volume":"62","author":"Simonneau","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib6","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1164\/rccm.200602-165OC","article-title":"High frequency of BMPR2 exonic deletions\/duplications\u00a0in familial pulmonary arterial hypertension","volume":"174","author":"Cogan","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib7","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/jmg.37.10.741","article-title":"Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family","volume":"37","author":"Thomson","year":"2000","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.jacc.2015.03.540_bib8","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/jmg.40.12.865","article-title":"Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia","volume":"40","author":"Harrison","year":"2003","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.jacc.2015.03.540_bib9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1161\/CIRCGENETICS.111.961888","article-title":"Whole exome\u00a0sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension","volume":"5","author":"Austin","year":"2012","journal-title":"Circ Cardiovasc Genet"},{"key":"10.1016\/j.jacc.2015.03.540_bib10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa1211097","article-title":"A\u00a0novel channelopathy in pulmonary arterial hypertension","volume":"369","author":"Ma","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib11","first-page":"160","article-title":"Aminorex and pulmonary hypertension. A review","volume":"27","author":"Gurtner","year":"1985","journal-title":"Cor Vasa"},{"key":"10.1016\/j.jacc.2015.03.540_bib12","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00104807","article-title":"Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases","volume":"31","author":"Souza","year":"2008","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib13","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1183\/09031936.00188611","article-title":"Pulmonary hypertension associated with benfluorex exposure","volume":"40","author":"Savale","year":"2012","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib14","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1161\/CIRCULATIONAHA.111.079921","article-title":"Pulmonary arterial hypertension in patients treated by dasatinib","volume":"125","author":"Montani","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib15","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1183\/09031936.00057914","article-title":"Pulmonary arterial hypertension in patients treated with interferon","volume":"44","author":"Savale","year":"2014","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib16","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1164\/rccm.200510-1668OC","article-title":"Pulmonary arterial hypertension in France: results from a national registry","volume":"173","author":"Humbert","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib17","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1378\/chest.09-1140","article-title":"Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry","volume":"137","author":"Badesch","year":"2010","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib18","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1002\/art.30541","article-title":"Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival","volume":"63","author":"Humbert","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jacc.2015.03.540_bib19","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1136\/annrheumdis-2013-203301","article-title":"Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study","volume":"73","author":"Coghlan","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jacc.2015.03.540_bib20","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1055\/s-0029-1233313","article-title":"Pulmonary arterial hypertension and HIV infection","volume":"30","author":"Degano","year":"2009","journal-title":"Semin Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1164\/rccm.200704-541OC","article-title":"Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era","volume":"177","author":"Sitbon","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib22","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1378\/chest.11-1460","article-title":"An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry","volume":"142","author":"Benza","year":"2012","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib23","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1378\/chest.11-0160","article-title":"Portopulmonary hypertension: a report from the US-based REVEAL Registry","volume":"141","author":"Krowka","year":"2012","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib24","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1136\/hrt.2006.098848","article-title":"Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease","volume":"93","author":"Engelfriet","year":"2007","journal-title":"Heart"},{"key":"10.1016\/j.jacc.2015.03.540_bib25","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1161\/CIRCULATIONAHA.108.803221","article-title":"Cardiopulmonary manifestations of hepatosplenic schistosomiasis","volume":"119","author":"Lapa","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.jacc.2010.03.065","article-title":"Survival in schistosomiasis-associated pulmonary arterial hypertension","volume":"56","author":"dos Santos Fernandes","year":"2010","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib27","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1378\/chest.11-0483","article-title":"The role of target therapies in schistosomiasis-associated pulmonary arterial hypertension","volume":"141","author":"Fernandes","year":"2012","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib28","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1183\/09031936.00090608","article-title":"Pulmonary veno-occlusive disease","volume":"33","author":"Montani","year":"2009","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib29","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/ng.2844","article-title":"EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension","volume":"46","author":"Eyries","year":"2014","journal-title":"Nat Genet"},{"key":"10.1016\/j.jacc.2015.03.540_bib30","doi-asserted-by":"crossref","first-page":"D100","DOI":"10.1016\/j.jacc.2013.10.033","article-title":"Pulmonary hypertension due to left heart diseases","volume":"62","author":"Vachiery","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib31","doi-asserted-by":"crossref","first-page":"25S","DOI":"10.1016\/j.jacc.2004.02.033","article-title":"Pathologic assessment of vasculopathies in pulmonary hypertension","volume":"43","author":"Pietra","year":"2004","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib32","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.1016\/j.jacc.2004.02.029","article-title":"Cellular and molecular pathobiology of pulmonary arterial hypertension","volume":"43 12 Suppl S","author":"Humbert","year":"2004","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib33","doi-asserted-by":"crossref","first-page":"D4","DOI":"10.1016\/j.jacc.2013.10.025","article-title":"Relevant issues in the pathology and pathobiology of pulmonary hypertension","volume":"62","author":"Tuder","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/CIRCRESAHA.113.301141","article-title":"Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension","volume":"115","author":"Rabinovitch","year":"2014","journal-title":"Circ Res"},{"key":"10.1016\/j.jacc.2015.03.540_bib35","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1161\/CIRCULATIONAHA.113.004555","article-title":"Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay","volume":"129","author":"Huertas","year":"2014","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib36","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1183\/09031936.00151313","article-title":"Proinflammatory cytokine levels are linked to death in pulmonary arterial hypertension","volume":"43","author":"Cracowski","year":"2014","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib37","doi-asserted-by":"crossref","first-page":"D13","DOI":"10.1016\/j.jacc.2013.10.035","article-title":"Genetics and genomics of pulmonary arterial hypertension","volume":"62","author":"Soubrier","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib38","doi-asserted-by":"crossref","first-page":"499","DOI":"10.7326\/0003-4819-105-4-499","article-title":"Primary pulmonary hypertension: radiographic and scintigraphic patterns of histologic subtypes","volume":"105","author":"Rich","year":"1986","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1161\/CIRCULATIONAHA.109.911818","article-title":"Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era","volume":"122","author":"Humbert","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib40","doi-asserted-by":"crossref","DOI":"10.1183\/09031936.00004414","article-title":"Validation of two predictive models for survival in pulmonary arterial hypertension","author":"Sitbon","year":"2015","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib41","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.echo.2010.05.010","volume":"23","author":"Rudski","year":"2010","journal-title":"J\u00a0Am Soc Echocardiogr"},{"key":"10.1016\/j.jacc.2015.03.540_bib42","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/j.jacc.2006.07.061","article-title":"Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers","volume":"48","author":"Hoeper","year":"2006","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib43","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1161\/CIRCULATIONAHA.104.488486","article-title":"Long-term response to calcium channel blockers in idiopathic\u00a0pulmonary arterial hypertension","volume":"111","author":"Sitbon","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib44","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1161\/CIRCHEARTFAILURE.109.930701","article-title":"Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction","volume":"3","author":"Borlaug","year":"2010","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.jacc.2015.03.540_bib45","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1161\/CIRCHEARTFAILURE.110.958801","article-title":"Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction","volume":"4","author":"Thenappan","year":"2011","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.jacc.2015.03.540_bib46","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.echo.2007.10.003","article-title":"Noninvasive differentiation of pulmonary arterial and venous hypertension using conventional and Doppler tissue imaging echocardiography","volume":"21","author":"Willens","year":"2008","journal-title":"J\u00a0Am Soc Echocardiogr"},{"key":"10.1016\/j.jacc.2015.03.540_bib47","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.jcmg.2013.05.014","article-title":"LA volume by CMR distinguishes idiopathic from pulmonary hypertension due to HFpEF","volume":"6","author":"Crawley","year":"2013","journal-title":"J\u00a0Am Coll Cardiol Img"},{"key":"10.1016\/j.jacc.2015.03.540_bib48","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1161\/CIRCULATIONAHA.106.618397","article-title":"Exercise and respiratory training improve exercise\u00a0capacity and quality of life in patients with severe\u00a0chronic pulmonary hypertension","volume":"114","author":"Mereles","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib49","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1056\/NEJM199207093270203","article-title":"The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension","volume":"327","author":"Rich","year":"1992","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib50","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1378\/chest.112.3.714","article-title":"The effect of anticoagulant therapy in primary and anorectic drug-induced pulmonary hypertension","volume":"112","author":"Frank","year":"1997","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib51","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1161\/01.CIR.70.4.580","article-title":"Primary pulmonary hypertension: natural history and the importance of thrombosis","volume":"70","author":"Fuster","year":"1984","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib52","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1161\/CIRCULATIONAHA.113.004526","article-title":"Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)","volume":"129","author":"Olsson","year":"2014","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib53","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1164\/ajrccm.159.6.9804054","article-title":"Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension","volume":"159","author":"Tuder","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib54","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1056\/NEJM199602013340504","article-title":"A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension","volume":"334","author":"Barst","year":"1996","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib55","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/01.CIR.0000029100.82385.58","article-title":"Survival in primary pulmonary hypertension: the impact of epoprostenol therapy","volume":"106","author":"McLaughlin","year":"2002","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib56","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/S0735-1097(02)02012-0","article-title":"Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival","volume":"40","author":"Sitbon","year":"2002","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib57","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":"10.1016\/j.jacc.2015.03.540_bib58","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1164\/ajrccm.165.6.2106079","article-title":"Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial","volume":"165","author":"Simonneau","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib59","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.jacc.2010.01.027","article-title":"Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial","volume":"55","author":"McLaughlin","year":"2010","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib60","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1161\/CIRCULATIONAHA.112.124388","article-title":"Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial","volume":"127","author":"Jing","year":"2013","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib61","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1378\/chest.11-2212","article-title":"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","volume":"142","author":"Tapson","year":"2012","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib62","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1378\/chest.12-2875","article-title":"Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial","volume":"144","author":"Tapson","year":"2013","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib63","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1056\/NEJMoa020204","article-title":"Inhaled iloprost for severe pulmonary hypertension","volume":"347","author":"Olschewski","year":"2002","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib64","doi-asserted-by":"crossref","first-page":"464","DOI":"10.7326\/0003-4819-114-6-464","article-title":"Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease?","volume":"114","author":"Stewart","year":"1991","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib65","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJM199306173282402","article-title":"Expression of endothelin-1 in the lungs of patients with pulmonary hypertension","volume":"328","author":"Giaid","year":"1993","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib66","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1378\/chest.06-0682","article-title":"Endothelin-1\/endothelin-3 ratio: a potential prognostic factor of pulmonary arterial hypertension","volume":"131","author":"Montani","year":"2007","journal-title":"Chest"},{"key":"10.1016\/j.jacc.2015.03.540_bib67","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","article-title":"Bosentan therapy for pulmonary arterial hypertension","volume":"346","author":"Rubin","year":"2002","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib68","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1016\/S0140-6736(08)60919-8","article-title":"Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial","volume":"371","author":"Galie","year":"2008","journal-title":"Lancet"},{"key":"10.1016\/j.jacc.2015.03.540_bib69","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/CIRCULATIONAHA.106.630715","article-title":"Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study","volume":"114","author":"Galie","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib70","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","article-title":"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","volume":"117","author":"Galie","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib71","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-3-662-45805-1_9","article-title":"Endothelin receptor antagonists","volume":"218","author":"Clozel","year":"2013","journal-title":"Handb Exp Pharmacol"},{"key":"10.1016\/j.jacc.2015.03.540_bib72","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1213917","article-title":"Macitentan and morbidity and mortality in pulmonary arterial hypertension","volume":"369","author":"Pulido","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib73","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1056\/NEJM199507273330403","article-title":"Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension","volume":"333","author":"Giaid","year":"1995","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib74","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1056\/NEJMoa050010","article-title":"Sildenafil citrate therapy for pulmonary arterial hypertension","volume":"353","author":"Galie","year":"2005","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib75","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1161\/CIRCULATIONAHA.108.839274","article-title":"Tadalafil therapy for pulmonary arterial hypertension","volume":"119","author":"Galie","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib76","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1183\/09031936.00039808","article-title":"First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension","volume":"33","author":"Grimminger","year":"2009","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib77","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1161\/CIRCULATIONAHA.110.981738","article-title":"Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease","volume":"123","author":"Stasch","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib78","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa1209657","article-title":"Riociguat for the treatment of chronic thromboembolic pulmonary hypertension","volume":"369","author":"Ghofrani","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib79","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1056\/NEJMoa1209655","article-title":"Riociguat for the treatment of pulmonary arterial hypertension","volume":"369","author":"Ghofrani","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib80","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1164\/rccm.201104-0662CI","article-title":"Intensive care unit management of patients with severe pulmonary hypertension and right heart failure","volume":"184","author":"Hoeper","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib81","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ejcts.2010.02.039","article-title":"Long-term outcome of double-lung and heart-lung transplantation for pulmonary hypertension: a comparative retrospective study of 219 patients","volume":"38","author":"Fadel","year":"2010","journal-title":"Eur J Cardiothorac Surg"},{"key":"10.1016\/j.jacc.2015.03.540_bib82","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1055\/s-0033-1356460","article-title":"Management of severe pulmonary arterial hypertension","volume":"34","author":"Granton","year":"2013","journal-title":"Semin Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib83","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1161\/CIRCULATIONAHA.114.006974","article-title":"Advances in therapeutic interventions for patients with pulmonary arterial hypertension","volume":"130","author":"Humbert","year":"2014","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib84","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1183\/09031936.00072210","article-title":"Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension","volume":"38","author":"Sandoval","year":"2011","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib85","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1183\/09031936.00116313","article-title":"Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study","volume":"43","author":"Sitbon","year":"2014","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib86","doi-asserted-by":"crossref","first-page":"D73","DOI":"10.1016\/j.jacc.2013.10.034","article-title":"Treatment goals of pulmonary hypertension","volume":"62","author":"McLaughlin","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib87","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1378\/chest.14-0793","article-title":"Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report","volume":"146","author":"Taichman","year":"2014","journal-title":"Chest"},{"issue":"Suppl D","key":"10.1016\/j.jacc.2015.03.540_bib88","doi-asserted-by":"crossref","first-page":"D1","DOI":"10.1016\/j.jacc.2013.10.030","article-title":"The Fifth World Symposium on Pulmonary Hypertension","volume":"62","author":"Galie","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib89","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1183\/09031936.00137511","article-title":"Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension","volume":"40","author":"Simonneau","year":"2012","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib90","unstructured":"McLaughlin VV. Effect of selexipag on morbidity\/mortality in pulmonary arterial hyertension: results of the GRIPHON study. Paper presented at: ACC.15; March 15, 2015; San Diego, CA."},{"key":"10.1016\/j.jacc.2015.03.540_bib91","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1161\/CIRCULATIONAHA.112.000765","article-title":"Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study","volume":"127","author":"Hoeper","year":"2013","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib92","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1161\/CIRCULATIONAHA.105.591321","article-title":"Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: critical role for serotonin-induced smooth muscle hyperplasia","volume":"113","author":"Eddahibi","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib93","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1253\/circj.CJ-13-0443","article-title":"Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension","volume":"77","author":"Fukumoto","year":"2013","journal-title":"Circ J"},{"key":"10.1016\/j.jacc.2015.03.540_bib94","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/art.23303","article-title":"Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases","volume":"58","author":"Jais","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jacc.2015.03.540_bib95","unstructured":"ClinicalTrials.gov. Rituximab for treatment of\u00a0systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). 2014. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01086540. Accessed March 15,\u00a02015."},{"key":"10.1016\/j.jacc.2015.03.540_bib96","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1161\/hc0202.101974","article-title":"Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels","volume":"105","author":"Michelakis","year":"2002","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2015.03.540_bib97","unstructured":"ClinicalTrials.gov. Dichloroacetate (DCA) for the treatment of pulmonary arterial hypertension. 2014. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01083524. Accessed March 15,\u00a02015."},{"key":"10.1016\/j.jacc.2015.03.540_bib98","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1172\/JCI65592","article-title":"FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension","volume":"123","author":"Spiekerkoetter","year":"2013","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jacc.2015.03.540_bib99","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.jacc.2006.12.037","article-title":"Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial","volume":"49","author":"Wang","year":"2007","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib100","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1164\/rccm.201203-0411OC","article-title":"Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension","volume":"186","author":"de Man","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib101","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1164\/rccm.201003-0335OC","article-title":"Adrenergic receptor blockade reverses right heart\u00a0remodeling and dysfunction in pulmonary hypertensive rats","volume":"182","author":"Bogaard","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib102","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.jacc.2013.05.075","article-title":"Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension)","volume":"62","author":"Chen","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib103","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1093\/ejcts\/ezu445","article-title":"Palliative Potts shunt for the treatment of children with drug-refractory pulmonary arterial hypertension: updated data from the first 24 patients","volume":"47","author":"Baruteau","year":"2015","journal-title":"Eur J Cardiothorac Surg"},{"key":"10.1016\/j.jacc.2015.03.540_bib104","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.healun.2013.01.1049","article-title":"Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: initial clinical experience","volume":"32","author":"Esch","year":"2013","journal-title":"J\u00a0Heart Lung Transplant"},{"key":"10.1016\/j.jacc.2015.03.540_bib105","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1183\/09031936.00089212","article-title":"Outcomes of noncardiac, nonobstetric surgery in patients with PAH: an international prospective survey","volume":"41","author":"Meyer","year":"2013","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib106","doi-asserted-by":"crossref","first-page":"709407","DOI":"10.1155\/2012\/709407","article-title":"Pulmonary hypertension in pregnancy: critical care management","volume":"2012","author":"Bassily-Marcus","year":"2012","journal-title":"Pulmonary Med"},{"key":"10.1016\/j.jacc.2015.03.540_bib107","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1097\/00000542-200506000-00012","article-title":"Severe pulmonary hypertension during pregnancy","volume":"102","author":"Bonnin","year":"2005","journal-title":"Anesthesiology"},{"key":"10.1016\/j.jacc.2015.03.540_bib108","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1183\/09031936.00141211","article-title":"Pregnancy outcomes in pulmonary arterial hypertension in the modern management era","volume":"40","author":"Jais","year":"2012","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jacc.2015.03.540_bib109","first-page":"E226","article-title":"Use of Tandem Heart as a temporary hemodynamic support option for severe pulmonary artery hypertension complicated by cardiogenic shock","volume":"19","author":"Rajdev","year":"2007","journal-title":"J\u00a0Invasive Cardiol"},{"key":"10.1016\/j.jacc.2015.03.540_bib110","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/j.athoracsur.2012.10.013","article-title":"Use of the Impella 2.5 Microaxial pump for right ventricular support after insertion of Heartmate II left ventricular assist device","volume":"95","author":"Anderson","year":"2013","journal-title":"Ann Thorac Surg"},{"key":"10.1016\/j.jacc.2015.03.540_bib111","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1001\/jamainternmed.2013.319","article-title":"Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers: the multicenter RePHerral study","volume":"173","author":"Deano","year":"2013","journal-title":"JAMA Int Med"}],"container-title":["Journal of the American College of Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S073510971501623X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S073510971501623X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,2,10]],"date-time":"2019-02-10T03:03:35Z","timestamp":1549767815000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S073510971501623X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":111,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["S073510971501623X"],"URL":"https:\/\/doi.org\/10.1016\/j.jacc.2015.03.540","relation":{},"ISSN":["0735-1097"],"issn-type":[{"value":"0735-1097","type":"print"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Management of Pulmonary Arterial\u00a0Hypertension","name":"articletitle","label":"Article Title"},{"value":"Journal of the American College of Cardiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jacc.2015.03.540","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}