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Semin Respir Crit Care Med 2017; 38(05): 606-618
DOI: 10.1055/s-0037-1606317
DOI: 10.1055/s-0037-1606317
Review Article
Idiopathic Pulmonary Arterial Hypertension: Evolving Therapeutic Strategies
Further Information
Publication History
Publication Date:
15 October 2017 (online)
Abstract
The field of pulmonary arterial hypertension (PAH) has seen substantial changes in the epidemiology, associated comorbidities, treatment algorithms, and prognosis in the past decade. Specifically for idiopathic PAH (IPAH), there has been a noted increase in the age of initial diagnosis. Increasing focus is being placed on appropriate categorization of patients with PAH, both in terms of diagnosis and individualized risk stratification. This is especially relevant given that patients being diagnosed with incident IPAH are now older and with multiple comorbidities, putting them at a higher risk of being mislabeled as PAH. The biggest impact has been seen in the number of pharmaceutical options available for these patients, resulting in improvement in both short- and long-term outcomes. In addition, there has been a shift in the treatment approach to the early use of combination therapies in PAH, since it has been demonstrated to improve clinical outcomes. Novel therapies are in the pipeline for patients with IPAH to impact both the morbidity and mortality of this deadly disease.
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References
- 1 Galiè 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 (01) 67-119
- 2 Simonneau G, Gatzoulis MA, Adatia I. , et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62 (25, Suppl): D34-D41
- 3 Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. Eur Respir J 2007; 30 (01) 104-109
- 4 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 (09) 1023-1030
- 5 Ling Y, Johnson MK, Kiely DG. , et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med 2012; 186 (08) 790-796
- 6 Moledina S, Hislop AA, Foster H, Schulze-Neick I, Haworth SG. Childhood idiopathic pulmonary arterial hypertension: a national cohort study. Heart 2010; 96 (17) 1401-1406
- 7 Badesch DB, Raskob GE, Elliott CG. , et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. Chest 2010; 137 (02) 376-387
- 8 Rich S, Dantzker DR, Ayres SM. , et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987; 107 (02) 216-223
- 9 McGoon MD, Benza RL, Escribano-Subias P. , et al. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol 2013; 62 (25, Suppl): D51-D59
- 10 Humbert M, Sitbon O, Chaouat A. , et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122 (02) 156-163
- 11 Hoeper MM, Huscher D, Ghofrani HA. , et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol 2013; 168 (02) 871-880
- 12 Poms AD, Turner M, Farber HW, Meltzer LA, McGoon MD. Comorbid conditions and outcomes in patients with pulmonary arterial hypertension: a REVEAL registry analysis. Chest 2013; 144 (01) 169-176
- 13 Dorfmüller P, Humbert M. Progress in pulmonary arterial hypertension pathology: relighting a torch inside the tunnel. Am J Respir Crit Care Med 2012; 186 (03) 210-212
- 14 Dai Z, Zhao YY. Discovery of a murine model of clinical PAH: mission impossible?. Trends Cardiovasc Med 2017; 27 (04) 229-236
- 15 Ryan JJ, Marsboom G, Archer SL. Rodent models of group 1 pulmonary hypertension. Handb Exp Pharmacol 2013; 218: 105-149
- 16 Galiè N, Barberà JA, Frost AE. , et al; AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med 2015; 373 (09) 834-844
- 17 Rothman A, Mann DM, House MT. , et al. Transvenous procurement of pulmonary artery smooth muscle and endothelial cells using a novel endoarterial biopsy catheter in a canine model. J Am Coll Cardiol 1996; 27 (01) 218-224
- 18 Sa S, Gu M, Chapperll J. , et al. Induced pluripotent stem cell model of pulmonary arterial hypertension reveals novel gene expression and patient specificity. Am J Respir Crit Care Me 2017; 195 (07) 930-941
- 19 Benza RL, Williams G, Wu C. , et al. In situ expression of Bcl-2 in pulmonary artery endothelial cells associates with pulmonary arterial hypertension relative to heart failure with preserved ejection fraction. Pulm Circ 2016; 6 (04) 551-556
- 20 Tuder RM, Archer SL, Dorfmüller P. , et al. Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol 2013; 62 (25, Suppl): D4-D12
- 21 Lane KB, Machado RD, Pauciulo MW. , et al; International PPH Consortium. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 2000; 26 (01) 81-84
- 22 Deng Z, Morse JH, Slager SL. , et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 2000; 67 (03) 737-744
- 23 Atkinson C, Stewart S, Upton PD. , et al. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 2002; 105 (14) 1672-1678
- 24 Austin ED, Cogan JD, West JD. , et al. Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females. Eur Respir J 2009; 34 (05) 1093-1099
- 25 Austin ED, Hamid R, Hemnes AR. , et al. BMPR2 expression is suppressed by signaling through the estrogen receptor. Biol Sex Differ 2012; 3 (01) 6
- 26 Ventetuolo CE, Mitra N, Wan F. , et al. Oestradiol metabolism and androgen receptor genotypes are associated with right ventricular function. Eur Respir J 2016; 47 (02) 553-563
- 27 Galiè 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 Respir J 2015; 46 (04) 903-975
- 28 McLaughlin VV, Archer SL, Badesch DB. , et al; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. 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 developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 2009; 53 (17) 1573-1619
- 29 Bossone E, D'Andrea A, D'Alto M. , et al. Echocardiography in pulmonary arterial hypertension: from diagnosis to prognosis. J Am Soc Echocardiogr 2013; 26 (01) 1-14
- 30 Melenovsky V, Borlaug BA, Rosen B. , et al. Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction. J Am Coll Cardiol 2007; 49 (02) 198-207
- 31 Nagueh SF, Appleton CP, Gillebert TC. , et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009; 10 (02) 165-193
- 32 Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol 2002; 90 (12) 1284-1289
- 33 Caballero L, Kou S, Dulgheru R. , et al. Echocardiographic reference ranges for normal cardiac Doppler data: results from the NORRE study. Eur Heart J Cardiovasc Imaging 2015; 16 (09) 1031-1041
- 34 Nagueh SF, Smiseth OA, Appleton CP. , et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2016; 17 (12) 1321-1360
- 35 Arkles JS, Opotowsky AR, Ojeda J. , et al. Shape of the right ventricular Doppler envelope predicts hemodynamics and right heart function in pulmonary hypertension. Am J Respir Crit Care Med 2011; 183 (02) 268-276
- 36 Opotowsky AR, Ojeda J, Rogers F. , et al. A simple echocardiographic prediction rule for hemodynamics in pulmonary hypertension. Circ Cardiovasc Imaging 2012; 5 (06) 765-775
- 37 Tossavainen E, Söderberg S, Grönlund C, Gonzalez M, Henein MY, Lindqvist P. Pulmonary artery acceleration time in identifying pulmonary hypertension patients with raised pulmonary vascular resistance. Eur Heart J Cardiovasc Imaging 2013; 14 (09) 890-897
- 38 Abbas AE, Franey LM, Marwick T. , et al. Noninvasive assessment of pulmonary vascular resistance by Doppler echocardiography. J Am Soc Echocardiogr 2013; 26 (10) 1170-1177
- 39 Dahiya A, Vollbon W, Jellis C, Prior D, Wahi S, Marwick T. Echocardiographic assessment of raised pulmonary vascular resistance: application to diagnosis and follow-up of pulmonary hypertension. Heart 2010; 96 (24) 2005-2009
- 40 Opotowsky AR, Clair M, Afilalo J. , et al. A simple echocardiographic method to estimate pulmonary vascular resistance. Am J Cardiol 2013; 112 (06) 873-882
- 41 Dadfarmay S, Berkowitz R, Kim B, Manchikalapudi RB. Differentiating pulmonary arterial and pulmonary venous hypertension and the implications for therapy. Congest Heart Fail 2010; 16 (06) 287-291
- 42 Zakir RM, Al-Dehneh A, Maher J, Saric M, Berkowitz RL. Right ventricular failure in patients with preserved ejection fraction and diastolic dysfunction: an underrecognized clinical entity. Congest Heart Fail 2007; 13 (03) 164-169
- 43 van de Veerdonk MC, Kind T, Marcus JT. , et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 2011; 58 (24) 2511-2519
- 44 Brewis MJ, Bellofiore A, Vanderpool RR. , et al. Imaging right ventricular function to predict outcome in pulmonary arterial hypertension. Int J Cardiol 2016; 218: 206-211
- 45 Sanz J, García-Alvarez A, Fernández-Friera L. , et al. Right ventriculo-arterial coupling in pulmonary hypertension: a magnetic resonance study. Heart 2012; 98 (03) 238-243
- 46 Truong U, Patel S, Kheyfets V. , et al. Non-invasive determination by cardiovascular magnetic resonance of right ventricular-vascular coupling in children and adolescents with pulmonary hypertension. J Cardiovasc Magn Reson 2015; 17: 81
- 47 Blyth KG, Groenning BA, Martin TN. , et al. Contrast enhanced-cardiovascular magnetic resonance imaging in patients with pulmonary hypertension. Eur Heart J 2005; 26 (19) 1993-1999
- 48 McCann GP, Beek AM, Vonk-Noordegraaf A, van Rossum AC. Delayed contrast-enhanced magnetic resonance imaging in pulmonary arterial hypertension. Circulation 2005; 112 (16) e268
- 49 Sanz J, Dellegrottaglie S, Kariisa M. , et al. Prevalence and correlates of septal delayed contrast enhancement in patients with pulmonary hypertension. Am J Cardiol 2007; 100 (04) 731-735
- 50 D'Alonzo GE, Barst RJ, Ayres SM. , et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115 (05) 343-349
- 51 Benza RL, Miller DP, Gomberg-Maitland M. , et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010; 122 (02) 164-172
- 52 Heresi GA, Tang WH, Aytekin M, Hammel J, Hazen SL, Dweik RA. Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial hypertension. Eur Respir J 2012; 39 (04) 939-944
- 53 Dhaun N, Vachiery JL, Benza RL. , et al. Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: clinical associations. J Heart Lung Transplant 2014; 33 (05) 521-527
- 54 Carlomagno G, Messalli G, Melillo RM. , et al. Serum soluble ST2 and interleukin-33 levels in patients with pulmonary arterial hypertension. Int J Cardiol 2013; 168 (02) 1545-1547
- 55 Zheng YG, Yang T, He JG. , et al. Plasma soluble ST2 levels correlate with disease severity and predict clinical worsening in patients with pulmonary arterial hypertension. Clin Cardiol 2014; 37 (06) 365-370
- 56 Fijalkowska A, Kurzyna M, Torbicki A. , et al. Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension. Chest 2006; 129 (05) 1313-1321
- 57 Mauritz GJ, Rizopoulos D, Groepenhoff H. , et al. Usefulness of serial N-terminal pro-B-type natriuretic peptide measurements for determining prognosis in patients with pulmonary arterial hypertension. Am J Cardiol 2011; 108 (11) 1645-1650
- 58 Nagaya N, Nishikimi T, Uematsu M. , et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 2000; 102 (08) 865-870
- 59 Kuhn KP, Byrne DW, Arbogast PG, Doyle TP, Loyd JE, Robbins IM. Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol. Am J Respir Crit Care Med 2003; 167 (04) 580-586
- 60 McLaughlin VV, Sitbon O, Badesch DB. , et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005; 25 (02) 244-249
- 61 Raymond RJ, Hinderliter AL, Willis PW. , et al. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 2002; 39 (07) 1214-1219
- 62 Forfia PR, Fisher MR, Mathai SC. , et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med 2006; 174 (09) 1034-1041
- 63 Badagliacca R, Papa S, Valli G. , et al. Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension. Chest 2016; 150 (06) 1313-1322
- 64 Courand PY, Pina Jomir G, Khouatra C. , et al. Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension. Eur Respir J 2015; 45 (01) 139-149
- 65 McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002; 106 (12) 1477-1482
- 66 Sitbon O, Humbert M, Nunes H. , et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002; 40 (04) 780-788
- 67 Benza RL, Gomberg-Maitland M, Miller DP. , et al. The REVEAL registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 2012; 141 (02) 354-362
- 68 Benza RL, Miller DP, Foreman AJ. , et al. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis. J Heart Lung Transplant 2015; 34 (03) 356-361
- 69 Kanwar MK, Thenappan T, Vachiéry JL. Update in treatment options in pulmonary hypertension. J Heart Lung Transplant 2016; 35 (06) 695-703
- 70 Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984; 70 (04) 580-587
- 71 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 (01) 57-65
- 72 Kawut SM, Bagiella E, Lederer DJ. , et al; ASA-STAT Study Group. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation 2011; 123 (25) 2985-2993
- 73 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 (02) 76-81
- 74 Sitbon O, Humbert M, Jaïs X. , et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 111 (23) 3105-3111
- 75 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 (09) 1111-1117
- 76 Galiè N, Olschewski H, Oudiz RJ. , et al; Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies (ARIES) Group. 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
- 77 Rubin LJ, Badesch DB, Barst RJ. , et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346 (12) 896-903
- 78 Humbert M, Barst RJ, Robbins IM. , et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004; 24 (03) 353-359
- 79 Galiè N, Rubin Lj, Hoeper M. , et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 2008; 371 (9630): 2093-2100
- 80 Hoeper MM, Faulenbach C, Golpon H, Winkler J, Welte T, Niedermeyer J. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J 2004; 24 (06) 1007-1010
- 81 Hoeper MM, Leuchte H, Halank M. , et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2006; 28 (04) 691-694
- 82 Provencher S, Sitbon O, Humbert M, Cabrol S, Jaïs X, Simonneau G. Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur Heart J 2006; 27 (05) 589-595
- 83 Pulido T, Adzerikho I, Channick RN. , et al; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013; 369 (09) 809-818
- 84 Jing ZC, Yu ZX, Shen JY. , et al; Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension (EVALUATION) Study Group. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med 2011; 183 (12) 1723-1729
- 85 Galiè N, Brundage BH, Ghofrani HA. , et al; Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group. Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009; 119 (22) 2894-2903
- 86 Galiè N, Ghofrani HA, Torbicki A. , et al; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353 (20) 2148-2157
- 87 Ghofrani HA, Galiè N, Grimminger F. , et al; PATENT-1 Study Group. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013; 369 (04) 330-340
- 88 Sitbon O, McLaughlin VV, Badesch DB. , et al. Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol. Thorax 2005; 60 (12) 1025-1030
- 89 Barst RJ, Rubin LJ, Long WA. , et al; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996; 334 (05) 296-301
- 90 Simonneau G, Barst RJ, Galie N. , et al; Treprostinil Study Group. 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 (06) 800-804
- 91 Sitbon O, Channick R, Chin KM. , et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2015; 373: 2522-2533
- 92 Toyoda Y, Thacker J, Santos R. , et al. Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension. Ann Thorac Surg 2008; 86 (04) 1116-1122
- 93 Sitbon O, Sattler C, Bertoletti L. , et al. Initial dual oral combination therapy in pulmonary arterial hypertension. Eur Respir J 2016; 47 (06) 1727-1736
- 94 Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL registry. Chest 2012; 142 (02) 448-456
- 95 Kawut SM, Taichman DB, Ahya VN. , et al. Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl 2005; 11 (09) 1107-1111
- 96 Rosenzweig EB, Morse JH, Knowles JA. , et al. Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant 2008; 27 (06) 668-674
- 97 Sztrymf B, Coulet F, Girerd B. , et al. Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med 2008; 177 (12) 1377-1383
- 98 Halliday SJ, Hemnes AR, Robbins IM. , et al. Prognostic value of acute vasodilator response in pulmonary arterial hypertension: beyond the “classic” responders. J Heart Lung Transplant 2015; 34 (03) 312-318
- 99 Sitbon O, Humbert M, Jagot JL. , et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J 1998; 12 (02) 265-270
- 100 Tonelli AR, Alnuaimat H, Mubarak K. Pulmonary vasodilator testing and use of calcium channel blockers in pulmonary arterial hypertension. Respir Med 2010; 104 (04) 481-496
- 101 Thenappan T, Shah SJ, Rich S, Tian L, Archer SL, Gomberg-Maitland M. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J 2010; 35 (05) 1079-1087
- 102 Frost AE, Badesch DB, Barst RJ. , et al. The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US Contemporary Registries. Chest 2011; 139 (01) 128-137
- 103 Escribano-Subias P, Blanco I, López-Meseguer M. , et al; REHAP investigators. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J 2012; 40 (03) 596-603
- 104 Jia WB, Jiang X, Zuo XR. , et al. [Clinical characteristics of 161 Chinese patients with idiopathic pulmonary arterial hypertension]. Zhonghua Xin Xue Guan Bing Za Zhi 2012; 40 (08) 652-656
- 105 Kane GC, Maradit-Kremers H, Slusser JP, Scott CG, Frantz RP, McGoon MD. Integration of clinical and hemodynamic parameters in the prediction of long-term survival in patients with pulmonary arterial hypertension. Chest 2011; 139 (06) 1285-1293