Download PDF
Semin Respir Crit Care Med 2017; 38(05): 596-605
DOI: 10.1055/s-0037-1606202
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Screening of Pulmonary Arterial Hypertension

Edmund M. T. Lau
1   Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney Medical School, University of Sydney, Camperdown, Australia
,
David S. Celermajer
2   Department of Cardiology, Royal Prince Alfred Hospital, Sydney Medical School, University of Sydney, Camperdown, Australia
,
Anne Keogh
3   Heart Transplant Unit, St Vincent's Hospital, Darlinghurst, Australia
4   St. Vincent's Clinical School, University of New South Wales, Darlinghurst, Australia
,
Vivek Thakkar
5   Department of Rheumatology, Liverpool Hospital, Sydney, New South Wales, Australia
6   School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
7   South Western Sydney Clinical School, University of New South Wales, Liverpool, Australia
8   Arthritis Research Unit of the Ingham Institute, Liverpool, Australia
› Author Affiliations
Further Information

Publication History

Publication Date:
15 October 2017 (online)

    Permissions and Reprints

Abstract

The majority of patients with pulmonary arterial hypertension (PAH) present in advanced stages of the disease, when therapeutic interventions may potentially be less effective. Early diagnosis is associated with improved outcomes, supporting best practice recommendations that asymptomatic patients in high-risk populations such as systemic sclerosis or carriers of a PAH-causing mutation should be offered periodic screening for PAH. An evidence-based algorithm for screening systemic sclerosis-associated PAH is now available based on the DETECT study. A multimodal approach using Doppler echocardiography, lung function testing, and B-type natriuretic peptides improves screening accuracy but at the expense of higher health care costs. Patients with abnormal hemodynamics but who do not meet definition for diagnosis of pulmonary hypertension (such as mean pulmonary artery pressure between 21 and 24 mm Hg) should be closely followed up given their increased risk of progression to PAH. This review summarizes the current approach to screening for PAH and discusses areas of uncertainties that require further research.

Keywords

pulmonary arterial hypertension - systemic sclerosis - screening - early detection
 

  • References

  • 1 Humbert M, Lau EM, Montani D, Jaïs X, Sitbon O, Simonneau G. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation 2014; 130 (24) 2189-2208
    CrossrefPubMedGoogle Scholar
  • 2 Hoeper MM, Bogaard HJ, Condliffe R. , et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 2013; 62 (25, Suppl): D42-D50
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Simonneau G, Gatzoulis MA, Adatia I. , et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62 (25, Suppl): D34-D41
    CrossrefPubMedGoogle Scholar
  • 5 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
    CrossrefPubMedGoogle Scholar
  • 6 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
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Farber HW, Miller DP, Poms AD. , et al. Five-year outcomes of patients enrolled in the REVEAL Registry. Chest 2015; 148 (04) 1043-1054
    CrossrefPubMedGoogle Scholar
  • 11 Lefèvre 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 (09) 2412-2423
    CrossrefPubMedGoogle Scholar
  • 12 Launay D, Sitbon O, Hachulla E. , et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. Ann Rheum Dis 2013; 72 (12) 1940-1946
    CrossrefPubMedGoogle Scholar
  • 13 Chung L, Liu J, Parsons L. , et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest 2010; 138 (06) 1383-1394
    CrossrefPubMedGoogle Scholar
  • 14 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 (03) 489-495
    CrossrefPubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 Lau EM, Humbert M, Celermajer DS. Early detection of pulmonary arterial hypertension. Nat Rev Cardiol 2015; 12 (03) 143-155
    CrossrefPubMedGoogle Scholar
  • 17 Lau EM, Manes A, Celermajer DS, Galiè N. Early detection of pulmonary vascular disease in pulmonary arterial hypertension: time to move forward. Eur Heart J 2011; 32 (20) 2489-2498
    CrossrefPubMedGoogle Scholar
  • 18 Strange G, Gabbay E, Kermeen F. , et al. Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: the delay study. Pulm Circ 2013; 3 (01) 89-94
    CrossrefPubMedGoogle Scholar
  • 19 Badesch DB, Raskob GE, Elliott CG. , et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010; 137 (02) 376-387
    CrossrefPubMedGoogle Scholar
  • 20 Condliffe R, Kiely DG, Peacock AJ. , et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 2009; 179 (02) 151-157
    CrossrefPubMedGoogle Scholar
  • 21 Humbert M, Yaici A, de Groote P. , et al. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. Arthritis Rheum 2011; 63 (11) 3522-3530
    CrossrefPubMedGoogle Scholar
  • 22 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
    CrossrefPubMedGoogle Scholar
  • 23 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
    CrossrefPubMedGoogle Scholar
  • 24 Machado RD, Aldred MA, James V. , et al. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat 2006; 27 (02) 121-132
    CrossrefPubMedGoogle Scholar
  • 25 Mukerjee D, St George D, Coleiro B. , et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 2003; 62 (11) 1088-1093
    CrossrefPubMedGoogle Scholar
  • 26 Hachulla E, Gressin V, Guillevin L. , et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum 2005; 52 (12) 3792-3800
    CrossrefPubMedGoogle Scholar
  • 27 Vonk MC, Broers B, Heijdra YF. , et al. Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study. Ann Rheum Dis 2009; 68 (06) 961-965
    CrossrefPubMedGoogle Scholar
  • 28 Phung S, Strange G, Chung LP. , et al. Prevalence of pulmonary arterial hypertension in an Australian scleroderma population: screening allows for earlier diagnosis. Intern Med J 2009; 39 (10) 682-691
    CrossrefPubMedGoogle Scholar
  • 29 Larkin EK, Newman JH, Austin ED. , et al. Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 2012; 186 (09) 892-896
    CrossrefPubMedGoogle Scholar
  • 30 Coghlan JG, Denton CP, Grünig E. , et al; DETECT Study Group. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 2014; 73 (07) 1340-1349
    CrossrefPubMedGoogle Scholar
  • 31 Prabu A, Patel K, Yee CS. , et al. Prevalence and risk factors for pulmonary arterial hypertension in patients with lupus. Rheumatology (Oxford) 2009; 48 (12) 1506-1511
    CrossrefPubMedGoogle Scholar
  • 32 Pan TL, Thumboo J, Boey ML. Primary and secondary pulmonary hypertension in systemic lupus erythematosus. Lupus 2000; 9 (05) 338-342
    CrossrefPubMedGoogle Scholar
  • 33 Hadengue A, Benhayoun MK, Lebrec D, Benhamou JP. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991; 100 (02) 520-528
    CrossrefPubMedGoogle Scholar
  • 34 Colle IO, Moreau R, Godinho E. , et al. Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study. Hepatology 2003; 37 (02) 401-409
    CrossrefPubMedGoogle Scholar
  • 35 Swanson KL, Wiesner RH, Nyberg SL, Rosen CB, Krowka MJ. Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. Am J Transplant 2008; 8 (11) 2445-2453
    CrossrefPubMedGoogle Scholar
  • 36 European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL Clinical Practice Guidelines: liver transplantation. J Hepatol 2016; 64 (02) 433-485
    CrossrefPubMedGoogle Scholar
  • 37 van Riel AC, Schuuring MJ, van Hessen ID. , et al. Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification. Int J Cardiol 2014; 174 (02) 299-305
    CrossrefPubMedGoogle Scholar
  • 38 Engelfriet PM, Duffels MG, Möller T. , et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart 2007; 93 (06) 682-687
    CrossrefPubMedGoogle Scholar
  • 39 Sitbon O, Lascoux-Combe C, Delfraissy JF. , et al. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med 2008; 177 (01) 108-113
    CrossrefPubMedGoogle Scholar
  • 40 Fisher MR, Forfia PR, Chamera E. , et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med 2009; 179 (07) 615-621
    CrossrefPubMedGoogle Scholar
  • 41 D'Alto M, Romeo E, Argiento P. , et al. Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension. Int J Cardiol 2013; 168 (04) 4058-4062
    CrossrefPubMedGoogle Scholar
  • 42 Steen V, Medsger Jr TA. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum 2003; 48 (02) 516-522
    CrossrefPubMedGoogle Scholar
  • 43 Trip P, Girerd B, Bogaard HJ. , et al. Diffusion capacity and BMPR2 mutations in pulmonary arterial hypertension. Eur Respir J 2014; 43 (04) 1195-1198
    CrossrefPubMedGoogle Scholar
  • 44 Williams MH, Handler CE, Akram R. , et al. Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur Heart J 2006; 27 (12) 1485-1494
    CrossrefPubMedGoogle Scholar
  • 45 Mukerjee D, Yap LB, Holmes AM. , et al. Significance of plasma N-terminal pro-brain natriuretic peptide in patients with systemic sclerosis-related pulmonary arterial hypertension. Respir Med 2003; 97 (11) 1230-1236
    CrossrefPubMedGoogle Scholar
  • 46 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 (03) R143
    CrossrefPubMedGoogle Scholar
  • 47 Thakkar V, Stevens W, Prior D. , et al. The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study. Arthritis Res Ther 2013; 15 (06) R193
    CrossrefPubMedGoogle Scholar
  • 48 Thakkar V, Stevens WM, Moore OA, Nikpour M. Performance of screening algorithms in systemic sclerosis-related pulmonary arterial hypertension: a systematic review. Intern Med J 2013; 43 (07) 751-760
    CrossrefPubMedGoogle Scholar
  • 49 Hao Y, Thakkar V, Stevens W. , et al. A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis. Arthritis Res Ther 2015; 17: 7
    CrossrefPubMedGoogle Scholar
  • 50 Hachulla E, de Groote P, Gressin V. , et al; Itinér AIR-Sclérodermie Study Group. The three-year incidence of pulmonary arterial hypertension associated with systemic sclerosis in a multicenter nationwide longitudinal study in France. Arthritis Rheum 2009; 60 (06) 1831-1839
    CrossrefPubMedGoogle Scholar
  • 51 Morrisroe K, Stevens W, Sahhar J, Rabusa C, Nikpour M, Proudman S. ; Australian Scleroderma Interest Group (ASIG). Epidemiology and disease characteristics of systemic sclerosis-related pulmonary arterial hypertension: results from a real-life screening programme. Arthritis Res Ther 2017; 19 (01) 42
    CrossrefPubMedGoogle Scholar
  • 52 Valerio CJ, Schreiber BE, Handler CE, Denton CP, Coghlan JG. Borderline mean pulmonary artery pressure in patients with systemic sclerosis: transpulmonary gradient predicts risk of developing pulmonary hypertension. Arthritis Rheum 2013; 65 (04) 1074-1084
    CrossrefPubMedGoogle Scholar
  • 53 Herve P, Lau EM, Sitbon O. , et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J 2015; 46 (03) 728-737
    CrossrefPubMedGoogle Scholar
  • 54 Naeije R, Vanderpool R, Dhakal BP. , et al. Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. Am J Respir Crit Care Med 2013; 187 (06) 576-583
    CrossrefPubMedGoogle Scholar
  • 55 Godinas L, Lau EM, Chemla D. , et al. Diagnostic concordance of different criteria for exercise pulmonary hypertension in subjects with normal resting pulmonary artery pressure. Eur Respir J 2016; 48 (01) 254-257
    CrossrefPubMedGoogle Scholar
  • 56 Lau EM, Thakkar V, Humbert M, Herve P. To stress or not to stress? Exercise pulmonary haemodynamic testing in systemic sclerosis. Eur Respir J 2016; 48 (06) 1549-1552
    CrossrefPubMedGoogle Scholar
  • 57 Lau EM, Chemla D, Whyte K, Kovacs G, Olschewski H, Herve P. Does exercise pulmonary hypertension exist?. Curr Opin Pulm Med 2016; 22 (05) 400-407
    PubMedGoogle Scholar
  • 58 Lau EM, Godinas L, Sitbon O. , et al. Resting pulmonary artery pressure of 21-24 mmHg predicts abnormal exercise haemodynamics. Eur Respir J 2016; 47 (05) 1436-1444
    CrossrefPubMedGoogle Scholar
  • 59 Stamm A, Saxer S, Lichtblau M. , et al. Exercise pulmonary haemodynamics predict outcome in patients with systemic sclerosis. Eur Respir J 2016; 48 (06) 1658-1667
    CrossrefPubMedGoogle Scholar
  • 60 Saggar R, Khanna D, Shapiro S. , et al. Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. Arthritis Rheum 2012; 64 (12) 4072-4077
    CrossrefPubMedGoogle Scholar
  • 61 Kovacs G, Maier R, Aberer E. , et al. Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure. Arthritis Rheum 2012; 64 (04) 1257-1262
    CrossrefPubMedGoogle Scholar
  • 62 Quinlivan A, Thakkar V, Stevens W. , et al. Cost savings with a new screening algorithm for pulmonary arterial hypertension in systemic sclerosis. Intern Med J 2015; 45 (11) 1134-1140
    CrossrefPubMedGoogle Scholar