EXTENDED REPORT

Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach

D Mukerjee¹, D St George³, B Coleiro⁴, C Knight¹, C P Denton¹, J Davar², C M Black¹, J G Coghlan²

¹ Department of Rheumatology, Royal Free Hospital, Pond Street, London NW3 2QG, UK
² Department of Cardiology, Royal Free Hospital, Pond Street, London NW3 2QG, UK
³ Southampton General Hospital, Tremona Road, Shirley, Southampton SO16 6YD, UK
⁴ Department of Internal Medicine, St Lukes Hospital, Balkara, Malta

Correspondence to:
Correspondence to:
Professor C M Black, Centre for Rheumatology, Royal Free Hospital, Pond Street, London NW32QG. UK;
c.black{at}rfc.ucl.ac.uk

Objective: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort.

Methods: A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of >35 mm Hg, carbon monoxide transfer factor (TLCO) <50% predicted, or a precipitous fall in TLCO >20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice.

Results: The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure—raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n=40) and without (n=108) pulmonary fibrosis (p=0.3).

Conclusions: The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation.

Keywords: systemic sclerosis; pulmonary arterial hypertension; survival; iloprost

Abbreviations: CCB, calcium channel blocker; HRCT, high resolution computed tomography; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PASP, pulmonary artery systolic pressures, PFTs, pulmonary function tests; PPH, primary pulmonary hypertension; PVR, pulmonary artery vascular resistance; SSC, systemic sclerosis; TLCO-carbon monoxide transfer factor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Allanore, Y, Wahbi, K, Borderie, D, Weber, S, Kahan, A, Meune, C (2009). N-terminal pro-brain natriuretic peptide in systemic sclerosis: a new cornerstone of cardiovascular assessment?. Ann Rheum Dis 68: 1885-1889 [Abstract] [Full Text]  
• Hachulla, E., Launay, D., Mouthon, L., Sitbon, O., Berezne, A., Guillevin, L., Hatron, P.-Y., Simonneau, G., Clerson, P., Humbert, M., for the French PAH-SSc Network, (2009). Is Pulmonary Arterial Hypertension Really a Late Complication of Systemic Sclerosis?. Chest 136: 1211-1219 [Abstract] [Full Text]  
• Authors/Task Force Members, , Galie, N., Hoeper, M. M., Humbert, M., Torbicki, A., Vachiery, J.-L., Barbera, J. A., Beghetti, M., Corris, P., Gaine, S., Gibbs, J. S., Gomez-Sanchez, M. A., Jondeau, G., Klepetko, W., Opitz, C., Peacock, A., Rubin, L., Zellweger, M., Simonneau, G., ESC Committee for Practice Guidelines (CPG), , Vahanian, A., Auricchio, A., Bax, J., Ceconi, C., Dean, V., Filippatos, G., Funck-Brentano, C., Hobbs, R., Kearney, P., McDonagh, T., McGregor, K., Popescu, B. A., Reiner, Z., Sechtem, U., Sirnes, P. A., Tendera, M., Vardas, P., Widimsky, P., Document Reviewers, , Sechtem, U., Al Attar, N., Andreotti, F., Aschermann, M., Asteggiano, R., Benza, R., Berger, R., Bonnet, D., Delcroix, M., Howard, L., Kitsiou, A. N, Lang, I., Maggioni, A., Nielsen-Kudsk, J. E., Park, M., Perrone-Filardi, P., Price, S., Domenech, M. T. S., Vonk-Noordegraaf, A., Zamorano, J. L. (2009). Guidelines for the diagnosis and treatment of pulmonary hypertension: The 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 the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30: 2493-2537 [Full Text]  
• BADESCH, D. B., McGOON, M. D., BARST, R. J., TAPSON, V. F., RUBIN, L. J., WIGLEY, F. M., KRAL, K. M., RAPHIOU, I. H., CRATER, G. D. (2009). Longterm Survival Among Patients with Scleroderma-associated Pulmonary Arterial Hypertension Treated with Intravenous Epoprostenol. The Journal of Rheumatology 36: 2244-2249 [Abstract] [Full Text]  
• Vachiery, J-L., Coghlan, G. (2009). Screening for pulmonary arterial hypertension in systemic sclerosis. ERR 18: 162-169 [Abstract] [Full Text]  
• Hagger, D., Condliffe, R., Woodhouse, N., Elliot, C. A., Armstrong, I. J., Davies, C., Hill, C., Akil, M., Wild, J. M., Kiely, D. G. (2009). Ventricular mass index correlates with pulmonary artery pressure and predicts survival in suspected systemic sclerosis-associated pulmonary arterial hypertension. Rheumatology (Oxford) 48: 1137-1142 [Abstract] [Full Text]  
• Overbeek, M. J., Vonk, M. C., Boonstra, A., Voskuyl, A. E., Vonk-Noordegraaf, A., Smit, E. F., Dijkmans, B. A. C., Postmus, P. E., Mooi, W. J., Heijdra, Y., Grunberg, K. (2009). Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy. Eur Respir J 34: 371-379 [Abstract] [Full Text]  
• TERRIER, B., CHARBONNEAU, F., TOUZE, E., BEREZNE, A., PAGNOUX, C., SILVERA, S., MEDER, J.-F., GUILLEVIN, L., OPPENHEIM, C., MOUTHON, L. (2009). Cerebral Vasculopathy Is Associated with Severe Vascular Manifestations in Systemic Sclerosis. The Journal of Rheumatology 36: 1486-1494 [Abstract] [Full Text]  
• Simonneau, G., Robbins, I. M., Beghetti, M., Channick, R. N., Delcroix, M., Denton, C. P., Elliott, C. G., Gaine, S. P., Gladwin, M. T., Jing, Z.-C., Krowka, M. J., Langleben, D., Nakanishi, N., Souza, R. (2009). Updated clinical classification of pulmonary hypertension.. J Am Coll Cardiol 54: S43-S54 [Abstract] [Full Text]  
• Hisamori, S., Nagayama, S., Kita, S., Kawamura, J.-i., Yoshizawa, A., Sakai, Y. (2009). Rapid Progression of Submucosal Invasive Micropapillary Carcinoma of the Colon in Progressive Systemic Sclerosis: Report of a Case. Jpn J Clin Oncol 39: 399-405 [Abstract] [Full Text]  
• Vonk, M C, Broers, B, Heijdra, Y F, Ton, E, Snijder, R, van Dijk, A P J, van Laar, J M, Bootsma, H, van Hal, P T. W, van den Hoogen, F H J, van Daele, P L A (2009). Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study. Ann Rheum Dis 68: 961-965 [Abstract] [Full Text]  
• Matucci-Cerinic, M., Steen, V., Nash, P., Hachulla, E. (2009). The complexity of managing systemic sclerosis: screening and diagnosis. Rheumatology (Oxford) 48: iii8-iii13 [Abstract] [Full Text]  
• McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., Mathier, M. A., McGoon, M. D., Park, M. H., Rosenson, R. S., Rubin, L. J., Tapson, V. F., Varga, J. (2009). 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 53: 1573-1619 [Full Text]  
• Writing Committee Members, , McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., Mathier, M. A., McGoon, M. D., Park, M. H., Rosenson, R. S., Rubin, L. J., Tapson, V. F., Varga, J. (2009). 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. Circulation 119: 2250-2294 [Full Text]  
• Lewis, G. D. (2009). The role of the pulmonary vasculature in heart failure with preserved ejection fraction.. J Am Coll Cardiol 53: 1127-1129 [Full Text]  
• PAMIDI, S., MEHTA, S. (2009). Six-Minute Walk Test in Scleroderma-Associated Pulmonary Arterial Hypertension: Are We Counting What Counts?. The Journal of Rheumatology 36: 216-218 [Full Text]  
• Hofstee, H M A, Noordegraaf, A V., Voskuyl, A E, Dijkmans, B A C, Postmus, P E, Smulders, Y M, Serne, E H (2009). Nailfold capillary density is associated with the presence and severity of pulmonary arterial hypertension in systemic sclerosis. Ann Rheum Dis 68: 191-195 [Abstract] [Full Text]  
• McLaughlin, V., Strange, C. (2009). Opportunities and Challenges in the Study of Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 179: 91-92 [Full Text]  
• Condliffe, R., Kiely, D. G., Peacock, A. J., Corris, P. A., Gibbs, J. S. R., Vrapi, F., Das, C., Elliot, C. A., Johnson, M., DeSoyza, J., Torpy, C., Goldsmith, K., Hodgkins, D., Hughes, R. J., Pepke-Zaba, J., Coghlan, J. G. (2009). Connective Tissue Disease-associated Pulmonary Arterial Hypertension in the Modern Treatment Era. Am. J. Respir. Crit. Care Med. 179: 151-157 [Abstract] [Full Text]  
• Galiè, N., Manes, A. (2009). CHAPTER 24 Pulmonary Hypertension. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full Text]  
• (2008). Pulmonary arterial hypertension: models and mechanisms. Thorax 63: A27-A30 [Full Text]  
• Avouac, J, Juin, F, Wipff, J, Couraud, P O, Chiocchia, G, Kahan, A, Boileau, C, Uzan, G, Allanore, Y (2008). Circulating endothelial progenitor cells in systemic sclerosis: association with disease severity. Ann Rheum Dis 67: 1455-1460 [Abstract] [Full Text]  
• Sanchez-Roman, J., Opitz, C. F., Kowal-Bielecka, O., Garcia-Hernandez, F. J., Castillo-Palma, M. J., Pittrow, D., for the EPOSS-OMERACT Group, (2008). Screening for PAH in patients with systemic sclerosis: focus on Doppler echocardiography. Rheumatology (Oxford) 47: v33-v35 [Abstract] [Full Text]  
• Wells, A U, Hirani, N, on behalf of the BTS Interstitial Lung Disease Gui, (2008). Interstitial lung disease guideline. Thorax 63: v1-v58 [Full Text]  
• Denton, C P, Pope, J E, Peter, H-H, Gabrielli, A, Boonstra, A, van den Hoogen, F H J, Riemekasten, G, De Vita, S, Morganti, A, Dolberg, M, Berkani, O, Guillevin, L, (on behalf of the TRacleer Use in PAH associated w, (2008). Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis 67: 1222-1228 [Abstract] [Full Text]  
• Wipff, J., Avouac, J., Borderie, D., Zerkak, D., Lemarechal, H., Kahan, A., Boileau, C., Allanore, Y. (2008). Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin. Rheumatology (Oxford) 47: 972-975 [Abstract] [Full Text]  
• Overbeek, M. J., Lankhaar, J-W., Westerhof, N., Voskuyl, A. E., Boonstra, A., Bronzwaer, J. G. F., Marques, K. M. J., Smit, E. F., Dijkmans, B. A. C., Vonk-Noordegraaf, A. (2008). Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension. Eur Respir J 31: 1160-1166 [Abstract] [Full Text]  
• Avouac, J, Wipff, J, Kahan, A, Allanore, Y (2008). Effects of oral treatments on exercise capacity in systemic sclerosis related pulmonary arterial hypertension: a meta-analysis of randomised controlled trials. Ann Rheum Dis 67: 808-814 [Abstract] [Full Text]  
• Terrier, B., Tamby, M. C., Camoin, L., Guilpain, P., Broussard, C., Bussone, G., Yaici, A., Hotellier, F., Simonneau, G., Guillevin, L., Humbert, M., Mouthon, L. (2008). Identification of Target Antigens of Antifibroblast Antibodies in Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 177: 1128-1134 [Abstract] [Full Text]  
• Wilson, J W, du Bois, R M, King, T E Jr (2008). Challenges in pulmonary fibrosis: 8 {middle dot} The need for an international registry for idiopathic pulmonary fibrosis. Thorax 63: 285-287 [Abstract] [Full Text]  
• National Pulmonary Hypertension Centres of the UK, (2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Heart 94: i1-i41 [Full Text]  
• National Pulmonary Hypertension Centres of the UK, (2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax 63: ii1-ii41 [Full Text]  
• de Groote, P, Gressin, V, Hachulla, E, Carpentier, P, Guillevin, L, Kahan, A, Cabane, J, Frances, C, Lamblin, N, Diot, E, Patat, F, Sibilia, J, Petit, H, Cracowski, J-L, Clerson, P, Humbert, M, for the ItinerAIR-Scleroderma Investigators, (2008). Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann Rheum Dis 67: 31-36 [Abstract] [Full Text]  
• Coghlan, J.G., Davar, J. (2007). How should we assess right ventricular function in 2008?. Eur Heart J Suppl 9: H22-H28 [Abstract] [Full Text]  
• Girgis, R. E, Frost, A. E, Hill, N. S, Horn, E. M, Langleben, D., McLaughlin, V. V, Oudiz, R. J, Robbins, I. M, Seibold, J. R, Shapiro, S., Tapson, V. F, Barst, R. J (2007). Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis 66: 1467-1472 [Abstract] [Full Text]  
• Wipff, J., Kahan, A., Hachulla, E., Sibilia, J., Cabane, J., Meyer, O., Mouthon, L., Guillevin, L., Junien, C., Boileau, C., Allanore, Y. (2007). Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension. Rheumatology (Oxford) 46: 622-625 [Abstract] [Full Text]  
• Buch, M H, Denton, C P, Furst, D E, Guillevin, L, Rubin, L J, Wells, A U, Matucci-Cerinic, M, Riemekasten, G, Emery, P, Chadha-Boreham, H, Charef, P, Roux, S, Black, C M, Seibold, J R (2007). Submaximal exercise testing in the assessment of interstitial lung disease secondary to systemic sclerosis: reproducibility and correlations of the 6-min walk test. Ann Rheum Dis 66: 169-173 [Abstract] [Full Text]  
• Villalba, W. O., Sampaio-Barros, P. D., Pereira, M. C., Cerqueira, E. M. F. P., Leme, C. A. Jr, Marques-Neto, J. F., Paschoal, I. A. (2007). Six-Minute Walk Test for the Evaluation of Pulmonary Disease Severity in Scleroderma Patients. Chest 131: 217-222 [Abstract] [Full Text]  
• Coghlan, J. G., Handler, C. E. (2007). N-terminal brain natriuretic peptide in scleroderma-associated pulmonary arterial hypertension: reply. Eur Heart J 28: 141-141 [Full Text]  
• Collins, N., Bastian, B., Quiqueree, L., Jones, C., Morgan, R., Reeves, G. (2006). Abnormal pulmonary vascular responses in patients registered with a systemic autoimmunity database: Pulmonary Hypertension Assessment and Screening Evaluation using stress echocardiography (PHASE-I). Eur J Echocardiogr 7: 439-446 [Abstract] [Full Text]  
• Denton, C P, Humbert, M, Rubin, L, Black, C M (2006). Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Ann Rheum Dis 65: 1336-1340 [Abstract] [Full Text]  
• Distler, O., Pignone, A. (2006). Pulmonary arterial hypertension and rheumatic diseases--from diagnosis to treatment. Rheumatology (Oxford) 45: iv22-iv25 [Abstract] [Full Text]  
• Kahler, C. M., Colleselli, D. (2006). Pulmonary arterial hypertension (PAH) in connective tissue diseases. Rheumatology (Oxford) 45: iii11-iii13 [Abstract] [Full Text]  
• Callejas-Rubio, J. L., Moreno-Escobar, E., Martin-de la Fuente, P., Ortego-Centeno, N. (2006). Pulmonary hypertension and exercise echocardiography. Eur J Echocardiogr 7: 261-262 [Full Text]  
• Williams, M H, Das, C, Handler, C E, Akram, M R, Davar, J, Denton, C P, Smith, C J, Black, C M, Coghlan, J G (2006). Systemic sclerosis associated pulmonary hypertension: improved survival in the current era. Heart 92: 926-932 [Abstract] [Full Text]  
• Williams, M. H., Handler, C. E., Akram, R., Smith, C. J., Das, C., Smee, J., Nair, D., Denton, C. P., Black, C. M., Coghlan, J. G. (2006). Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur Heart J 27: 1485-1494 [Abstract] [Full Text]  
• Coghlan, J G, Handler, C (2006). Connective tissue associated pulmonary arterial hypertension. Lupus 15: 138-142 [Abstract]  
• Mouthon, L., Guillevin, L., Humbert, M. (2005). Pulmonary arterial hypertension: an autoimmune disease?. Eur Respir J 26: 986-988 [Full Text]  
• Nicolls, M. R., Taraseviciene-Stewart, L., Rai, P. R., Badesch, D. B., Voelkel, N. F. (2005). Autoimmunity and pulmonary hypertension: a perspective. Eur Respir J 26: 1110-1118 [Abstract] [Full Text]  
• Ferri, C, Giuggioli, D, Sebastiani, M, Colaci, M, Emdin, M (2005). Heart involvement and systemic sclerosis. Lupus 14: 702-707 [Abstract]  
• Galie, N, Manes, A, Farahani, K V, Pelino, F, Palazzini, M, Negro, L, Romanazzi, S, Branzi, A (2005). Pulmonary arterial hypertension associated to connective tissue diseases. Lupus 14: 713-717 [Abstract]  
• Tamby, M C, Chanseaud, Y, Humbert, M, Fermanian, J, Guilpain, P, Garcia-de-la-Pena-Lefebvre, P, Brunet, S, Servettaz, A, Weill, B., Simonneau, G, Guillevin, L, Boissier, M C, Mouthon, L (2005). Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax 60: 765-772 [Abstract] [Full Text]  
• Hesselstrand, R., Ekman, R., Eskilsson, J., Isaksson, A., Scheja, A., Ohlin, A.-K., Akesson, A. (2005). Screening for pulmonary hypertension in systemic sclerosis: the longitudinal development of tricuspid gradient in 227 consecutive patients, 1992-2001. Rheumatology (Oxford) 44: 366-371 [Abstract] [Full Text]  
• Black, C. (2005). Pulmonary arterial hypertension: are we doing enough to identify systemic sclerosis patients at high risk of this rare condition?. Rheumatology (Oxford) 44: 141-142 [Full Text]  
• Task Force members, , Galie, N., Torbicki, A., Barst, R., Dartevelle, P., Haworth, S., Higenbottam, T., Olschewski, H., Peacock, A., Pietra, G., Rubin, L. J., Simonneau, G. (2004). Guidelines on diagnosis and treatment of pulmonary arterial hypertension: The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 25: 2243-2278 [Full Text]  
• Hachulla, E, Coghlan, J G (2004). A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann Rheum Dis 63: 1009-1014 [Abstract] [Full Text]