Survival and factors influencing survival in systemic sclerosis patients with pulmonary arterial hypertension
Abstract
OBJECTIVE
To assess the survival rates of individuals diagnosed with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), while also identifying factors that may be associated with increased mortality.
METHODS
We conducted a retrospective unmatched case-control study using data from systemic sclerosis (SSc) patients with associated pulmonary arterial hypertension (PAH) at Chiangrai Prachanukroh Hospital, Thailand, covering the period from January 2012 to March 2023. We gathered information on patient characteristics, clinical presentation, laboratory results, and administered treatments. The primary endpoint of our investigation was the survival status of the patients.
RESULTS
There were 112 patients with Sac and PAH included in the analysis with the median survival time was 48 months withe the 5-year survival rate was 48.21% (95% confidence interval [CI], 38.71 to 57.08). Among these, 58 patients (51.7%) died. In our multivariable Cox regression analysis, we identified several factors associated with differing mortality rates. Specifically, New York Heart Association Classification (NYHC) III-IV was strongly associated with a higher mortality rate (adjusted hazard ratio [AHR] 10.02; 95% confidence interval [CI], 4.88 to 20.57; P<0.001), as was hemoglobin levels below 10 g/dL (AHR, 7.67; 95% CI, 3.97 to 14.82; P<0.001), and the presence of moderate pericardial effusion (AHR, 10.29; 95% CI, 1.65 to 64.08; P=0.012). In contrast, patients with stage 3 chronic kidney disease exhibited a lower mortality rate (AHR, 0.15; 95% CI, 0.03 to 0.78; P=0.023).
CONCLUSION
In our study, we observed a relatively high 5-year survival rate, which contrasts with findings from other studies. Our analysis revealed that individuals classified as NYHC III-IV, those with hemoglobin levels below 10 g/dL, and those with moderate pericardial effusion experienced a significantly higher mortality rate. Conversely, patients in CKD stage 3 demonstrated a lower mortality rate in our study.
References
REFERNCE.
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3. MacGregor A, Canavan R, Knight C, et al. Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology 2001;40:453-9.
4. Williams MH, Das C, Handler CE, et al. Systemic sclerosis associated pulmonary hypertension: improved survival in the current era. Heart 2006;92:926-32.
5. Solomon JJ, Olson AL, Fischer A, Bull T, Brown KK, Raghu G. Scleroderma lung disease. European respiratory review 2013;22:6-19.
6. Scalapino K, Arkachaisri T, Lucas M, et al. Childhood onset systemic sclerosis: classification, clinical and serologic features, and survival in comparison with adult onset disease. The Journal of rheumatology 2006;33:1004-13.
7. Mathai SC, Hummers LK, Champion HC, et al. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 2009;60:569-77.
8. Altman RD, Medsger Jr TA, Bloch DA, Michel BA. Predictors of survival in systemic sclerosis (scleroderma). Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 1991;34:403-13.
9. Launay D, Humbert M, Berezne A, et al. Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. Chest 2011;140:1016-24.
10. Mukerjee D, St George D, Coleiro B, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Annals of the rheumatic diseases 2003;62:1088-93.
11. Van Den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis & Rheumatism 2013;65:2737-47.
12. Montani D, Günther S, Dorfmüller P, et al. Pulmonary arterial hypertension. Orphanet J Rare Dis 2013;8:97.
13. Le Pavec J, Humbert M, Mouthon L, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. American journal of respiratory and critical care medicine 2010;181:1285-93.
14. Reddy YN, Olson TP, Obokata M, Melenovsky V, Borlaug BA. Hemodynamic correlates and diagnostic role of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. JACC: Heart Failure 2018;6:665-75.
15. Steckelberg RC, Tseng AS, Nishimura R, Ommen S, Sorajja P. Derivation of mean pulmonary artery pressure from noninvasive parameters. Journal of the American Society of Echocardiography 2013;26:464-8.
16. Koestenberger M, Apitz C, Abdul-Khaliq H, Hansmann G. Transthoracic echocardiography for the evaluation of children and adolescents with suspected or confirmed pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 2016;102:ii14-ii22.
17. Chemla D, Castelain V, Herve P, Lecarpentier Y, Brimioulle S. Haemodynamic evaluation of pulmonary hypertension. European Respiratory Journal 2002;20:1314-31.
18. Volkmann ER, Tashkin DP, Sim M, et al. Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts. Annals of the rheumatic diseases 2019;78:122-30.
19. Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003;123:344-50.
20. Chaisson NF, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. Chest 2013;144:1346-56.
21. D'Alto M, Romeo E, Argiento P, et al. Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension. International journal of cardiology 2013;168:4058-62.
22. Armstrong HF, Schulze PC, Bacchetta M, Thirapatarapong W, Bartels MN. Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation. Respirology 2014;19:675-82.
23. Soofi MA, Shah MA, AlQadhi AM, AlAnazi AM, Alshehri WM, Umair A. Sensitivity and Specificity of Pulmonary Artery Pressure Measurement in Echocardiography and Correlation with Right Heart Catheterization. J Saudi Heart Assoc 2021;33:228-36.
24. Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis. Heart 2011;97:612-22.
25. Griffiths B, Miles S, Moss H, Robertson R, Veale D, Emery P. Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function. The Journal of Rheumatology 2002;29:2371-8.
26. Wells AU. Pulmonary function tests in connective tissue disease. Seminars in respiratory and critical care medicine; 2007: Copyright© 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New …. p. 379-88.
27. Adler S, Huscher D, Siegert E, et al. Systemic sclerosis associated interstitial lung disease-individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group. Arthritis research & therapy 2018;20:1-12.
28. Hidekata Yasuoka M, Masataka Kuwana M. Combined Interstitial Lung Disease and Pulmonary Hypertension in Systemic Sclerosis: Pathophysiology and Management. Current Medical Literature 2012;3:105.
29. Sangani RA, Lui JK, Gillmeyer KR, et al. Clinical characteristics and outcomes in pulmonary manifestations of systemic sclerosis: Contribution from pulmonary hypertension and interstitial lung disease severity. Pulmonary Circulation 2022;12:e12117.
30. Horimoto AMC, Costa IPd. Overlap between systemic sclerosis and rheumatoid arthritis: a distinct clinical entity? Revista brasileira de reumatologia 2016;56:287-98.
31. Bakker ME, Ninaber MK, Stolk J, et al. Lung density and pulmonary artery diameter are predictors of pulmonary hypertension in systemic sclerosis. Journal of thoracic imaging 2017;32:391-7.
32. Le Pavec J, Launay D, Mathai SC, Hassoun PM, Humbert M. Scleroderma lung disease. Clinical reviews in allergy & immunology 2011;40:104-16.
33. Glynn P, Hale S, Hussain T, Freed BH. Cardiovascular Imaging for Systemic Sclerosis Monitoring and Management. Front Cardiovasc Med 2022;9:846213.
34. Chung L, Farber HW, Benza R, et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest 2014;146:1494-504.
35. Lee P, Langevitz P, Alderdice C, et al. Mortality in systemic sclerosis (scleroderma). QJM: An International Journal of Medicine 1992;82:139-48.
36. Kolstad KD, Li S, Steen V, et al. Long-term outcomes in systemic sclerosis-associated pulmonary arterial hypertension from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS). Chest 2018;154:862-71.
37. Yaghi S, Novikov A, Trandafirescu T. Clinical update on pulmonary hypertension. Journal of Investigative Medicine 2020;68:821-7.
38. Steen V, Medsger Jr TA. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis & Rheumatism 2003;48:516-22.
39. McLaughlin VV, Langer A, Tan M, et al. Contemporary trends in the diagnosis and management of pulmonary arterial hypertension: an initiative to close the care gap. Chest 2013;143:324-32.
40. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004;126:14S-34S.
41. Avouac J, Airò P, Meune C, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. The Journal of rheumatology 2010;37:2290-8.
1. Ferri C, Valentini G, Cozzi F, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine 2002;81:139-53.
2. Lefevre G, Dauchet L, Hachulla E, et al. Survival and prognostic factors in systemic sclerosis–associated pulmonary hypertension: a systematic review and meta‐analysis. Arthritis & Rheumatism 2013;65:2412-23.
3. MacGregor A, Canavan R, Knight C, et al. Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology 2001;40:453-9.
4. Williams MH, Das C, Handler CE, et al. Systemic sclerosis associated pulmonary hypertension: improved survival in the current era. Heart 2006;92:926-32.
5. Solomon JJ, Olson AL, Fischer A, Bull T, Brown KK, Raghu G. Scleroderma lung disease. European respiratory review 2013;22:6-19.
6. Scalapino K, Arkachaisri T, Lucas M, et al. Childhood onset systemic sclerosis: classification, clinical and serologic features, and survival in comparison with adult onset disease. The Journal of rheumatology 2006;33:1004-13.
7. Mathai SC, Hummers LK, Champion HC, et al. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 2009;60:569-77.
8. Altman RD, Medsger Jr TA, Bloch DA, Michel BA. Predictors of survival in systemic sclerosis (scleroderma). Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 1991;34:403-13.
9. Launay D, Humbert M, Berezne A, et al. Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. Chest 2011;140:1016-24.
10. Mukerjee D, St George D, Coleiro B, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Annals of the rheumatic diseases 2003;62:1088-93.
11. Van Den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis & Rheumatism 2013;65:2737-47.
12. Montani D, Günther S, Dorfmüller P, et al. Pulmonary arterial hypertension. Orphanet J Rare Dis 2013;8:97.
13. Le Pavec J, Humbert M, Mouthon L, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. American journal of respiratory and critical care medicine 2010;181:1285-93.
14. Reddy YN, Olson TP, Obokata M, Melenovsky V, Borlaug BA. Hemodynamic correlates and diagnostic role of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. JACC: Heart Failure 2018;6:665-75.
15. Steckelberg RC, Tseng AS, Nishimura R, Ommen S, Sorajja P. Derivation of mean pulmonary artery pressure from noninvasive parameters. Journal of the American Society of Echocardiography 2013;26:464-8.
16. Koestenberger M, Apitz C, Abdul-Khaliq H, Hansmann G. Transthoracic echocardiography for the evaluation of children and adolescents with suspected or confirmed pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 2016;102:ii14-ii22.
17. Chemla D, Castelain V, Herve P, Lecarpentier Y, Brimioulle S. Haemodynamic evaluation of pulmonary hypertension. European Respiratory Journal 2002;20:1314-31.
18. Volkmann ER, Tashkin DP, Sim M, et al. Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts. Annals of the rheumatic diseases 2019;78:122-30.
19. Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003;123:344-50.
20. Chaisson NF, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. Chest 2013;144:1346-56.
21. D'Alto M, Romeo E, Argiento P, et al. Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension. International journal of cardiology 2013;168:4058-62.
22. Armstrong HF, Schulze PC, Bacchetta M, Thirapatarapong W, Bartels MN. Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation. Respirology 2014;19:675-82.
23. Soofi MA, Shah MA, AlQadhi AM, AlAnazi AM, Alshehri WM, Umair A. Sensitivity and Specificity of Pulmonary Artery Pressure Measurement in Echocardiography and Correlation with Right Heart Catheterization. J Saudi Heart Assoc 2021;33:228-36.
24. Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis. Heart 2011;97:612-22.
25. Griffiths B, Miles S, Moss H, Robertson R, Veale D, Emery P. Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function. The Journal of Rheumatology 2002;29:2371-8.
26. Wells AU. Pulmonary function tests in connective tissue disease. Seminars in respiratory and critical care medicine; 2007: Copyright© 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New …. p. 379-88.
27. Adler S, Huscher D, Siegert E, et al. Systemic sclerosis associated interstitial lung disease-individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group. Arthritis research & therapy 2018;20:1-12.
28. Hidekata Yasuoka M, Masataka Kuwana M. Combined Interstitial Lung Disease and Pulmonary Hypertension in Systemic Sclerosis: Pathophysiology and Management. Current Medical Literature 2012;3:105.
29. Sangani RA, Lui JK, Gillmeyer KR, et al. Clinical characteristics and outcomes in pulmonary manifestations of systemic sclerosis: Contribution from pulmonary hypertension and interstitial lung disease severity. Pulmonary Circulation 2022;12:e12117.
30. Horimoto AMC, Costa IPd. Overlap between systemic sclerosis and rheumatoid arthritis: a distinct clinical entity? Revista brasileira de reumatologia 2016;56:287-98.
31. Bakker ME, Ninaber MK, Stolk J, et al. Lung density and pulmonary artery diameter are predictors of pulmonary hypertension in systemic sclerosis. Journal of thoracic imaging 2017;32:391-7.
32. Le Pavec J, Launay D, Mathai SC, Hassoun PM, Humbert M. Scleroderma lung disease. Clinical reviews in allergy & immunology 2011;40:104-16.
33. Glynn P, Hale S, Hussain T, Freed BH. Cardiovascular Imaging for Systemic Sclerosis Monitoring and Management. Front Cardiovasc Med 2022;9:846213.
34. Chung L, Farber HW, Benza R, et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest 2014;146:1494-504.
35. Lee P, Langevitz P, Alderdice C, et al. Mortality in systemic sclerosis (scleroderma). QJM: An International Journal of Medicine 1992;82:139-48.
36. Kolstad KD, Li S, Steen V, et al. Long-term outcomes in systemic sclerosis-associated pulmonary arterial hypertension from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS). Chest 2018;154:862-71.
37. Yaghi S, Novikov A, Trandafirescu T. Clinical update on pulmonary hypertension. Journal of Investigative Medicine 2020;68:821-7.
38. Steen V, Medsger Jr TA. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis & Rheumatism 2003;48:516-22.
39. McLaughlin VV, Langer A, Tan M, et al. Contemporary trends in the diagnosis and management of pulmonary arterial hypertension: an initiative to close the care gap. Chest 2013;143:324-32.
40. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004;126:14S-34S.
41. Avouac J, Airò P, Meune C, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. The Journal of rheumatology 2010;37:2290-8.
Published
2023-09-27
How to Cite
sirijanchune, piyaporn, Lhakum, P., & Chueamuangphan, N. (2023). Survival and factors influencing survival in systemic sclerosis patients with pulmonary arterial hypertension. The Clinical Academia, 47(3), 79-88. Retrieved from https://journal.axiomlaboratory.com/index.php/theclinicalacademia/article/view/50
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Articles
