{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:40:18Z","timestamp":1790804418134,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The early diagnosis of pulmonary arterial hypertension (PAH) is a major determinant of prognosis in patients affected by connective tissue diseases (CTDs) complicated by PAH. In the present paper we investigated the diagnostic accuracy of cardiopulmonary exercise testing (CPET) in this specific setting. We recorded clinical and laboratory data of 131 patients who underwent a CPET at a pulmonary hypertension clinic. Out of them, 112 (85.5%) had a diagnosis of CTDs; 8 (6.1%) received a diagnosis of CTDs-PAH and 11 (8.4%) were affected PH of different etiology. Among CPET parameters the following parameters showed the best diagnostic performance for PAH: peak volume of oxygen uptake (VO2; AUC: 0.845, CI95% 0.767\u20130.904), ratio between ventilation and volume of exhaled carbon dioxide (VE\/VCO2 slope; AUC: 0.888, CI95%: 0.817\u20130.938) and end-tidal partial pressures (PetCO2; AUC: 0.792, CI95%: 0.709\u20130.861). These parameters were comparable among CTDs-PAH and PH of different etiology. The diagnostic performance was even improved by creating a composite score which included all the three parameters identified. In conclusion, CPET is a very promising tool for the stratification of risk of PAH among CTDs patients; the use of composite measures may improve diagnostic performance.<\/jats:p>","DOI":"10.3390\/ph14040342","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T21:27:44Z","timestamp":1617917264000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cardiopulmonary Exercise Testing Is an Accurate Tool for the Diagnosis of Pulmonary Arterial Hypertension in Scleroderma Related Diseases"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-8736","authenticated-orcid":false,"given":"Mattia","family":"Bellan","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"},{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"},{"name":"CAAD, (Center for Translational Research on Autoimmune and Allergic Disease) Maggiore della Carit\u00e0 Hospital and Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailia","family":"Giubertoni","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"},{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Piccinino","sequence":"additional","affiliation":[{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Buffa","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Cromi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Sola","sequence":"additional","affiliation":[{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pedrazzoli","sequence":"additional","affiliation":[{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Calzaducca","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Zecca","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-8734","authenticated-orcid":false,"given":"Filippo","family":"Patrucco","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"},{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Patti","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"},{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-9158","authenticated-orcid":false,"given":"Pier Paolo","family":"Sainaghi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"},{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"},{"name":"CAAD, (Center for Translational Research on Autoimmune and Allergic Disease) Maggiore della Carit\u00e0 Hospital and Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Pirisi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"},{"name":"\u201cAOU Maggiore della Carit\u00e0\u201d Hospital, 28100 Novara, Italy"},{"name":"CAAD, (Center for Translational Research on Autoimmune and Allergic Disease) Maggiore della Carit\u00e0 Hospital and Universit\u00e0 del Piemonte Orientale UPO, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","article-title":"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)","volume":"37","author":"Humbert","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11926-017-0697-x","article-title":"cardiopulmonary manifestations of collagen vascular diseases","volume":"19","author":"Jawad","year":"2017","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1183\/09031936.00057010","article-title":"French pulmonary arterial hypertension network. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension","volume":"36","author":"Humbert","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_4","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":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13075-015-0517-5","article-title":"A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis","volume":"17","author":"Hao","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2696173","DOI":"10.1155\/2020\/2696173","article-title":"Role of Gas6 and TAM receptors in the identification of cardiopulmonary involvement in systemic sclerosis and scleroderma spectrum disorders","volume":"2020","author":"Bellan","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4981982","DOI":"10.1155\/2019\/4981982","article-title":"Red cell distribution width and platelet count as biomarkers of pulmonary arterial hypertension in patients with connective tissue disorders","volume":"2019","author":"Bellan","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1136\/heartjnl-2016-309981","article-title":"Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis","volume":"103","author":"Dumitrescu","year":"2017","journal-title":"Heart"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/rheumatology\/kez473","article-title":"Cardiopulmonary exercise testing in a combined screening approach to individuate pulmonary arterial hypertension in systemic sclerosis","volume":"59","author":"Santaniello","year":"2020","journal-title":"Rheumatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/rheumatology\/ker269","article-title":"Trends in mortality in patients with systemic sclerosis over 40 years: A systematic review and meta-analysis of cohort studies","volume":"51","author":"Elhai","year":"2012","journal-title":"Rheumatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1136\/ard.2009.114264","article-title":"Causes and risk factors for death in systemic sclerosis: A study from the EULAR scleroderma trials and research (EUSTAR) database","volume":"69","author":"Tyndall","year":"2010","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1164\/rccm.200806-953OC","article-title":"Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era","volume":"179","author":"Condliffe","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1136\/ard.62.11.1088","article-title":"Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: Application of a registry approach","volume":"62","author":"Mukerjee","year":"2003","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1800678","DOI":"10.1183\/13993003.00678-2018","article-title":"Haemodynamics and serial risk assessment in systemic sclerosis associated pulmonary arterial hypertension","volume":"52","author":"Weatherald","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1378\/chest.13-3014","article-title":"Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry","volume":"146","author":"Chung","year":"2014","journal-title":"Chest"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/annrheumdis-2019-216476","article-title":"Haemodynamic phenotypes and survival in patients with systemic sclerosis: The impact of the new definition of pulmonary arterial hypertension","volume":"79","author":"Xanthouli","year":"2020","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1136\/annrheumdis-2016-209909","article-title":"EUSTAR coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis","volume":"76","author":"Fransen","year":"2017","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/CRD.0000000000000270","article-title":"Right heart catheterization-related complications: A review of the literature and best practices","volume":"28","author":"Chen","year":"2020","journal-title":"Cardiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"190023","DOI":"10.1183\/16000617.0023-2019","article-title":"Screening for pulmonary arterial hypertension in systemic sclerosis","volume":"28","author":"Weatherald","year":"2019","journal-title":"Eur. Respir. Rev."},{"key":"ref_20","first-page":"S103","article-title":"Exercise tolerance in systemic sclerosis patients without pulmonary impairment: Correlation with clinical variables","volume":"32","author":"Rosato","year":"2014","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","article-title":"2013 classification criteria for systemic sclerosis: An American college of rheumatolo-gy\/European league against rheumatism collaborative initiative","volume":"72","author":"Hoogen","year":"2013","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_22","unstructured":"Sharp, G. (1987). Preliminary diagnostic criteria for classification of mixed connective tissue disease. Mixed Connective Tissue Disease and Antinuclear Antibodies, Elsevier."},{"key":"ref_23","first-page":"14","article-title":"Scleroderma overlap syndrome","volume":"13","year":"2011","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_24","first-page":"S14","article-title":"Undifferentiated connective tissue diseases in 2004","volume":"22","author":"Mosca","year":"2004","journal-title":"Clin. Exp. Rheumatol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/4\/342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:12:07Z","timestamp":1760364727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/4\/342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,8]]},"references-count":24,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ph14040342"],"URL":"https:\/\/doi.org\/10.3390\/ph14040342","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,8]]}}}