Hemodynamic Reclassification Under the 2022 Definition in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Single-Center Cohort Study

Öz

Introduction/Objectives: The 2022 pulmonary hypertension guidelines lowered the hemodynamic thresholds for pulmonary hypertension and pulmonary arterial hypertension, potentially expanding the spectrum of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). The profile of patients identified only by the updated definition remains incompletely characterized. To evaluate the reclassification impact of the 2022 hemodynamic definition in a catheterization-based cohort of clinically adjudicated CTD-associated Group 1 PAH. Methods: We retrospectively analyzed 27 patients with CTD-associated Group 1 PAH. Patients fulfilling previous mPAP and PVR thresholds were classified as established PAH, whereas those fulfilling the 2022 classification but not the previous definition were classified as 2022-only early CTD-PAH. Clinical, pulmonary function, echocardiographic, and hemodynamic variables were compared. Exploratory high burden was defined as ≥4 positive components among PVR ≥5 WU, mPAP ≥35 mmHg, right atrial mean pressure ≥8 mmHg, cardiac index <2.5 L/min/m², NT-proBNP/ProBNP ≥300, and TAPSE <18 mm. Results: Overall, 22 patients (81.5%) met the previous definition, while 5 (18.5%) were classified as 2022-only early CTD-PAH. Compared with established PAH, the 2022-only group had lower mPAP, sPAP, dPAP, PVR, and TPG, with more preserved FVC. ILD was absent in this group. No 2022-only patient had a high-burden phenotype, compared with 45.5% of established PAH patients. Conclusion: In this CTD-associated Group 1 PAH cohort, the 2022 definition reclassified nearly one-fifth of patients as 2022-only early CTD-PAH. These patients demonstrated a milder hemodynamic profile, preserved pulmonary function, absence of ILD, and no high-burden phenotype, supporting the clinical relevance of early hemodynamic recognition in CTD-PAH. Keywords: Hypertension, Pulmonary; Connective Tissue Diseases; Hemodynamics.

Anahtar Kelimeler

• Hypertension, Pulmonary
• Connective Tissue Diseases
• Hemodynamics

Bağ Dokusu Hastalıklarına Bağlı Pulmoner Arteriyel Hipertansiyonda 2022 Tanımı Kapsamında Hemodinamik Yeniden Sınıflandırma: Tek Merkezli Kohort Çalışması

Öz

Giriş/Amaç: 2022 pulmoner hipertansiyon kılavuzları, pulmoner hipertansiyon ve pulmoner arteriyel hipertansiyon için hemodinamik eşikleri düşürerek bağ dokusu hastalığı ilişkili pulmoner arteriyel hipertansiyonun (CTD-PAH) tanısal kapsamını genişletmiştir. Ancak yalnızca güncel tanımla saptanan hastaların klinik ve hemodinamik profili yeterince tanımlanmamıştır. Bu çalışmada, sağ kalp kateterizasyonu ile değerlendirilmiş ve klinik olarak CTD-associated Group 1 PAH kabul edilmiş bir kohortta 2022 hemodinamik tanımının yeniden sınıflandırma etkisinin değerlendirilmesi amaçlandı. Yöntem: Retrospektif olarak 27 CTD-associated Group 1 PAH hastası analiz edildi. Önceki mPAP ve PVR eşiklerini karşılayan hastalar established PAH; 2022 sınıflamasını karşılayıp önceki tanımı karşılamayan hastalar ise 2022-only early CTD-PAH olarak sınıflandırıldı. Klinik, solunum fonksiyon, ekokardiyografik ve hemodinamik değişkenler karşılaştırıldı. Keşifsel high-burden fenotip, PVR ≥5 WU, mPAP ≥35 mmHg, sağ atriyum ortalama basıncı ≥8 mmHg, kardiyak indeks <2.5 L/dk/m², NT-proBNP/ProBNP ≥300 ve TAPSE <18 mm bileşenlerinden en az dördünün varlığı olarak tanımlandı. Bulgular: Toplam 22 hasta (%81.5) önceki tanımı karşılarken, 5 hasta (%18.5) 2022-only early CTD-PAH olarak sınıflandırıldı. Established PAH ile karşılaştırıldığında, 2022-only grupta mPAP, sPAP, dPAP, PVR ve TPG daha düşük, FVC daha korunmuştu. Bu grupta ILD ve high-burden fenotip saptanmadı; established PAH grubunda high-burden oranı %45.5 idi. Sonuç: 2022 tanımı, CTD-associated Group 1 PAH kohortunun yaklaşık beşte birini 2022-only early CTD-PAH olarak yeniden sınıflandırdı. Bu hastalar daha hafif hemodinamik profil, korunmuş solunum fonksiyonu, ILD yokluğu ve high-burden fenotipin bulunmamasıyla ayrıştı. Anahtar Kelimeler: Pulmoner Hipertansiyon, Bağ Doku Hastalıkları, Hemodinami

Anahtar Kelimeler

• Pulmoner Hipertansiyon
• Bağ Doku Hastalıkları
• Hemodinami

Kaynakça

1. Chung L, Liu J, Parsons L, Hassoun PM, McGoon M, Badesch DB, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138(6):1383–1394. doi: 10.1378/chest.10-0260.
2. Weatherald J, Montani D, Jevnikar M, Jaïs X, Savale L, Humbert M. Screening for pulmonary arterial hypertension in systemic sclerosis. Eur Respir Rev. 2019;28(153):190023. doi: 10.1183/16000617.0023-2019.
3. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618–3731. doi: 10.1093/eurheartj/ehac237.
4. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, Williams PG, Souza R. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. doi: 10.1183/13993003.01913-2018.
5. 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(4):1074–1084. doi: 10.1002/art.37838.
6. Puigrenier S, Giovannelli J, Lamblin N, De Groote P, Fertin M, Bervar JF, et al. Mild pulmonary hemodynamic alterations in patients with systemic sclerosis: relevance of the new 2022 ESC/ERS definition of pulmonary hypertension and impact on mortality. Respir Res. 2022;23(1):284. doi: 10.1186/s12931-022-02205-4.
7. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737–2747. doi: 10.1002/art.38098.
8. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581. doi: 10.1002/art.27584.

9. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome. Arthritis Rheumatol. 2017;69(1):35–45. doi: 10.1002/art.39859.
10. Hoeper MM, Pausch C, Olsson KM, Huscher D, Pittrow D, Grünig E, et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. 2022;60(1):2102311. doi: 10.1183/13993003.02311-2021.
11. Benza RL, Gomberg-Maitland M, Elliott CG, Farber HW, Foreman AJ, Frost AE, et al. Predicting survival in patients with pulmonary arterial hypertension: the REVEAL Risk Score Calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies. Chest. 2019;156(2):323–337. doi: 10.1016/j.chest.2019.02.004.
12. Kovacs G, Olschewski H. The definition of pulmonary hypertension: history, practical implications and current controversies. Breathe. 2021;17(3):210076. doi: 10.1183/20734735.0076-2021.
13. Visovatti SH, Distler O, Coghlan JG, Denton CP, Grünig E, Bonderman D, et al. Borderline pulmonary arterial pressure in systemic sclerosis patients: a post-hoc analysis of the DETECT study. Arthritis Res Ther. 2014;16:493. doi: 10.1186/s13075-014-0493-1.
14. Bae S, Saggar R, Bolster MB, Chung L, Csuka ME, Derk C, et al. Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry. Ann Rheum Dis. 2012;71(8):1335–1342. doi: 10.1136/annrheumdis-2011-200546.
15. Nagel C, Marra AM, Benjamin N, Blank N, Cittadini A, Coghlan G, et al. Reduced right ventricular output reserve in patients with systemic sclerosis and mildly elevated pulmonary artery pressure. Arthritis Rheumatol. 2019;71(5):805–816. doi: 10.1002/art.40814.
16. Coghlan JG, Wolf M, Distler O, Denton CP, Doelberg M, Harutyunova S, et al. Incidence of pulmonary hypertension and determining factors in patients with systemic sclerosis. Eur Respir J. 2018;51(4):1701197. doi: 10.1183/13993003.01197-2017.
17. Pan Z, Marra AM, Benjamin N, Eichstaedt CA, Blank N, Bossone E, et al. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study). Arthritis Res Ther. 2019;21(1):217. doi: 10.1186/s13075-019-1981-0.
18. Karia N, Howard L, Johnson M, Kiely DG, Lordan J, McCabe C, et al. Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS Guidelines: the EVIDENCE-PAH UK study. Eur Heart J. 2023;44(44):4678–4692. doi: 10.1093/eurheartj/ehad532.
19. Maron BA, Brittain EL, Hess E, Waldo SW, Barón AE, Huang S, et al. Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study. Lancet Respir Med. 2020;8(9):873–884. doi: 10.1016/S2213-2600(20)30317-9.
20. Maron BA, Hess E, Maddox TM, Opotowsky AR, Tedford RJ, Lahm T, et al. Association of borderline pulmonary hypertension with mortality and hospitalization in a large patient cohort: insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation. 2016;133(13):1240–1248. doi: 10.1161/CIRCULATIONAHA.115.020207.
21. Kolte D, Lakshmanan S, Jankowich MD, Brittain EL, Maron BA, Choudhary G. Mild pulmonary hypertension is associated with increased mortality: a systematic review and meta-analysis. J Am Heart Assoc. 2018;7(18):e009729. doi: 10.1161/JAHA.118.009729.
22. Coghlan JG, Denton CP, Grünig E, Bonderman D, Distler O, Khanna D, et al.; DETECT Study Group. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–1349. doi: 10.1136/annrheumdis-2013-203301.
23. Humbert M, Yaici A, de Groote P, Montani D, Sitbon O, Launay D, 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. doi: 10.1002/art.30541.
24. Brown Z, Proudman S, Morrisroe K, Stevens W, Hansen D, Nikpour M. Screening for the early detection of pulmonary arterial hypertension in patients with systemic sclerosis: a systematic review and meta-analysis of long-term outcomes. Semin Arthritis Rheum. 2021;51(3):495–512. doi: 10.1016/j.semarthrit.2021.03.011.
25. Kolstad KD, Li S, Steen V, Chung L; PHAROS Investigators. Long-term outcomes in systemic sclerosis-associated pulmonary arterial hypertension from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry. Chest. 2018;154(4):862–871. doi: 10.1016/j.chest.2018.05.002.
26. Lefèvre G, Dauchet L, Hachulla E, Montani D, Sobanski V, Lambert M, et al. Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Arthritis Rheum. 2013;65(9):2412–2423. doi: 10.1002/art.38029.
27. Launay D, Sitbon O, Hachulla E, Mouthon L, Gressin V, Rottat L, et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. Ann Rheum Dis. 2013;72(12):1940–1946. doi: 10.1136/annrheumdis-2012-202489.
28. Mathai SC, Hummers LK, Champion HC, Wigley FM, Zaiman A, Hassoun PM, Girgis RE. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009;60(2):569–577. doi: 10.1002/art.24267.
29. Launay D, Humbert M, Berezne A, Cottin V, Allanore Y, Couderc LJ, et al. Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. Chest. 2011;140(4):1016–1024. doi: 10.1378/chest.10-2473.
30. Young A, Vummidi D, Visovatti S, Homer K, Wilhalme H, White ES, Flaherty K, McLaughlin V, Khanna D. Prevalence, treatment, and outcomes of coexistent pulmonary hypertension and interstitial lung disease in systemic sclerosis. Arthritis Rheumatol. 2019;71(8):1339–1349. doi: 10.1002/art.40862.
31. Kato M, Atsumi T. Pulmonary arterial hypertension associated with connective tissue diseases: a review focusing on distinctive clinical aspects. Eur J Clin Invest. 2018;48(2):e12876. doi: 10.1111/eci.12876.
32. Haque A, Kiely DG, Kovacs G, Thompson AAR, Condliffe R. Pulmonary hypertension phenotypes in patients with systemic sclerosis. Eur Respir Rev. 2021;30(161):210053. doi: 10.1183/16000617.0053-2021.
33. Benza RL, Kanwar MK, Raina A, Scott JV, Zhao CL, Selej M, et al. Development and validation of an abridged version of the REVEAL 2.0 Risk Score Calculator, REVEAL Lite 2, for use in patients with pulmonary arterial hypertension. Chest. 2021;159(1):337–346. doi: 10.1016/j.chest.2020.08.2069.