Background In this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc).
Methods In SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses.
Results The final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21–24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21–24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (p<0.001), TAPSE (p=0.004) and pulmonary arterial compliance (p<0.001). A PVR ≥2 WU was associated with reduced long-term survival (p=0.002). PVR and 6MWD were independent prognostic predictors in multivariate analysis.
Conclusion The data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.
- systemic sclerosis
- outcomes research
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NB and OD are joint senior authors.
PX and SJ are joint first authors.
Handling editor Josef S Smolen
Contributors PX, SJ and NM made substantial contributions to the acquisition, analysis and interpretation of data, drafting and revision of the work. This is the doctorate thesis of NM. VT, ML and AMM made substantial contributions to the acquisition and interpretation of data and drafting of the work. NBlank made substantial contributions to the conception, acquisition and interpretation of data, and revision of the work. BE, MG, SH, CN, CB and SU made substantial contributions to the acquisition and interpretation of data, and revision of the work. H-ML and EG made substantial contributions to the conception, acquisition, analysis and interpretation of data, revision of the work. NBenjamin made substantial contributions to the conception, acquisition, data analysis and interpretation of data, drafting and revision of the work. OD made substantial contributions to the conception, acquisition, analysis and interpretation of data, drafting and revision of the work. All authors read and approved the manuscript and agree to all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests PX has received personal fees from MSD and OMT. AM has received personal fees from Bayer, outside the submitted work. NBlank has received consulting fees, speaker fees and/or honoraria from MSD, GSK, Actelion and Bayer Vital. BE received travel fees, consulting fees, speaking fees and/or honoraria from Actelion, MSD, Bayer and OMT (less than $10 000 each). MG serves on an advisory Board for Bayer AG and receives lecture fees from Pfizer, MSD and Actelion Pharmaceuticals. SH has received personal fees from Bayer, MSD, Actelion and GSK, outside the submitted work. H-ML has received consulting fees, speaking fees and/or honoraria from AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca and Lilly (less than $10 000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm and Thermo Fisher. CN has received consulting fees, speaking fees and/or honoraria from Actelion, MSD, Boehringer, Novartis, Bayer and AstraZeneca (less than $10 000 each). CB received travel support from Actelion SA and Orpha Swiss and speakers’ fee from MSD. SU received grants from the Swiss National Science foundation and the Zurich Lung League, travel support and speakers’ fees from Actelion SA, Switzerland, Bayer SA, Germany, MSD, Switzerland and Orpha Swiss. EG has received grants and personal fees from Actelion, Bayer AG and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House (less than $10 000 each). NBenjamin received speaker fees from Actelion pharmaceuticals, Bayer HealthCare and MSD. OD has received grants and personal fees from research consultancies from AM, Acceleron Pharma, Amgen, AnaMar, Bayer, Beacon Discovery, Boehringer Ingelheim, Catenion, CSL Behring, ChemomAb, Ergonex, GSK, Inventiva, Italfarmaco, iQone, iQvia, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Blade Therapeutics, Glenmark Pharmaceuticals, Target Bio Science and UCB, outside the submitted work, to investigate potential treatments of scleroderma and its complications. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis issued (US8247389, EP2331143).
Patient consent for publication Not required.
Ethics approval The ethics committees of the Medical Faculty Heidelberg (S360/2009 and S231/2019) and Zurich (EUSTAR—database 839/BASEC Nr. 2016-01515 and cohort study BASEC-Nr. 2018-02165) had no objection against the conduct of the trial.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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