1049: Risk Stratification of Patients with Systemic Sclerosis-associated Pulmonary Arterial Hypertension in EUSTAR Using the Current and New Proposed Criteria

Hilde Jenssen Bjørkekjær¹, cosimo bruni², PATRICIA E CARREIRA³, Paolo Airò⁴, CARMEN PILAR SIMEON⁵, Marie-Elise Truchetet⁶, Alessandro Giollo⁷, Alexandra Balbir-Gurman⁸, Mickaël MARTIN⁹, Chris Denton¹⁰, Armando Gabrielli¹¹, Håvard Fretheim¹², Imon Barua¹², Helle Bitter¹³, Øyvind Midtvedt¹², Kaspar Broch¹⁴, Arne Andreassen¹², Yoshiya Tanaka¹⁵, Gabriela Riemekasten¹⁶, Ulf Müller-Ladner¹⁷, Marco Matucci-Cerinic², Ivan Castellvi¹⁸, Elise Siegert¹⁹, Eric Hachulla²⁰, Oliver Distler²¹ and Anna-Maria Hoffmann-Vold¹², ¹Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway, Kristiansand, Norway, ²University of Florence, Florence, Italy, ³HOSPITAL 12 DE OCTUBRE, Madrid, Spain, ⁴Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, Brescia, Italy, ⁵Hospital Vall D'Hebron, Barcelona, Spain, ⁶CHU de Bordeaux, Bordeaux, France, ⁷Rheumatology Section, Department of Medicine, University of Verona, Italy, Verona, Italy, ⁸Rheumatology Institute, Rambam Health Care Campus, Haifa, Israel, ⁹Poitiers's Universatory Hospital, Department of Internal Medicine, Poitiers, France, Mignaloux-Beauvoir, France, ¹⁰University College London, London, United Kingdom, ¹¹Università Politecnica delle Marche, Ancona, Italy, ¹²Oslo University Hospital, Oslo, Norway, ¹³Sorlandet sykehus, Kristiansand, Norway, ¹⁴Oslo University Hospital, Rikshospitalet, Department of Cardiology, Oslo, Norway, Oslo, Norway, ¹⁵University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ¹⁶University Clinic Schleswit-Holstein (UKSH), Luebeck, Germany, ¹⁷JLU Campus KK, Bad Nauheim, Germany, ¹⁸Hospital Universitari de la Santa Creu i Sant Pau, Vilafranca del Pened, Spain, ¹⁹Charité Hospital, Berlin, Germany, ²⁰University of Lille, LILLE, France, ²¹Department of Rheumatology, University Hospital Zurich, University of Zurich, Zürich, Switzerland

Background/Purpose: Pulmonary arterial hypertension (PAH) is a major clinical challenge in systemic sclerosis (SSc). A new definition for precapillary PH is proposed. Risk stratification is important for disease management, but is not validated in SSc-PAH and is not applied using the proposed criteria. We aimed to assess the performance of current risk stratification tools to estimate the 1- and 3- year mortality and to identify the best risk assessment approach in SSc-PAH.

Methods: We included all patients with newly diagnosed SSc-PAH according to the current and the proposed criteria from the European Scleroderma Trial and Research (EUSTAR) database from 2001 to 2021. The current criteria define PAH as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg, while the proposed criteria use mPAP >20 mmHg; a pulmonary artery wedge pressure ≤15 mmHg, and a pulmonary vascular resistance ≥3 Wood units in the absence of significant interstitial lung disease. We applied four different approaches for risk stratification at time of diagnosis including parameters according to the 2015 ESC/ERS Guidelines (Table).

1: Patients with ≥ 1 high-risk parameter were considered at high risk; ≥ 1 intermediate-risk parameter at intermediate risk, otherwise at low risk
2: Each parameter was graded from 1 to 3 representing low to high risk. The mean of available risk parameters was rounded to the nearest integer to define the risk category
3: Equals Model 2, but the intermediate risk group was divided into intermediate-low and intermediate-high based on the mean score
4: Stratifies patients into four risk categories based on the proportion of low-risk parameters

We used descriptive statistics and performed analysis of 1- and 3- year mortality in patients with a minimum follow-up of 1 and 3 years, respectively.

Results: Of 902 patients who conducted RHC, 271 (30%) were diagnosed with SSc-PAH according to the current criteria and an additional 36 (4%) according to the proposed criteria (Table).

Patients diagnosed according to the proposed criteria were diagnosed at a lower risk level compared with patients with PAH according to the current criteria (Figure 1).

For the current PAH criteria, the 1- and 3-year mortality was 10% and 31%. The models varied in their ability to estimate mortality (Figure 2). Models 1 and 4 either over- or underestimated mortality. Model 2 stratified patients according to the expected 1-year mortality of < 5%, 5-10% and >10% as suggested by the Guidelines. Model 3 segregated the mortality further within the intermediate-risk group.

For the patients who fulfilled the proposed PAH criteria, but not the current criteria, the 1- and 3-year mortality was 0% and 18%. The risk stratification models estimated mortality poorly, possibly due to the small sample size.

Conclusion: Models 2 and 3 seem to be well suited and provide signals for a better risk stratification of patients with newly diagnosed SSc-PAH according to the current criteria, with Model 3 further segregating the mortality in the intermediate-risk group. The patients who fulfilled the proposed PAH criteria, but not the established criteria, were on average diagnosed at a lower risk level, but the 3-year mortality is still high. This may provide guidance for optimized management in clinical practice.
Figure 1:  Proportion of patients in each risk category at baseline segregated by the different models

Figure 2:  1- and 3-year mortality according to risk category in the four different models in patients with a minimum follow-up of 1 and 3 years, respectively

Table: Demographic and clinical characteristics at baseline of patients with PAH diagnosed according to the current and the proposed criteria.

lcSSc: limited cutaneous systemic sclerosis; NYHA: New York Heart Association functional class; 6MWD: 6 minute walk distance; RA area: Right atrial area; RHC: Right heart catheterization; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance
Disclosures: H. Bjørkekjær, None; C. Bruni, Boehringer-Ingelheim, Eli Lilly; P. CARREIRA, None; P. Airò, Bristol-Myers-Squibb, Boehringer Ingelheim, Roche, Jannsen, CSL Behring; C. SIMEON, Merck/MSD, Janssen, Boehringer-Ingelheim; M. Truchetet, AbbVie/Abbott, Galapagos, Eli Lilly, Medac, Novartis, Pfizer, Roche; A. Giollo, None; A. Balbir-Gurman, None; M. MARTIN, None; C. Denton, Boehringer-Ingelheim, Roche, GlaxoSmithKlein(GSK), Horizon; A. Gabrielli, None; H. Fretheim, Bayer, GSK and Actelion; I. Barua, None; H. Bitter, Boehringer-Ingelheim; Ø. Midtvedt, Jannsen, Boehringer-Ingelheim; K. Broch, AstraZeneca, Bayer, Pfizer, Pharmacosmos, Vifor Pharma; A. Andreassen, Jannsen; Y. Tanaka, Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, Taisho Toyama, Celltrion, Gilead, Boehringer-Ingelheim, Corrona, Kowa, Amgen, AstraZeneca, AstraZeneca, Eli Lilly; G. Riemekasten, Boehringer Ingelheim; U. Müller-Ladner, Biogen; M. Matucci-Cerinic, Biogen, Eli Lilly, Chemomab, Sandoz, Merck/MSD, Pfizer, Behring, Janssen; I. Castellvi, None; E. Siegert, None; E. Hachulla, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, CSL Behring, Bayer, Boehringer Ingelheim, Sanofi-Genzyme; O. Distler, AbbVie/Abbott, Amgen, GlaxoSmithKlein(GSK), Novartis, Roche, UCB, Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, 4P-Pharma, Acceleron, Alcimed, Altavant Sciences, AnaMar, Arxx, AstraZeneca, Blade Therapeutics, Bayer, Corbus Pharmaceuticals, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Lupin, Miltenyi Biotec, Merck/MSD, Prometheus Biosciences, Redx Pharma, Roivant, Sanofi, Topadur, Pfizer, Janssen, Medscape, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143), FOREUM Foundation, ERS/EULAR Guidelines, EUSTAR, SCQM (Swiss Clinical Quality Management in Rheumatic Diseases), Swiss Academy of Medical Sciences (SAMW), Hartmann Müller Foundation; A. Hoffmann-Vold, Boehringer-Ingelheim, Janssen, Eli Lilly, Merck/MSD, Roche.