VE/VCO2 at ventilatory threshold and peak VO2 in CPET studies of patients with scleroderma-associated PAH: A systematic review and meta-analyses

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Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in patients with systemic sclerosis (SSc). Cardiopulmonary exercise testing (CPET) has been studied to detect SSc-associated PAH. To evaluate the diagnostic value of the ventilatory equivalent for CO 2 at anaerobic or ventilatory threshold [VE/VCO 2 (VeT)] and peak oxygen uptake (peak VO 2 ) for SSc-associated PAH obtained by CPET. A systematic database search from 1993 to 2024 and meta-analyses were performed according to PRISMA guidelines to include original studies relating to SSc and CPET reporting VE/VCO 2 (VeT) and peak VO 2 . The random-effects model was chosen for the meta-analyses studying VE/VCO 2 (VeT), indexed and predicted percentage (%pred.) peak VO 2 , respectively. Meta-regression was only performed for VE/VCO 2 (VeT) with covariates defined as the percentage of limited cutaneous disease, percentage of interstitial lung disease, and %pred. of peak VO 2 . Out of 206 studies, 941 SSc patients from 15 studies were included. VE/VCO 2 (VeT) (11 studies, n = 850) was statistically lower in patients without PAH (32.68 ± 5.42 vs. 39.81 ± 9.32) with a mean effect size of −1.182 (95 %CI, −1.691 to −0.672; p < 0.001) (I 2 = 86 %). The mean effect size for weight-indexed peak VO 2 (11 studies, n = 848) was 0.713 (95 %CI, 0.371 to 1.054; p < 0.001) with higher values in patients without PAH (16.47 ± 4.62 vs. 13.61 ± 4.16 mL/kg/mn) (I 2 = 70 %). Similarly, the mean effect size for %pred. Peak VO 2 (12 studies, n = 850) was 0.659 (95 %CI, 0.425 to 0.894; p < 0.001) reflecting higher values in patients without PAH (74.00 ± 17.50 vs. 54.84 ± 18.14 %pred.) (I 2 = 37 %). Meta-regression analysis of data from 7 studies did not yield significant p values for the covariates. The effect size of each meta-analysis indicates that higher VE/VCO 2 (VeT) and lower peak VO 2 may be considered as independent CPET markers of PAH in patients with SSc. CPET is a non-invasive and safe procedure for exploring dyspnoea in patients with SSc and, in association with conventional imaging techniques, may provide a reliable assessment of the presence of PAH. • CPET is a non-invasive and safe procedure for detecting PAH in patients with SSc. • Patients with SSc-associated PAH have higher VE/VCO 2 (VeT). • Those without PAH have significantly higher peak VO 2 .

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