Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare form of pulmonary hypertension (PH) that may also be associated with connective tissue diseases (CTD). In particular, PAH may affect from 5 to 19% of patients with systemic sclerosis (SSc), leading to a significant prognostic worsening. The current challenge is an early detection of PAH in such patients, in order to provide an early referral to PH centers to supply specific therapies as soon as possible. In the latest ESC guidelines for PH, cardiopulmonary exercise testing (CPET) has been included in the diagnostic algorithm for patients with unexplained exertional dyspnoea and/or suspected PH. Patients with PAH show a typical pattern, with a low end-tidal partial pressure of carbon dioxide (PETCO2), high ventilatory equivalent for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/ HR) and low peak oxygen uptake (VO2). CPET may identify patients with SSc at low risk of PAH, to avoid unnecessary right heart catheterization (RHC). However, CPET is not available in all centers. So, we designed a preliminary study to identify new biomarkers that correlate with CPET's parameters. Material and Methods We enrolled 62 SSc patients [53 females, median age 52 years] with no other comorbidities and asymptomatic for dyspnea or other symptoms. 56% and 44% of them presented limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), respectively. For all patients we performed serum analysis for sST2, Galectine-3, pro-ANP, BNP and IL6, diagnostic imaging with echocardiography and cardiac MRI, CPET and pulmonary functionality test (PFT). Results All patients presented normal echocardiographic and RMI imaging findings. Galectin-3, sST2, pro-ANP, BNP and IL6 presented respectively the following median value: 13.45 ng/mL [11.78; 18.70], 23.25 ng/mL [13.04; 43.35], 1897 fmol/ml [1487; 2445], 12.18 pg/mL [9.34; 15.01]. Both Galectin-3 and sST2 showed a linear correlation with VE/VCO2 slope with R 0.339 (P-value 0.018) and 0.355 (P-value 0.013) respectively. After linear regression analysis, Galectin-3 and sST2 were overall statistically significant with R2 of 0.115 and 0.126, F of 5.97 and 6.62 and P-value of 0.018 and 0.013, respectively. It was found that Galectin-3 and SST2 significantly predicted VE/VCO2 slope with β = 0.364 [0,064; 0,665] for Galectin-3 and 0.137 [0,030; 0,244] for SST2. All other CPET parameters did not show correlation with the biomarkers. Conclusion Our preliminary results suggest that Galectine-3 and sST2 may be useful biomarkers for predicting increasing VE/VCO2 slope. Future analysis may confirm the role of these new biomarkers for early detection of pulmonary vascular involvement in SSc patients to allow an early referral and treatment and, conversely, to avoid unnecessary RHC.
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