Clinical value of soluble suppression of tumourigenicity 2 (sST2) in addition to NTproBNP measurements in a general cardiac outpatient population

Abstract

BACKGROUND AND AIMS: The soluble form of suppression of tumourigenicity 2 (sST2), a recently introduced biomarker, is a strong and NTproBNP-independent predictor of outcome in heart failure patients. This study sought to evaluate the added clinical value of sST2 in addition to NTproBNP in a heterogeneous cardiac outpatient population. METHODS: A total of 297 all-comer patients visiting the outpatient clinic of Heart Clinic Zurich, Switzerland, from January to December 2018 were included. Patients were divided into four groups depending on their sST2 and NTproBNP levels: group 1 (n = 91, 30.6% of all patients) with normal levels of both biomarkers, group 2 (n = 41, 13.8%) with isolated elevation of sST2 but normal NTproBNP, group 3 (n = 97, 32.7%) with elevated NTproBNP but normal sST2 levels, and group 4 (n = 68, 22.9%) with elevation of both biomarkers. Differences between groups, Spearman’s correlations and linear and multiple regression analysis for sST2 were calculated. RESULTS: The median age was 74 ± 19 years and 41.8% were women. NTproBNP levels continuously increased across the groups (medians in pg/ml: group 1 123.0, group 2 152.0, group 3 990.0 and group 4 2610.0), whereas sST2 levels did not (medians in ng/ml: 28.7, 58.9, 28.4 and 63.7 for groups 1 to 4, respectively). In patients with normal NTproBNP (groups 1 and 2), elevation of sST2 (group 2) was associated with significantly higher rates of coronary artery disease, peripheral vascular disease and renal dysfunction. In patients with elevated NTproBNP (groups 3 and 4), the additional elevation of sST2 (group 4) was associated with clinical signs of heart failure, higher EuroScore II and worse left ventricular ejection fraction (LVEF group 3 58.0% vs group 4 53.3%, p = 0.022). Correlation of sST2 was overall weak and weaker than of NTproBNP with most clinical variables. Soluble ST2 significantly correlated with EuroScore II (R = 0.280), kidney function (R = −0.259), C-reactive protein (R = 0.248), right ventricular function (R = 0.213) and left atrial volume (R = 0.199), all p ≤0.001. In multiple regression analysis, left atrial volume was the strongest independent predictor of sST2 elevation (p = 0.002). CONCLUSION: In this all-comer cardiology population, the added clinical value of sST2 measurements in addition to NTproBNP was small. In patients with elevated NTproBNP, the simultaneous elevation of sST2 was associated with clinical signs of heart failure. Soluble ST2 measurements could thus be beneficial in patients with uncertain signs of heart failure and confounding factors for NTproBNP elevation. Surprisingly, this study found elevated sST2 levels in a substantial number of a patients with normal NTproBNP levels, pointing to an additional pathway of sST2 elevation independent of heart failure.