Soluble ST2 in Heart Failure: A Clinical Role beyond B-Type Natriuretic Peptide

Abstract

Soluble (s)ST2 has been proposed as a useful biomarker for heart failure (HF) patient management. Myocardial damage or mechanical stress stimulate sST2 release. ST2 competes with a membrane bound receptor (ST2 ligand, or ST2L) for interleukin-33 (IL-33) binding, inhibiting the effects induced by the ST2L/IL-33 interaction so that excessive sST2 may contribute to myocardial fibrosis and ventricular remodeling. Compared to natriuretic peptides (NPs), sST2 concentration is not substantially affected by age, sex, body mass index, kidney function, atrial fibrillation, anemia, or HF etiology, and has low intra-individual variation. Its prognostic role as an independent marker is well reported in the literature. However, there is a gap on its use in combination with NPs, currently the only biomarkers recommended by European and American guidelines for HF management. Reflecting the activation of two distinct biological systems, a benefit from the use of sST2 and NP in combination is advocated. The aim of this review is to report the current scientific knowledge on sST2 in the acute and chronic HF settings with a particular attention to its additive role to natriuretic peptides (NPs).

Keywords: heart failure; natriuretic peptides; solubleST2.

Figure 1

Pathological role of sST2 in promoting fibrosis and ventricular remodeling.

Figure 2

Current evidence on the role of sST2 in HF patients. * Not directly influenced by age, sex, BMI, kidney function, AF, anemia or HF etiology, and it has a low intra-individual variation. Forest plot analysis showing hazard ratios and 95% confidence interval of sST2 and mortality in acute and chronic HF settings (adapted from J Am Coll Cardiol HF 2017; 5:280–6; and J Am Coll Cardiol HF 2017; 5:287–96) [52,81].