Investigating the soluble suppressor of tumorigenicity 2 biomarker in addition to natriuretic peptides in managing patients with heart failure and a reduced ejection fraction

Introduction: Soluble suppressor of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family that has been suggested as a biomarker for prognostication and risk stratification in heart failure (HF). Although prognostic capability and threshold levels are established in chronic HF, the utility of sST2 as repeated measurements linked to HF statuses during acute HF is currently unknown. This study aimed to investigate sST2 in addition to natriuretic peptides in patients with heart failure with reduced ejection fraction.

Methods: Between December 2019 and January 2022, consecutive patients admitted to Basildon University Hospital for acute decompensated HF with reduced ejection fraction (LVEF<50%) were consented to participate in Investigating the soluble ST2 biomarker in addition to Natriuretic peptides in managing patients with Heart Failure and a Reduced Ejection Fraction (INST2ANT-HF) study. All recruited participants had blood samples collected for sST2 and natriuretic peptide within 24 hours of HF decompensation and recompensation, and followed up for one year post discharge for adverse events. The study hypothesis was that there is an interval change in sST2 between a period of decompensated HF and a period of recompensation.

Results: In the 168 patients with paired sST2 samples, a median reduction of 32.3% (95% CI 9.6 - 53.6) in sST2 level was detected between HF decompensation and recompensation (p<0.001). A lower sST2 reduction between the HF statuses was observed in the group that reached the composite outcome of all-cause mortality and rehospitalisation at one year (-24.5% (IQR -44.8 to +8.7) vs -38.4% (IQR -58.6 to -16.4), p=0.026). sST2 reduction of 37.3% was found to be a significant independent threshold for prediction of the composite outcome at one year after multivariate adjustments, with risks doubled if sST2 does not fall by 37.3% upon HF recompensation (p=0.027). Head-to-head comparison with NT-proBNP demonstrated no significant prognostic advantage of one biomarker over the other, but sST2 displayed better stability in renal impairment.

Conclusion: The present study demonstrated that there is a significant reduction in sST2 levels between HF decompensation and recompensation, which has significant prognostic capability independent of NT-proBNP and therefore provides additive value in management of HF patients. Future research should explore the practical clinical utility of sST2 changes in monitoring and guiding treatment of HF.