The mortality implications of increasing and decreasing sST2 levels during acute decompensated heart failure
Authors: Li B , Dowley M , Langley S , Cliffe P , Whiting S , Zydzik L , Dimarco A , Barbagallo R , Dungu J N , Savage H O 
Published: October 2024

Abstract

Introduction
Soluble Suppressor of Tumorigenicity (sST2), a marker of cardiac remodelling and fibrosis, has demonstrated promises in prognostication of heart failure (HF) and therefore recommended as an additional test for risk stratification of HF in the 2017 ACC/AHA/HFSA guidance. It is well investigated as single measurements in acute and ambulatory settings. Data regarding sST2 level changes during acute decompensated heart failure (ADHF) and its potential in providing additional prognostic information is however sparse. We therefore sought to evaluate changes in sST2 and its prognostic implications in hospitalized patients during ADHF.

Methods
Between December 2019 and February 2022, consecutive patients with ADHF and reduced ejection fraction (EF&lt;50%) presenting to our University Hospital were recruited as part of the Investigating the soluble ST2 biomarker in addition to Natriuretic peptides in managing patients with Heart Failure and a Reduced Ejection Fraction (INST2ANT-HF) study (REC Reference: 19/EE/0269). Serum samples were taken at clinician determined decompensation and recompensation in all participants, who were then followed up for one year post discharge. The study primary end point was all-cause mortality at one year. A 2x2 contingency table was constructed to display the relationship between the frequency of unchanged/increased or decreased sST2 levels at recompensation and the frequency of mortality at one year (Table 1). A Kaplan-Meier curve was plotted to display the survival probability of the two groups during one-year follow up (Figure 1), and log-rank test applied to evaluate for significant difference in the survival distributions.

Results
In 169 patients with paired sST2 samples, median age (IQR) was 72 (62-80.8), 39 (23.2%) were female and 160 (95.2%) were ethnically white. 158 (94.1%) presented with NYHA class II-IV and the median (IQR) EF was 26% (17.5-32.5). Median (IQR) length of stay in hospital was 8 days (5-13). Median (IQR) sST2 level at decompensation and recompensation were 60ng/ml (40-93.3) and 39.5ng/ml (24-64.8) respectively. At clinician determined recompensation, sST2 level decreased in 136 (81%) patients while 32 (19%) had unchanged/increased sST2 levels. One-year mortality was 37.5% in patients with unchanged or increasing sST2 levels during ADHF, compared to 16.2% in those with decreased sST2 levels. The mean (SE) survival time was 332 (7) days for patients with unchanged/increasing sST2, and 274 (22.5) days for patients with decreasing sST2 at HF recompensation (p=0.003).

Conclusion
Our data demonstrates that there was a downward trend in sST2 in most patients during recovery from an ADHF episode. Importantly, a static or increasing sST2 level from HF decompensation to recompensation was associated with a significantly higher risk of mortality at one year. Further research may ascertain if the mortality risk is also dependent on the percentage changes in sST2 concentrations.Table 1:2x2 contingency tableFigure 1:Kaplan-Meier curve