Abstract
Soluble ST2 (sST2) has emerged as a powerful prognostic marker in chronic systolic heart failure with reduced ejection fraction (HFrEF). Elevated levels of sST2 are associated with adverse cardiac remodeling and fibrosis. However, few studies have demonstrated the relative prognostic value of sST2 collected from stable patients in the ambulatory setting and correlated it with long term clinical outcomes.
In our study, we sought to determine the prognostic utility of a baseline sST2 partition value in the ambulatory setting as it related to subsequent risk for heart failure hospitalization and all-cause mortality.
Single-center, retrospective observational study of subjects presenting to an ambulatory heart failure (HF) clinic from July 2014 to December 2016. There were 156 subjects with stage C heart failure and a baseline sST2 level. For purposes of this analysis in HFrEF, we excluded patients with EF > 40% resulting in a study cohort of 103 subjects. The mean follow-up was 2.20 years ± 1.53 years. Analysis was performed with IBM SPSS Statistics 26 software package. Discrete variables were expressed as counts (percentage) and were compared using the Chi-squared test. Mean differences of continuous variables were expressed as a mean ± standard deviation and compared using the unpaired Student's t-test. The log-rank test (Mantel-Cox) was used to compare survival times on Kaplan-Meier curves. To determine the diagnostic and prognostic accuracies of sST2 and BNP, receiver operating characteristic (ROC) plots were analyzed, and areas under the curve (AUC) were calculated.
Patients who had baseline sST2 ≥ 35 ng/ml were at increased risk for heart failure hospitalization and all-cause mortality compared to patients who had sST2 < 35 ng/ml. Patients with sST2 ≥ 35 ng/ml had a mean of 1.76 HF hospitalizations, 44.0% of this group had ≥ 2 HF hospitalizations and 50.0% all-cause mortality. Patients with sST2 < 35 ng/ml had a mean of 0.80 HF hospitalizations, 15.0% had ≥ 2 HF hospitalizations and 18.0% all-cause mortality. We also found that sST2 ≥ 35 ng/ml was associated with increased risk for atrial arrhythmias (39.0% vs. 20.5%), lower hemoglobin (11.5 vs 13.0), and lower systolic blood pressure (109.6 vs 124.8).
Subjects with sST2 levels ≥ 35 ng/ml were at increased risk of recurrent hospitalization and all-cause mortality. Additionally, we saw that elevated sST2 was associated with increased atrial arrhythmia, hypotension, and anemia. The results of this study highlight the value of sST2 concentrations as a prognostic biomarker for identifying patients with HFrEF that are at increased risk for morbidity and mortality in the ambulatory setting.
Key words: Soluble ST2, cardiac remodeling, biomarkers, heart failure