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This study aimed to assess the predictive effect of soluble ST2 (sST2) and depressive symptoms in patients with heart failure (HF) and to determine whether the prognosis of HF patients with preserved ejection fraction (HFpEF) differs from those with reduced ejection fraction (HFrEF). A cohort of 233 HF patients was followed for 1 year. Depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale. The primary endpoint was all-cause mortality and HF-related hospitalization. For the analysis of survival, the left ventricular ejection fraction (LVEF) cut-offs for defining HFpEF were set at 50%, 45%, and 40%, respectively. With increasing LVEF, levels of sST2 were gradually decreased (45.2 ng/mL, 35.8 ng/mL, and 32.1 ng/mL in patients with LVEF ≤ 40%, 41% to 49%, and ≥ 50%, respectively, P for trend < 0.001), as well as the prevalence of depressive symptoms (35.4%, 33.3%, and 20.4%, respectively, P for trend = 0.022). After 1-year follow-up, 128 patients (54.9%) achieved the primary endpoint and 47 patients (20.2%) died. Depressive symptoms were independent risk factors of all-cause mortality and HF-related hospitalization. The combined presence of elevated sST2 (> 36.0 ng/mL) and depressive symptoms was associated with a 4.9-fold increased risk of the primary endpoint. Regardless of LVEF cut-offs, the associated risk of adverse outcomes in HFpEF was as high as in HFrEF after adjustment for significant risk factors including sST2 and N-terminal pro-brain natriuretic peptide. In conclusion, depressive symptoms provided additional prognostic information to that of sST2 in HF patients. The prognosis of HFpEF patients was similar to that of HFrEF patients.

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