Prognostic value of baseline and changes in circulating soluble ST2 levels and the effects of nesiritide in acute decompensated heart failure

Objectives: The study sought to investigate the association between soluble growth stimulation expressed gene 2 (sST2) level and adverse outcomes in acute heart failure (HF). Background: Several studies have demonstrated the prognostic utility of sST2 levels in HF. Methods: sST2 levels were measured in sequential baseline and follow-up (48 to 72 h and 30 days) plasma samples from 858 acute HF subjects enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial biomarker substudy and were related to in-hospital and post-discharge clinical outcomes. Results: Higher sST2 levels were associated with increased death risk at 180 days (baseline hazard ratio [HR]: 2.21; follow-up HR: 2.64; both p < 0.001). These results were not independent of covariates and aminoterminal pro-B-type natriuretic peptide for baseline sST2 (HR: 1.29, p = 0.243), but were borderline significant for follow-up sST2 (HR: 1.61, p = 0.051). Subjects with persistently high (>60 ng/ml) sST2 levels at follow-up had higher 180-day death rates than those with lower follow-up sST2 levels (adjusted HR: 2.91, p = 0.004). Neither baseline nor follow-up sST2 levels were associated with dyspnea improvement. Changes in sST2 from baseline were less in the nesiritide versus placebo group at follow-up, but were similar at 30 days. Conclusions: Elevated levels of sST2 were associated with an increased risk of adverse clinical events in acute HF, but prognostic value of baseline sST2 diminished after adjusting for clinical covariates and aminoterminal pro-B-type natriuretic peptide. In those with elevated baseline sST2 levels, persistently elevated sST2 levels at follow-up were associated with increased mortality risk. In addition, nesiritide did not demonstrate an incremental impact on sST2 levels over standard therapy.