High-Sensitivity ST2 for Prediction of Adverse Outcomes in Chronic Heart Failure

Study Questions:

Do plasma levels of ST2 independently predict outcomes in patients with chronic heart failure (CHF)?

Methods:

The association between ST2 levels and risk of death or transplantation in a multicenter, prospective cohort of 1,141 CHF outpatients was determined. Adjusted Cox models, receiver operating characteristic analyses, and risk reclassification metrics were used to assess the value of ST2 in predicting risk beyond currently used factors.

Results:

After a median of 2.8 years, 23% of patients died or underwent heart transplantation. Patients in the highest ST2 tertile (ST2 >36.3 ng/ml) had a markedly increased risk of adverse outcomes compared with the lowest tertile (ST2 ≤22.3 ng/ml), with an unadjusted hazard ratio of 3.2 (p < 0.0001) that remained significant after multivariable adjustment (adjusted hazard ratio, 1.9; 95% confidence interval, 1.3-2.9; p = 0.002). Addition of ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to the Seattle Heart Failure Model reclassified 14.9% of patients into more appropriate risk categories (p = 0.017).

Conclusions:

The authors concluded that ST2 is a potent marker of risk in CHF, and when used in combination with NT-proBNP, offers moderate improvement in assessing prognosis beyond clinical risk scores.

Perspective:

A soluble form of ST2 is found in the circulation that lacks intracellular and transmembrane domains. Thus, sST2 may act as a decoy receptor that interferes with cardioprotective cellular signaling via its ligand, IL-33. Previous studies have shown that ST2 levels are associated with left ventricular dysfunction and neurohormonal activation following acute myocardial infarction. The current study adds to these findings by showing that sST2 levels may also be useful to predict prognosis in patients with CHF. These findings may provide insight into the underlying pathophysiology of progressive HF that could guide further management. However, the clinical utility of sST2 measurements in CHF patients remains to be determined.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Myocardial Infarction, Biological Markers, Heart Failure, Peptide Fragments, Ventricular Dysfunction, Left, Natriuretic Peptide, Brain


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