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

Study Questions:

The ST2 receptor is a member of the toll-like/interleukin-1 receptor family and may be involved in cardioprotective stress-response signaling. Soluble ST2 is predictive of adverse outcomes in acute heart failure (HF), but does ST2 predict chronic HF outcomes?


The association between ST2 levels and transplant-free survival in 1,141 subjects with chronic HF was evaluated. Cox hazard ratios were calculated, and the predictive ability of ST2 was compared with N-terminal portion of probrain natriuretic peptide (NT-proBNP) and the Seattle Heart Failure model (SHFM) using receiver operating characteristic (ROC) curves.


The mean ± standard deviation patient age was 56 ± 14 years, 67% were male, and 87% had systolic HF (86% were New York Heart Association class II or III) with a mean left ventricular ejection fraction of 32 ± 17%. Median NT-proBNP levels were 567 and the mean SHFM score was 0.25 ± 1.0. Over 2.78 years of follow-up, there were 160 deaths and 107 transplantations. Compared with the lowest tertile, patients in the highest ST2 tertile (ST2 >36.2 ng/ml) had a 3.2 (95% confidence interval [CI], 2.2-4.7) higher unadjusted hazard ratio for death/transplantation. On a continuous scale, each doubling of ST2 was associated with an adjusted 40-50% increased odds of death/transplantation. The area under the ROC curve for ST2 in predicting death/transplantation was 0.75 (95% CI, 0.69-0.79), which was similar to that of NT-proBNP (AUC = 0.77; 95% CI, 0.072-0.81; p = 0.24), but inferior to the SHFM (AUC = 0.81; 95% CI, 0.77-0.85; p = 0.014). The addition of ST2 and NT-proBNP to the SHFM improved the risk stratification of 14.9% of patients compared with the SHFM alone (p = 0.017), but this effect was not noted when ST2 was added to a model containing the SHFM and NT-proBNP.


The authors concluded that ST2 is prognostic of poor outcome in patients with chronic HF.


Prognosticating outcome in HF is important for both patient and family education as well as for determining optimal timing for transplant or left ventricular assist device (LVAD) in those eligible. The authors demonstrate that ST2 levels are predictive of adverse outcome in HF. While the association between ST2 level and adverse outcome was nearly linear, outcomes were especially poor in the early- and long-term for the 379 patients with an ST2 >36.3. With the known limitations of the SHFM in cohorts with very advanced HF, the addition of the ST2 to the SHFM may improve HF prognostication and candidate selection for transplant/LVAD. ST2 may be especially useful for those patients in whom NT-proBNP may not accurately reflect HF severity (e.g., renal failure, obesity).

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Mechanical Circulatory Support

Keywords: Follow-Up Studies, Biological Markers, Heart-Assist Devices, Heart Failure, Receptors, Interleukin-1, Stroke Volume, Obesity, New York

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