Soluble ST2 in Ambulatory Patients With Heart Failure: Association With Functional Capacity and Long-Term Outcomes

Study Questions:

What is the role of ST2 in patients with ambulatory heart failure?


ST2, a novel cardiac biomarker used in patients with heart failure, was evaluated in patients to assess long-term clinical outcomes in patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study. HF-ACTION was a study that assessed the effects of exercise training versus usual care on long-term morbidity and mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. A subset of patients who enrolled in HF-ACTION agreed to participate in a biomarker study with assays collected at baseline, 3 months, and 12 months after enrollment. Blood samples were collected the same day as baseline cardiopulmonary exercise testing, but prior to exercise.


A total of 910 patients were included in this study, who were stratified by ST2 levels greater than and less than 35 ng/ml. The median age of the study was 59 years, and 71% were male. The median left ventricular ejection fraction was 24% and the majority of patients were on guidelines-based medical therapy for systolic heart failure. The median baseline ST2 level was 23.7 ng/ml (interquartile range, 18.6-31.8). Patients with ST2 levels >35 ng/ml were more likely to be men and to have markers of more advanced disease, such as worse functional class, worse renal function, and higher levels of N-terminal pro–B-type natriuretic peptide (p < 0.001 for all). Univariable analysis did demonstrate that ST2 was significantly associated with death or hospitalization (hazard ratio [HR], 1.48; p < 0.001), cardiovascular death or heart failure hospitalization (HR, 2.14; p <0.001), and all-cause mortality (HR, 2.33; p < 0.001). Multivariable analysis did not demonstrate that ST2 could be added to reclassify risk.


The authors concluded that elevation of ST2 was significantly associated with long-term outcomes such as cardiovascular death and heart failure hospitalization. ST2 did not add significantly to risk prediction in this subset of patients.


Biomarkers are playing a more important role in risk stratification of heart failure patients. ST2 will be a marker that we can expect to see more of in larger studies to further define its role in chronic heart failure patients.

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

Keywords: Heart Diseases, Natriuretic Peptides, Risk, Ventricular Dysfunction, Biological Markers, Health Resources, Troponin I, Cardiology, Heart Failure, Peptide Fragments, Stroke Volume, Exercise Test

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