Head-to-Head Comparison of Two Myocardial Fibrosis Biomarkers for Long-Term Heart Failure Risk Stratification: ST2 vs. Galectin-3

Study Questions:

What is the prognostic value of high-sensitivity ST2 (ST2) and galectin-3 (Gal-3), novel biomarkers predictive of ventricular remodeling and fibrosis, in an ambulatory heart failure (HF) population?


This was a cohort study of 876 ambulatory patients (median age 70 years, median left ventricular ejection fraction [LVEF] 34%) treated at a multidisciplinary HF unit from May 2006 to July 2010. ST2 and Gal-3 were evaluated relative to clinical risk factors (age, sex, New York Heart Association functional class, estimated glomerular filtration rate, LVEF, diabetes mellitus, sodium, hemoglobin, ischemic etiology of HF, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker treatment, and beta-blocker treatment) plus serum N-terminal pro–B-type natriuretic peptide (NT-proBNP). The incremental prognostic value of ST2 and Gal-3 was evaluated in terms of discrimination, calibration, and reclassification analysis. Primary endpoints were 5-year all-cause and cardiovascular death and the combined all-cause death or HF hospitalization.


In multivariate analysis, only ST2 remained independently associated with cardiovascular mortality (hazard ratio, 1.27; 95% confidence interval, 1.05-1.53; p = 0.014). While incorporation of ST2 into an adjusted model for all-cause mortality improved discrimination and calibration and reclassified significantly better, this was not the case with Gal-3.


In a population of ambulatory HF patients, both ST2 and Gal-2 were associated with an increased risk of all-cause mortality, but only ST2 was associated with cardiovascular mortality and only ST2 added incremental predictive ability to existing risk factors.


The limitations of the this analysis aside, this head-to-head comparison of two fibrosis biomarkers establishes that ST2 is predictive of both all-cause and cardiovascular mortality, and may have a role refining risk stratification in clinical practice. Future studies are needed. The incremental predictive value of adding Gal-3 to existing clinical risk factors is probably marginal, and, as the authors suggest, Gal-3 may be a ‘systemic biomarker rather than specific to HF.’

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

Keywords: Biological Markers, Membrane Proteins, Heart Failure, Ventricular Remodeling, Risk Factors, Glomerular Filtration Rate, Galectin 3, Fibrosis, Natriuretic Peptide, Brain

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