Galectin-3 in Ambulatory Patients With Heart Failure: Results From the HF-ACTION Study

Study Questions:

What is the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure (HF) patients?

Methods:

The study cohort was comprised of 895 HF patients from the HF-ACTION study, which was a randomized controlled trial of exercise training in chronic HF patients due to left ventricular systolic dysfunction. The investigators compared galectin-3 at baseline from stored plasma samples available, with clinical outcomes using a series of Cox proportional hazards models.

Results:

The investigators found that higher galectin-3 levels were associated with measures of HF severity, including higher New York Heart Association class, lower systolic blood pressure, higher serum creatinine, higher N-terminal pro–B-type natriuretic peptide (NT-proBNP), and lower maximal oxygen consumption. They found that there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio = 1.14 per 3 ng/ml increase in galectin-3, p < 0.0001) in the unadjusted analysis. But in multivariable modeling, the prognostic impact of galectin-3 was significantly diminished by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NT-proBNP.

Conclusions:

They concluded that galectin-3 is elevated in ambulatory HF patients and is associated with poor functional capacity and other known measures of HF severity. In the univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NT-proBNP.

Perspective:

This is an important study because it suggests that biomarkers must be measured judiciously in the evaluation of risk in HF (Heart Fail Clin 2009;5:ix-xii). An earlier small study (the Pro-BNP Investigation of Dyspnea in the Emergency Department study) suggested that the combination of galectin-3 and NT-proBNP provides incremental prognostic information for short-term death in acute HF (J Am Coll Cardiol 2006;48:1217-24). The current study was a larger cohort, but was comprised of more stable HF patients. Further studies are needed to determine whether the value of galectin-3, in risk stratification of HF, is limited to acute decompensated HF.

Keywords: Macrophages, Exercise, Blood Pressure, Creatinine, Galectin 3, New York, Dyspnea, Heart Diseases, Prognosis, Proportional Hazards Models, Biomarkers, Oxygen Consumption, Heart Failure, Ventricular Dysfunction, Left, Natriuretic Peptide, Brain


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