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Galectin-3 in Chronic Heart Failure

Measuring galectin-3 in patients with chronic heart failure will provide health care providers  and patients with more information about the prospects for the outcome of the disease. This information will support a range of decisions that health care providers and patients need to make. The ultimate goal is to find specific treatments that work best in patients with high galectin-3 levels. For the time being, there are many things that health care providers can potentially do when they learn that a patient has elevated levels of galectin-3, including, for example, more frequent follow-up visits because of the increase risk of hospitalizations, and assuring compliance with treatment guidelines pertaining to the use of medial treatment, including aldosterone antagonists.

Results of studies focused on galectin-3 in heart failure have been very consistent. Below are some of the findings from studies BG Medicine has sponsored, as well as studies published in peer-reviewed publications. This information reflects our current knowledge and understanding.

Prevalence of elevated galectin-3 (>17.8 ng/mL) in patients with HF:

  1. Elevated galectin-3 is relatively common affecting around 30% in a NYHA class II/III outpatient population.
  2. When measured in patients with chronic heart failure who were admitted for decompensated heart failure, the proportion of elevated galectin-3 is much higher—around 65% (sample taken after resolution of acute decompensation). Patients with low galectin-3 values have a lower risk of heart failure hospitalizations. Consequently, when patients are recruited from an in-patient facility, the higher proportion of galectin-3 elevation is affected by selection bias.
  3. The proportion of patients with elevated galectin-3 increases with increasing severity of heart failure. Galectin-3-mediated HF is inherently progressive while other forms of HF are not, increasing the proportion of galectin-3-mediated HF in patients with more advanced disease.
  4. Elevated galectin-3 is found in similar percentages of patients with systolic dysfunction (LVEF <35%), borderline (LVEF between 35% and 50%), and preserved ejection fraction (LVEF 50% or higher).

Galectin-3 shows modest correlations with clinical variables, including:

  1. Age (slightly higher levels in older subjects).
  2. Gender (women have slightly higher values).
  3. Presence of diabetes or atrial fibrillation.
  4. NYHA classification (see above).

Galectin-3 Variability

  1. Galectin-3 levels are remarkably stable over time.
  2. Galectin-3 levels do not vary with the degree of decompensation (galectin-3 testing is only indicated for patients with chronic heart failure).
  3. Galectin-3 levels should not be used to guide therapy.

Galectin-3 and Heart Failure Outcomes

  1. Galectin-3 is an independent predictor of adverse outcomes in patients with chronic heart failure.
  2. Outcomes associated with galectin-3 levels include: combined endpoint of all-cause mortality or hospitalizations and, in studies that are adequately powered, certain individual endpoints such as mortality and hospitalizations for heart failure.
  3. In studies that are adequately powered to perform such analysis, the galectin-3 effect remains significant after adjusting for variables such as age, gender, NYHA classification, LVEF, smoking, diabetes, kidney function, and natriuretic peptides.

Galectin-3 and Natriuretic Peptides

  1. Levels of galectin-3 and natriuretic peptides generally show a modest degree of concordance. Approximately 40% to 50% of the subjects are in the discordant groups.
  2. Galectin-3 and natriuretic peptides are measures of separate and distinct biological processes. Each marker provides independent and complementary information on the prognosis of patients with chronic heart failure.


Further Reading:

  1. de Boer RA, Lok D, Hillege JL, et al. Clinical and prognostic value of galectin-3, a novel fibrosis-associated biomarker. Relation with clinical and biochemical correlates of heart failure J Am Coll Cardiol. 2010;55:A26.
  2. de Boer RA, Yu L, van Veldhuisen DJ. Galectin-3 in cardiac remodeling and heart failure Curr Heart Fail Rep. 2010;7:1-8.
  3. de Boer RA, Voors AA, Muntendam P, et al. Galectin-3: a novel mediator of heart failure development and progression Eur J Heart Fail. 2009;11:811-17.
  4. deFilippi CR, Felker GM. Galectin-3 in heart failure-linking fibrosis, remodeling, and progression US Cardiology. 2010;7:67-70.
  5. deFilippi C, Christenson R, Shah R, et al. Clinical validation of a novel assay for galectin-3 for risk assessment in acutely destabilized heart failure J Card Fail. 2009;15:S9.
  6. Felker GM, Fiuzat M, Shaw LK, et al. Prognostic value of Galectin-3 in chronic heart failure: results from the HF-ACTION study. Eur Heart J. 2010;31 (Suppl 1):429.
  7. Lin YH, Lin LY, Wu YW, et al. The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients Clin Chim Acta. 2009;409:96-9.
  8. Lok D, van der Meer P, de la Porte PB, et al. Plasma galectin-3 levels predict left ventricular remodeling determined by sequential echocardiography: results from the Deventer-Alkmaar heart failure study J Am Coll Cardiol. 2010;55:A17.
  9. Lok D, van der Meer P, de la Porte PWB, et al. Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study Clin Res Cardiol. 2010;99:527.
  10. Lok D, van der Meer P, de La Porte PM, et al. Galectin-3, a novel marker of macrophage activity, predicts outcome in patients with stable chronic heart failure J Am Coll Cardiol. 2007;49:98A.
  11. Milting H, Ellinghaus P, Seewald M, et al. Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices J Heart Lung Transplant. 2008;27:589-96.
  12. Muntendam P, Adourian A, Christenson R. Reference interval for plasma galectin-3 in healthy subjects age 55 years and older Clin Chem. 2009;55:B72.
  13. Rossignol P, Fay R, Iraqi W, et al. Galectin-3 and PIIINP are associated with cardiovascular outcomes in patients with heart failure, left ventricular dysfunction and dyschrony. Insights from the CARE-HF study. Eur Heart J. 2010;31 (Suppl 1):429.
  14. Shah RV, Chen-Tournoux AA, Picard MH, et al. Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure Eur J Heart Fail. 2010;12:826-32
  15. Sherwi NS, Lukaschuk EL, Zhang J, et al. Does the severity of LV dysfunction or the extent of myocardial scar explain elevations in plasma galectin-3 in patients with heart failure Eur J Heart Fail Suppl. 2010;9:S18.
  16. van Kimmenade RR, Januzzi JL, Ellinor PT, et al. Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure J Am Coll Cardiol. 2006;48:1217-24.
  17. van Veldhuisen DJ, Lok D, Damman K, et al. Clinical and prognostic value of galectin-3, a novel fibrosis-associated biomarker, in patient with chronic heart failure J Card Fail. 2009;15:814.
  18. Zile MR, Johnson RH, DeSantis SM, et al. Plasma galectin-3 levels in patients with structural and clinical manifestations of hypertensive heart disease: relationship to determinants of matrix composition. (Presented at the American Heart Association Scientific Sessions, 2010, Chicago, IL).

For a complete list of related readings, please see our Bibliography.