Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Heart failure is a complex cardiovascular disorder with a variety of etiologies and heterogeneity with respect to the clinical presentation of the patient. Heart failure is significantly increasing in prevalence with an aging population and is associated with high short- and long-term mortality rate. Over 80% of patients diagnosed and treated for acute heart failure syndromes in the emergency department are readmitted within the forthcoming year, incurring costly treatments and therapies.(1)
The development and progression of heart failure is a clinically-silent process until manifestation of the disorder, which typically occurs late and irreversibly into its progression. Mechanistically, heart failure, whether due to systolic or diastolic dysfunction, is thought to progress primarily through adverse cardiac remodeling and fibrosis in response to cardiac injury and/or stress. Galectin-3 is a biomarker which appears to be actively involved in both the inflammatory and fibrotic pathways that are thought to be involved.
Galectin-3 is a carbohydrate-binding lectin whose expression is associated with inflammatory cells including macrophages, neutrophils, and mast cells. Galectin-3 has been linked to cardiovascular physiological processes including myofibroblast proliferation, tissue repair, and cardiac remodeling in the setting of heart failure. Concentrations of galectin-3 have been used to predict adverse remodeling after a variety of cardiac insults.
An aid in prognosis for patients diagnosed with heart failure
Risk-stratification of heart failure patients
An early indication of treatment failure and as a therapeutic target
Clinically, galectin-3 concentrations may be categorized into 3 risk categories, substantiated by results from several large chronic heart failure studies: (2-4)
< or =17.8 ng/mL (low risk)
17.9-25.9 ng/mL (intermediate risk)
>25.9 ng/mL (higher risk)
Results should be interpreted in the context of the individual patient presentation. Elevated galectin-3 results indicate an increased risk for adverse outcomes and signal the presence of galectin-3-mediated fibrosis and adverse remodeling. Once galectin-3 concentrations are elevated they are relatively stable over time in the absence of intervention.
Knowledge of a heart failure patient’s galectin-3 results may assist in risk stratification and lead to more aggressive management. There are no specific galectin-3 inhibitors available at this time and heart failure patients with elevated galectin-3 concentrations should be treated and monitored according to established guidelines. Angiotensin receptor blockers (ARBs) and aldosterone antagonists are thought to be particularly effective.
A large multicenter, prospective, observational study was conducted to derive the reference intervals for galectin-3 which included 1,092 subjects between the ages of 55 and 80 years without any known cardiac disease (520 males, 572 females).(5) The 97.5th percentile of galectin-3 in that cohort was 22.1 ng/mL. Individuals with concentrations >22.1 ng/mL had a significant association with mortality and New York Heart Association (NYHA) classification. However, this was an older population and definitive evidence of cardiac disease was not documented.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Galectin-3 has not been shown to be useful in the acute diagnosis of heart failure, and natriuretic peptides (BNP or NT-proBNP) should be utilized for this purpose.
Hemolysis has been shown to interfere with the galectin-3 assay due to intracellular release of galectin-3. Specimens which are visibly hemolyzed will be rejected.
Heterophile antibodies, in particular human antimouse antibodies in human serum, may cause falsely elevated galectin-3 results. Heterophile antibodies may react with reagent immunoglobulins and subsequently interfere with in vitro immunoassays. Patients routinely exposed to animals or to animal serum products can be prone to this interference and anomalous high or low values can be observed.
Patients with high concentrations of rheumatoid factor as well as other autoimmune disorders may also yield falsely elevated results and should be interpreted with caution.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< 18 years: Not established
> or =18 years: < or =22.1 ng/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Weintraub NL, Collins SP, Pang PS, et al: Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association. Circulation 2010;122:1975-1996
2. Felker GM, Fiuzat M, Shaw LK, et al: Galectin-3 in Ambulatory Patients With Heart Failure: Results from the HF-ACTION Study. Circulation 2012 (in press)
3. Lok DJ, Van Der Meer P, de la Porte PW, 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 May;99(5):323-328
4. de Boer RA, Lok DJ, Jaarsma T, et al: Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction. Ann Med 2011 Feb;43(1):60-68
5. Christenson RH, Duh SH, Wu AH, et al: Multi-center determination of galectin-3 assay performance characteristics: Anatomy of a novel assay for use in heart failure. Clin Biochem 2010 May;43(7-8):683-690