Diagnosis, Definition, and Risk Stratification
Prognosis for Heart Failure: New Biomarkers
While BNP and NT-proBNP can be used for prognostic purposes, new biomarkers are available that can assist in the prognosis for patients already diagnosed with heart failure, and can aid in risk stratification, earlier detection of treatment failure, and therapeutic targets.
Galectin-3 is a biomarker which appears to be actively involved in both the inflammatory and fibrotic pathways that are thought to be involved. It 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.
Clinically, galectin-3 concentrations may be categorized into 3 risk categories which are substantiated by results from several large chronic heart failure studies:1–3
Risk Categories of Galectin-3 Concentrations
|Low risk||< or =17.8 ng/mL|
|Intermediate risk||17.9-25.9 ng/mL|
|Higher risk||>25.9 ng/mL|
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.
Soluble ST2 is a biomarker that appears to be actively involved with interleukin-33 (IL-33) in modulating cardiac remodeling and ventricular function via effects in the inflammatory and apoptosis pathways.4
ST2 is a member of the interleukin-1 receptor family and has 2 isoforms that are directly implicated in progression of cardiac disease: soluble ST2 (sST2) and a transmembrane-bound form, ST2 ligand (ST2L). IL-33 is the hormone that interacts with ST2L, protecting against left ventricular hypertrophy and myocardial fibrosis to effectively preserve cardiac function. Therefore, when sST2 concentrations are high, IL-33 is unavailable for cardioprotective signaling, leaving the heart vulnerable to the effects of sST2. High concentrations of sST2 result in cellular death, tissue fibrosis, reduced cardiac function, and an increase in the rate of disease progression.
Clinically, ST2 concentrations in the HF-ACTION heart failure study were a significant predictor of mortality, all-cause hospitalization, mortality due to cardiovascular disease, and hospitalization due to cardiovascular disease when using a cutpoint of 35 ng/mL. In addition, mortality risk was significantly higher in patients with ST2 >35 ng/mL.5 The risk appears early and persists throughout the follow-up period.
- 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)
- 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
- 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
- Seki K, Sanada S, Kudinova AY, et al: Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail 2009;2(6):684-691
- Whellan DJ, O’Connor CM, Lee, KL, et al: HF-ACTION Trial Investigators. Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale. Am Heart J 2007;153(2):201-221