Galectin-3 Studies

Since the development of BGM Galectin-3™, levels of galectin-3 have been measured in more than 15,000 samples from participants in a variety of heart failure related studies. The majority of these studies were conducted in 2009 and 2010, and the results are finding their way into the peer-reviewed medical literature and presentations at medical meetings. Two studies (HF-ACTION and COACH), described below, were conducted in support of the current intended use of BGM Galectin-3 as an aid in assessing the prognosis of patients diagnosed with chronic heart failure.

Galectin-3 Sub-Study
 Study Title
 N (approx.) Publication

Major Clinical Studies on the Effect of Galectin-3 in Chronic Heart Failure
HF-ACTION “Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training—Galectin-3 Sub-Study” 895  
COACH “Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure—Galectin-3 Sub-Study” 592  

Other Clinical Studies on the Effect of Galectin-3 in Heart Failure
CARE-HF “Cardiac Resynchronisation in Heart Failure—Galectin-3 Sub-Study” 260  
DEAL-HF “Deventer-Alkmaar Heart Failure Study—Galectin-3 Sub-Study” 232

PRIDE “The N-Terminal Pro-BNP Investigation of Dyspnea in the Emergency Department Study—Galectin-3 Sub-Study” 181  

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HF-ACTION

The HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing) study is a multicenter, randomized controlled trial sponsored by the National Heart Lung and Blood Institute. A prospective sub-study was designed and conducted in collaboration with Duke Clinical Research Institute to evaluate and validate galectin-3 using a priori defined cut-off levels of 17.8 ng/mL and 25.9 ng/mL.

HF-ACTION enrolled a total of 2,331 subjects across 82 sites (67 in the US, 9 in Canada, and 6 in France). Patients with a left ventricular ejection fraction of 35% or less and New York Heart Association (NYHA) class II, III, or IV symptoms were enrolled. Median follow-up was approximately 30 months for all participants. Enrolled patients were randomized to either usual care or usual care plus exercise therapy. The study failed to demonstrate a statistically significant effect of exercise training on the primary endpoint of the composite of all-cause mortality and all-cause hospitalization.

For the galectin-3 HF-ACTION sub-study, galectin-3 levels were measured in 895 banked EDTA-plasma samples. The average age of patients was 58 years; 71% were male, 64% were Caucasian, and a majority were in NYHA class II and III. The median follow-up time was approximately 30 months. Cox regression models were used to evaluate the association of baseline galectin-3 levels in HF patients with the endpoints of: (i) composite of all-cause mortality and all-cause hospitalization (Figure 3, Table 1, and Table 2); (ii) cardiovascular mortality (Figure 4, Table 3, and Table 4); (iii) composite of cardiovascular mortality and heart failure related hospitalization (Figure 5, Table 5, and Table 6); and (iv) all-cause mortality (Table 7 and Table 8). Galectin-3 levels were found to be associated with increased risk at each of these endpoints; these results were statistically significant. Further, the association between galectin-3 levels and increased risk remained statistically significant upon adjustment for baseline risk factors of age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status. Figure 6 displays Kaplan-Meier curves for the composite endpoint of all-cause mortality or all-cause hospitalization, by baseline galectin-3 category.

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Figure 1: HF-ACTION Galectin-3 Sub-Study Design
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Figure 2: HF-ACTION Galectin-3 Sub-Study NYHA Class Distribution (N=895)
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Figure 3: HF-ACTION Galectin-3 Sub-Study Cumulative Probability of Event for the Composite Endpoint
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Figure 4: HF-ACTION Galectin-3 Sub-Study Cumulative Probability of Event for the Endpoint of Cardiovascular Mortality
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Figure 5: HF-ACTION Galectin-3 Sub-Study Cumulative Probability of Event for the Composite Endpoint of Cardiovascular Mortality and Heart Failure-Related Hospitalization
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Figure 6: HF-ACTION Galectin-3 Sub-Study Cumulative Probability of Event for the Composite Endpoint of All-Cause Mortality and All-Cause Hospitalization
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Further Reading:

  1. O’Connor CM; Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial JAMA. 2009;301:1439-50.
  2. 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.

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COACH

The COACH (Coordinating Study on Outcomes of Advising and Counseling in Heart Failure) study is a multicenter, randomized, controlled trial conducted in The Netherlands. A prospective sub-study was designed and conducted in collaboration with the University Medical Center Groningen, The Netherlands, to evaluate galectin-3 in patients with chronic heart failure and to define cut-off levels for subsequent validation studies.

COACH enrolled a total of 1023 subjects following hospitalization for heart failure. Patients with a left ventricular ejection fraction of 35% or less and New York Heart Association (NYHA) class II, III, or IV symptoms were enrolled. Median follow-up was approximately 30 months for all participants. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary endpoints were time to death or re-hospitalization because of HF, and the number of days lost to death or hospitalization. The study failed to demonstrate a statistically significant effect of intensive disease management on the combined endpoints of death and hospitalization due to HF when compared to usual care.

For the COACH galectin-3 sub-study, galectin-3 levels were measured in 582 banked EDTA-plasma samples. The mean age of the participants was 72±12 years; 65% were male, 50% were in NYHA class II and 50% were in NYHA class III-IV. Mean LVEF was 33±15%, mean BNP was 448 pg/mL. Average follow-up was for 18 months. The primary endpoint was a composite of all-cause mortality and HF hospitalization. During follow-up, 248 patients reached the primary endpoint (164 died). Galectin-3 remained an independent predictor of mortality and HF hospitalization even after adjusting for age, gender, renal function, and natriuretic peptides. Based on a tertile analysis the following two cut-off values were determined: 17.8 and 25.9 ng/mL.

Figure 9 and Figure 10 show the cumulative probability of event for the endpoint of all-cause mortality by two and three galectin-3 categories, respectively. Figure 11 and Figure 12 show the cumulative probability of event for the composite endpoint of cardiovascular mortality and heart failure related hospitalization by two and three galectin-3 categories, respectively. Figure 13 and Figure 14 show all-cause mortality and composite of primary endpoint at one year by galectin-3 values, respectively. Figure 15 shows the cumulative probability of event at one year by galectin-3 and BNP values.

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Figure 7: COACH Galectin-3 Sub-Study Design

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Figure 8: COACH Galectin-3 Sub-Study NYHA Classification Distribution (N=582)

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Figure 9: COACH Galectin-3 Sub-Study Cumulative Probability of Event for the Endpoint of All-Cause Mortality (2 Categories)

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Figure 10: COACH Galectin-3 Sub-Study Cumulative Probability of Event for the Endpoint of All-Cause Mortality (3 Categories)

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Figure 11: COACH Galectin-3 Sub-Study Cumulative Probability of Event for the Composite Endpoint of Cardiovascular Mortality and Heart Failure-Related Hospitalization (2 Categories)

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Figure 12: COACH Galectin-3 Sub-Study Cumulative Probability of Event for the Composite Endpoint of Cardiovascular Mortality and Heart Failure-Related Hospitalization (3 Categories)

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Figure 13: COACH Galectin-3 Sub-Study All-Cause Mortality at 1-year by Galectin-3 Values

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Figure 14: COACH Galectin-3 Sub-Study Composite Endpoint of Cardiovascular Mortality or Heart Failure-Related Hospitalization at 1-year by Galectin-3 Values

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.Figure 15: COACH Galectin-3 Sub-Study-All-Cause Mortality by Galectin-3 and BNP Values at 1-year

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Further Reading:

  1. Jaarsma T, van der Wal MH, Hogenhuis J, et al. Design and methodology of the COACH study: a multicenter randomized coordinating study evaluating outcomes of advising and counseling in heart failure Eur J  of Heart Fail. 2004;6:227-33.
  2. Jaarsma T, van der Wal MH, Leesman-Leegte I, et al. Effect of moderate or intensive disease management program on outcome in patients with heart failure Arch Intern Med. 2008;168:316-24.

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