Relationship between galectin-3 LEVELS and MINERALOCORTICOID RECEPTOR ANTAGONIST USE in HEART FAILURE: Analysis from HF-ACTION

Mona Fiuzat, Phillip Schulte, Michael Felker, Tariq Ahmad, Megan Neely, Kirkwood F. Adams, Mark P. Donahue, William E. Kraus, Ileana L. Piña, David J. Whellan, Christopher M. O'Connor

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION. Methods and Results HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II-IV, left ventricular ejection fraction ≤0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P =.76 for ACM+ACH; P =.26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.85-1.23, P =.8; and HR = 1.15, 95% CI [0.82-1.61], P =.4; respectively). IPW analysis was consistent with the results of the adjusted analysis. Conclusion Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.

Original languageEnglish (US)
Pages (from-to)38-44
Number of pages7
JournalJournal of Cardiac Failure
Volume20
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Fingerprint

Mineralocorticoid Receptor Antagonists
Galectin 3
Heart Failure
Mortality
Fibrosis
Confidence Intervals
Proportional Hazards Models
Stroke Volume
Patient Care
Hospitalization
Randomized Controlled Trials
Biomarkers
Exercise

Keywords

  • biomarkers
  • galectin-3
  • Heart failure
  • mineralocorticoid receptor antagonists

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relationship between galectin-3 LEVELS and MINERALOCORTICOID RECEPTOR ANTAGONIST USE in HEART FAILURE : Analysis from HF-ACTION. / Fiuzat, Mona; Schulte, Phillip; Felker, Michael; Ahmad, Tariq; Neely, Megan; Adams, Kirkwood F.; Donahue, Mark P.; Kraus, William E.; Piña, Ileana L.; Whellan, David J.; O'Connor, Christopher M.

In: Journal of Cardiac Failure, Vol. 20, No. 1, 01.2014, p. 38-44.

Research output: Contribution to journalArticle

Fiuzat, M, Schulte, P, Felker, M, Ahmad, T, Neely, M, Adams, KF, Donahue, MP, Kraus, WE, Piña, IL, Whellan, DJ & O'Connor, CM 2014, 'Relationship between galectin-3 LEVELS and MINERALOCORTICOID RECEPTOR ANTAGONIST USE in HEART FAILURE: Analysis from HF-ACTION', Journal of Cardiac Failure, vol. 20, no. 1, pp. 38-44. https://doi.org/10.1016/j.cardfail.2013.11.011
Fiuzat, Mona ; Schulte, Phillip ; Felker, Michael ; Ahmad, Tariq ; Neely, Megan ; Adams, Kirkwood F. ; Donahue, Mark P. ; Kraus, William E. ; Piña, Ileana L. ; Whellan, David J. ; O'Connor, Christopher M. / Relationship between galectin-3 LEVELS and MINERALOCORTICOID RECEPTOR ANTAGONIST USE in HEART FAILURE : Analysis from HF-ACTION. In: Journal of Cardiac Failure. 2014 ; Vol. 20, No. 1. pp. 38-44.
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abstract = "Background Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION. Methods and Results HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II-IV, left ventricular ejection fraction ≤0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P =.76 for ACM+ACH; P =.26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95{\%} confidence interval [CI] 0.85-1.23, P =.8; and HR = 1.15, 95{\%} CI [0.82-1.61], P =.4; respectively). IPW analysis was consistent with the results of the adjusted analysis. Conclusion Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.",
keywords = "biomarkers, galectin-3, Heart failure, mineralocorticoid receptor antagonists",
author = "Mona Fiuzat and Phillip Schulte and Michael Felker and Tariq Ahmad and Megan Neely and Adams, {Kirkwood F.} and Donahue, {Mark P.} and Kraus, {William E.} and Pi{\~n}a, {Ileana L.} and Whellan, {David J.} and O'Connor, {Christopher M.}",
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T1 - Relationship between galectin-3 LEVELS and MINERALOCORTICOID RECEPTOR ANTAGONIST USE in HEART FAILURE

T2 - Analysis from HF-ACTION

AU - Fiuzat, Mona

AU - Schulte, Phillip

AU - Felker, Michael

AU - Ahmad, Tariq

AU - Neely, Megan

AU - Adams, Kirkwood F.

AU - Donahue, Mark P.

AU - Kraus, William E.

AU - Piña, Ileana L.

AU - Whellan, David J.

AU - O'Connor, Christopher M.

PY - 2014/1

Y1 - 2014/1

N2 - Background Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION. Methods and Results HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II-IV, left ventricular ejection fraction ≤0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P =.76 for ACM+ACH; P =.26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.85-1.23, P =.8; and HR = 1.15, 95% CI [0.82-1.61], P =.4; respectively). IPW analysis was consistent with the results of the adjusted analysis. Conclusion Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.

AB - Background Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION. Methods and Results HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II-IV, left ventricular ejection fraction ≤0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P =.76 for ACM+ACH; P =.26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.85-1.23, P =.8; and HR = 1.15, 95% CI [0.82-1.61], P =.4; respectively). IPW analysis was consistent with the results of the adjusted analysis. Conclusion Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.

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KW - Heart failure

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