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JACC Heart Fail. 2015 Mar;3(3):245-52. doi: 10.1016/j.jchf.2014.10.009.

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

Author information

1
Department of Medicine, Mayo Clinic, Rochester, Minnesota.
2
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
3
Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, North Carolina.
4
Department of Medicine, University of Utah Health Care, Salt Lake City, Utah.
5
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
6
Department of Pathology and Biochemistry, University of Vermont, Burlington, Vermont.
7
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
8
Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: redfield.margaret@mayo.edu.

Abstract

OBJECTIVES:

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains.

BACKGROUND:

Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF.

METHODS:

Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested.

RESULTS:

Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53).

CONCLUSIONS:

In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF.

KEYWORDS:

biomarkers; diastole; galectin-3; heart failure

PMID:
25742762
PMCID:
PMC4369675
DOI:
10.1016/j.jchf.2014.10.009
[Indexed for MEDLINE]
Free PMC Article

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