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).
OBJECTIVE
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.
Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Omar F
OF
AbouEzzeddine
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Phillip
P
Haines
Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, North Carolina.
Susanna
S
Stevens
Department of Medicine, University of Utah Health Care, Salt Lake City, Utah.
Jose
J
Nativi-Nicolau
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
G Michael
GM
Felker
Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Barry A
BA
Borlaug
Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Horng H
HH
Chen
Department of Pathology and Biochemistry, University of Vermont, Burlington, Vermont.
Russell P
RP
Tracy
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Eugene
E
Braunwald
Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: redfield.margaret@mayo.edu.
Margaret M
MM
Redfield
D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology*; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D054144:Heart Failure, Diastolic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011788:Quality of Life; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D037502:Galectin 3; D058986:Phosphodiesterase 5 Inhibitors
biomarkers; diastole; galectin-3; heart failure