Galectin-3 in heart failure with preservedejection fraction. A RELAX trial substudy (phosphodiesterase-5 inhibition to improve clinical status and exercise capacity in diastolic heartfailure).

Omar F. AbouEzzeddine, Phillip Haines, Susanna Stevens, Jose Nativi-Nicolau, G. Michael Felker, Barry A. Borlaug, Horng H. Chen, Russell P. Tracy, Eugene Braunwald, Margaret M. Redfield

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalJACC: Heart Failure
Volume3
Issue number3
DOIs
StatePublished - Mar 1 2015

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Keywords

  • Biomarkers
  • Diastole
  • Galectin-3
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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