Evidence map›Paper›PMID 25742762›Full record

Trial reportJACC. Heart failure2015

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).

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

Open access · greenAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JACC. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
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  12. The immunology of heart failure with preserved ejection fraction.Clinical science (London, England : 1979) · 2023
    Review
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  16. The prognostic value of diastolic and systolic mechanical left ventricular dyssynchrony among patients with coronary artery disease and heart failure.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2020
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  18. Observational
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 1 country.

Omar F AbouEzzeddineDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Phillip HainesDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Susanna StevensDepartment of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, North Carolina.
Jose Nativi-NicolauDepartment of Medicine, University of Utah Health Care, Salt Lake City, Utah.
G Michael FelkerDepartment of Medicine, Duke University Medical Center, Durham, North Carolina.
Barry A BorlaugDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Horng H ChenDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Russell P TracyDepartment of Pathology and Biochemistry, University of Vermont, Burlington, Vermont.
Eugene BraunwaldDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Margaret M RedfieldDepartment of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: redfield.margaret@mayo.edu.
Mayo Clinic · USBrigham and Women's Hospital · USClinical Research Institute · USDuke Medical Center · USUniversity of Pennsylvania · USUniversity of Utah Health Care · USUniversity of Vermont · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
STEERING COMMITTEEU54MD008149 · NIMHD · MOREHOUSE SCHOOL OF MEDICINE · PI OFILI, ELIZABETH O. · 2012 to 2018
$21.1M
Heart Failure Clinical Research Network - DCCU01HL084904 · NHLBI · DUKE UNIVERSITY · PI LEE, KERRY L · 2006 to 2011
$19.8M
Mayo Heart Failure Regional Clinical CenterU10HL110262 · NHLBI · MAYO CLINIC ROCHESTER · PI REDFIELD, MARGARET M · 2012 to 2018
$3.6M
Heart Failure Clinical Research Network Regional Clinical Center (U10)U10HL110312 · NHLBI · DUKE UNIVERSITY · PI FELKER, GARY M · 2012 to 2018
$3.5M
Partners Heart Failure NetworkU01HL084877 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI STEVENSON, LYNNE W · 2006 to 2011
$2.9M
Heart Failure Clinical Research Network - RCCU01HL084875 · NHLBI · DUKE UNIVERSITY · PI O'CONNOR, CHRISTOPHER M · 2006 to 2011
$2.6M
Heart Failure Clinical Trials NetworkU10HL110302 · NHLBI · EMORY UNIVERSITY · PI SMITH, ANDREW · 2012 to 2018
$2.5M
Mayo Heart Failure Regional Clinical CenterU01HL084907 · NHLBI · MAYO CLINIC ROCHESTER · PI REDFIELD, MARGARET M · 2006 to 2011
$2.4M
The Texas Medical Center Regional Coordinating Center for Heart FailureU01HL084890 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI DESWAL, ANITA · 2006 to 2011
$1.8M
Gene- and Cell-based therapies for LVAD patientsU01HL084889 · NHLBI · UNIVERSITY OF UTAH · PI BULL, DAVID ANDREW · 2006 to 2011
$1.8M
New England, New York and Quebec Regional Clinical CenterU01HL084899 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI LEWINTER, MARTIN M · 2006 to 2011
$1.6M
NCATS NIH HHS UL1 TR000135NHLBI NIH HHS R01 HL105418NHLBI NIH HHS U01 HL084861NHLBI NIH HHS U01HL084861NHLBI NIH HHS U01 HL084875NHLBI NIH HHS U01HL084875NHLBI NIH HHS U01 HL084877NHLBI NIH HHS U01HL084877NHLBI NIH HHS U01 HL084889NHLBI NIH HHS U01HL084889NHLBI NIH HHS U01 HL084890NHLBI NIH HHS U01HL084890NHLBI NIH HHS U01 HL084891NHLBI NIH HHS U01HL084891NHLBI NIH HHS U01 HL084899NHLBI NIH HHS U01HL084899NHLBI NIH HHS U01 HL084904NHLBI NIH HHS U01HL084904NHLBI NIH HHS U01 HL084907NHLBI NIH HHS U01HL084907NHLBI NIH HHS U01 HL084931NHLBI NIH HHS U01HL084931NHLBI NIH HHS U10 HL110262NHLBI NIH HHS U10 HL110302NHLBI NIH HHS U10 HL110312NIMHD NIH HHS U54 MD008149
6 · The paper itself

Abstract

objectivesThis 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.

backgroundGal-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.

methodsTwo 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.

resultsGal-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).

conclusionsIn 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.

Indexed as

AgedEnzyme-Linked Immunosorbent AssayExercise ToleranceFemaleGalectin 3Heart Failure, DiastolicHumansMaleMiddle AgedPhosphodiesterase 5 InhibitorsQuality of LifeStroke VolumeVentricular Function, LeftGalectin 3Phosphodiesterase 5 Inhibitorsbiomarkersdiastolegalectin-3heart failure

Identifiers

PMID25742762
PMCPMC4369675
OpenAlexW1506577935

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.