Evidence map›Paper›PMID 26276886›Full record

ArticleCirculation. Heart failure2015

Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure.

David J Kennedy, Kevin Shrestha, Brendan Sheehey, Xinmin S Li, Anuradha Guggilam, Yuping Wu, Michael Finucan, Alaa Gabi, Charles M Medert, Kristen Westfall and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

45 citing papers in PubMed, 54 citations in OpenAlex.

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  18. Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress.Frontiers in cell and developmental biology · 2021
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

David J KennedyFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Kevin ShresthaFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Brendan SheeheyFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Xinmin S LiFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Anuradha GuggilamFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Yuping WuFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Michael FinucanFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Alaa GabiFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Charles M MedertFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Kristen WestfallFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Allen BorowskiFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Olga FedorovaFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
Alexei Y BagrovFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.).
W H Wilson TangFrom the Department of Cellular and Molecular Medicine (D.J.K., K.S., B.S., X.S.L., A.G., Y.W., M.F., A.G., C.M.M., K.W., A.B., W.H.W.T.), Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute (W.H.W.T.), Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute (D.J.K.), and Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, Cleveland, OH; and Laboratory of Cardiovascular Science, Hypertension Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD (O.F., A.Y.B.). tangw@ccf.org.
Hypertension Institute · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Sodium pump ligands in blood pressure regulation and profibrotic signaling in hypertension, chronic kidney disease and aging in males and femalesZIAAG000609 · NIA · NATIONAL INSTITUTE ON AGING · PI FEDOROVA, OLGA V · 2009 to 2025
$17.3M
Marinobufagenin as a therapeutic targetZIAAG000869 · NIA · NATIONAL INSTITUTE ON AGING · PI LAKATTA, EDWARD · 2009 to 2025
$14.8M
Functional Cardio-MetabolomicsP20HL113452 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2012 to 2016
$4.8M
Nitrative stress in heart failureR01HL103931 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI TANG, WAI HONG WILSON · 2010 to 2014
$3.8M
Aging and interaction of natriuretic factors on renal and vascular sodium pumpZIAAG000868 · NIA · NATIONAL INSTITUTE ON AGING · PI BAGROV, ALEXEI · 2009 to 2015
$2.7M
Intramural NIH HHSNCATS NIH HHS UL1 TR000439NHLBI NIH HHS P20 HL113452NHLBI NIH HHS P20HL113452NHLBI NIH HHS R01 HL103931NHLBI NIH HHS R01HL103931
6 · The paper itself

Abstract

backgroundPlasma levels of cardiotonic steroids are elevated in volume-expanded states, such as chronic kidney disease, but the role of these natriuretic hormones in subjects with heart failure (HF) is unclear. We sought to determine the prognostic role of the cardiotonic steroids marinobufagenin (MBG) in HF, particularly in relation to long-term outcomes. METHODS AND

resultsWe first measured plasma MBG levels and performed comprehensive clinical, laboratory, and echocardiographic assessment in 245 patients with HF. All-cause mortality, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort, median (interquartile range) MBG was 583 (383-812) pM. Higher MBG was associated with higher myeloperoxidase (r=0.42, P<0.0001), B-type natriuretic peptide (r=0.25, P=0.001), and asymmetrical dimethylarginine (r=0.32, P<0.001). Elevated levels of MBG were associated with measures of worse right ventricular function (RV s', r=-0.39, P<0.0001) and predicted increased risk of adverse clinical outcomes (MBG≥574 pmol/L: hazard ratio 1.58 [1.10-2.31], P=0.014) even after adjustment for age, sex, diabetes mellitus, and ischemic pathogenesis. In mice, a left anterior descending coronary artery ligation model of HF lead to increases in MBG, whereas infusion of MBG into mice for 4 weeks lead to significant increases in myeloperoxidase, asymmetrical dimethylarginine, and cardiac fibrosis.

conclusionsIn the setting of HF, elevated plasma levels of MBG are associated with right ventricular dysfunction and predict worse long-term clinical outcomes in multivariable models adjusting for established clinical and biochemical risk factors. Infusion of MBG seems to directly contribute to increased nitrative stress and cardiac fibrosis.

Indexed as

AdultAgedAnimalsBiomarkersBufanolidesCohort StudiesDisease Models, AnimalFemaleHeart FailureHeart TransplantationHospitalizationHumansMaleMiceMice, Inbred C57BLMiddle AgedBiomarkersBufanolidesmarinobufagenincardiac fibrosiscardiotonic steroidsheart failurenitrative stressoutcome

Identifiers

PMID26276886
PMCPMC4651837
OpenAlexW2130794355

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Registered trials

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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.