Evidence map›Paper›PMID 26819374›Full record

ArticleCirculation2016

Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure.

Kenneth C Bedi, Nathaniel W Snyder, Jeffrey Brandimarto, Moez Aziz, Clementina Mesaros, Andrew J Worth, Linda L Wang, Ali Javaheri, Ian A Blair, Kenneth B Margulies and 1 more

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

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 406 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
406citing papers in PubMed, 1 pooled it
32.1field-weighted citation impact, top 1% 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

406 citing papers in PubMed, 1 synthesis or guideline pooled it, 643 citations in OpenAlex.

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  7. Acute effects of β-hydroxybutyrate on left ventricular function in young, healthy adults.Journal of applied physiology (Bethesda, Md. : 1985) · 2023
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346 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Kenneth C BediFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Nathaniel W SnyderFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Jeffrey BrandimartoFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Moez AzizFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Clementina MesarosFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Andrew J WorthFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Linda L WangFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Ali JavaheriFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Ian A BlairFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
Kenneth B MarguliesFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.).
J Eduardo RameFrom Cardiovascular Institute University of Pennsylvania Perelman School of Medicine, Smilow Translational Research Center, Philadelphia, PA (K.C.B., J.B., A.J., K.B.M., J.E.R.); A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA (N.W.S.); and Center of Cancer Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.A., C.M., A.J.W., L.L.W., I.A.B.). Eduardo.rame@uphs.upenn.edu.
Drexel University · US

Funding

Integrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9M
Endogenous Cardiac Repair in HumansR01HL089847 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MARGULIES, KENNETH BER · 2009 to 2012
$1.9M
NHLBI NIH HHS R01 HL089847NHLBI NIH HHS R01 HL105993
6 · The paper itself

Abstract

backgroundThe failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se. METHODS AND

resultsWe performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl-CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of β-hydroxybutyrate and acetoacetate.

conclusionsThese findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart.

Indexed as

Disease ProgressionAdultAgedCase-Control StudiesChronic DiseaseFemaleHeart FailureHumansKetonesLipid MetabolismMaleMiddle AgedMyocardiumKetonescardiomyopathiesheart failureketoneslipidsmetabolism

Identifiers

PMID26819374
PMCPMC4779339
OpenAlexW2274126817

What OpenQuestion holds

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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.