ArticleCirculation2016
The Failing Heart Relies on Ketone Bodies as a Fuel.
Erratum issued Registry-linked trialOpen access · bronzeAbstract read
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. An erratum has been issued. It is linked to trial NCT04921293 (Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction), which is not on this map. Cited by 434 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
434citing papers in PubMed, 1 pooled it
38.4field-weighted citation impact, top 1% of its field
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.
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.
Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction
Who cites it
434 citing papers in PubMed, 1 synthesis or guideline pooled it, 688 citations in OpenAlex.
- Update on the Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Chronic Diseases: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Retatrutide and lipid and metabolite profiles in participants with obesity with or without type 2 diabetes.The Journal of clinical endocrinology and metabolism · 2026Trial
- Cardiopulmonary responses to acute exogenous ketosis at rest, and during submaximal and maximal exercise.Physiological reports · 2025Trial
- A ketogenic-promoting beverage acutely elevates cardiac function and myocardial blood flow compared to placebo in adults: A cardiac MRI investigation.Physiological reports · 2025Trial
- Cardiovascular and Metabolic Effects of Modulating Circulating Ketone Bodies With 1,3-Butanediol in Patients With Heart Failure With Reduced Ejection Fraction.Journal of the American Heart Association · 2025Trial
- Fasting substrates predict chronic kidney disease progression in CREDENCE trial patients with type 2 diabetes.JCI insight · 2024 · on this mapTrial
- Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.Circulation · 2024Trial
- Acute effects of β-hydroxybutyrate on left ventricular function in young, healthy adults.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Trial
- Stimulation of the Hydroxycarboxylic Acid Receptor 2 With the Ketone Body 3-Hydroxybutyrate and Niacin in Patients With Chronic Heart Failure: Hemodynamic and Metabolic Effects.Journal of the American Heart Association · 2023Trial
- Sustained alternate-day fasting potentiates doxorubicin cardiotoxicity.Cell metabolism · 2023Trial
- Trial
- Plasma acylcarnitines and risk of incident heart failure and atrial fibrillation: the Prevención con dieta mediterránea study.Revista espanola de cardiologia (English ed.) · 2022Trial
- Cardiovascular imaging with total-body PET.The British journal of radiology · 2026Review
- Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Metabolic Task Analysis Reveals Distinct Metabotypes in End-Stage Dilated Cardiomyopathy.Circulation. Genomic and precision medicine · 2026Article
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Association Between Endogenous Ketosis and Risk of Atrial Fibrillation in Intensive Care Versus General Ward Patients: A Retrospective Cohort Study.Journal of clinical medicine · 2026Article
- Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive Substrate?International journal of molecular sciences · 2026Review
- Ketone Body Metabolism and Sodium Glucose Cotransporter 2 Inhibitor Response in Heart Failure With Ischemic Cause: A Precision Medicine Approach Using Metabolomics Integration With Global Burden of Disease Population Data Across Diverse Genetic Backgrounds.Journal of the American Heart Association · 2026Article
374 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Gregory AubertFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Ola J MartinFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Julie L HortonFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Ling LaiFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Rick B VegaFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Teresa C LeoneFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Timothy KovesFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Stephen J GardellFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Marcus KrügerFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Charles L HoppelFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
E Douglas LewandowskiFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Peter A CrawfordFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Deborah M MuoioFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
Daniel P KellyFrom Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.). dkelly@sbpdiscovery.org.
University of Cologne · DECologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · DECase Western Reserve University · USUniversity of Illinois Chicago · US
Funding
REGULATION OF FATTY ACID OXIDATION DURING CARDIAC GROWTHR01HL058493 · NHLBI · WASHINGTON UNIVERSITY · PI KELLY, DANIEL PATRICK · 1998 to 2024
$10.6MKETONE BODY METABOLISM AND INTEGRATED METABOLIC HOMEOSTASISR01DK091538 · NIDDK · WASHINGTON UNIVERSITY · PI CRAWFORD, PETER A · 2011 to 2024
$6.2MProbing the Role of Mitochondrial Short-chain Carbon Homeostasis in the Hypertrophied and Failing HeartR01HL128349 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUOIO, DEBORAH M · 2016 to 2024
$6.1MNMR OF MITOCHONDRIAL TRANSPORTERS IN CARDIAC HYPERTROPHYR01HL062702 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LEWANDOWSKI, E DOUGLAS · 1999 to 2013
$4.4MMagnetic Resonance of Cardiac C13 Flux & Metabolism RateR01HL049244 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LEWANDOWSKI, E DOUGLAS · 1993 to 2018
$3.7MA Genomic/Metabolomic Strategy to Characterize Cardiac Mitochondrial DysfunctionR01HL101189 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI KELLY, DANIEL PATRICK, MUOIO, DEBORAH M · 2010 to 2013
$2.9MNHLBI NIH HHS R01 HL049244NHLBI NIH HHS R01 HL058493NHLBI NIH HHS R01 HL062702NHLBI NIH HHS R01 HL101189NHLBI NIH HHS R01 HL128349NHLBI NIH HHS R01 HL49244NIDDK NIH HHS R01 DK091538
Abstract
backgroundSignificant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardial fuel oxidation could unveil novel strategies to treat heart failure. METHODS AND
resultsQuantitative mitochondrial proteomics was used to identify energy metabolic derangements that occur during the development of cardiac hypertrophy and heart failure in well-defined mouse models. As expected, the amounts of proteins involved in fatty acid utilization were downregulated in myocardial samples from the failing heart. Conversely, expression of β-hydroxybutyrate dehydrogenase 1, a key enzyme in the ketone oxidation pathway, was increased in the heart failure samples. Studies of relative oxidation in an isolated heart preparation using ex vivo nuclear magnetic resonance combined with targeted quantitative myocardial metabolomic profiling using mass spectrometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fuel source in the context of reduced capacity to oxidize fatty acids. Distinct myocardial metabolomic signatures of ketone oxidation were identified.
conclusionsThese results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant fuel source for oxidative ATP production. Specific metabolite biosignatures of in vivo cardiac ketone utilization were identified. Future studies aimed at determining whether this fuel shift is adaptive or maladaptive could unveil new therapeutic strategies for heart failure.
Indexed as
AnimalsDiet, KetogenicFatty AcidsFemaleGene Expression ProfilingHeart FailureKetone BodiesMiceMice, Inbred C57BLFatty AcidsKetone Bodiesfatty acidsheart failurehypertrophymetabolismmolecular biology
Identifiers
What OpenQuestion holds
Textmetadata
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Read underepoch 390
Registered trials
NCT04921293ClinicalTrials.gov
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.