Evidence map›Paper›PMID 30884964›Full record

Trial reportCirculation2019

Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients.

Roni Nielsen, Niels Møller, Lars C Gormsen, Lars Poulsen Tolbod, Nils Henrik Hansson, Jens Sorensen, Hendrik Johannes Harms, Jørgen Frøkiær, Hans Eiskjaer, Nichlas Riise Jespersen and 5 more

5 registry-linked trialsOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 294 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
294citing papers in PubMed, 5 pooled it
27.5field-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.

NCT04379934 naunknown statusnot on this mapstarted 2020, after this paper: background citation

Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure

TypeinterventionalSponsorUniversity of AarhusRan2020 to 2024Enrolled40ConditionsHeart Failure, Ischemia Reperfusion Injury, Mitochondrial PathologyArms3-hydroxybuturate
NCT04921293 naunknown statusnot on this mapstarted 2023, after this paper: background citation

Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction

TypeinterventionalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2023 to 2024Enrolled18ConditionsHeart Failure With Reduced Ejection Fraction, KetosisArmsKetogenic diet, Exogenous ketones, Standard diet + placebo
NCT05584371 naunknown statusnot on this mapstarted 2022, after this paper: background citation

Evaluation of the Safety and Tolerability of Exogenous Ketosis Induced by Free Beta-hydroxybutyrate.

TypeinterventionalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2022 to 2023Enrolled30ConditionsExogenous KetosisArmsFree Beta-hydroxybutyrate
NCT06121323 nacompletednot on this mapstarted 2023, after this paper: background citation

Physiological Effects of Lactate in Individuals With Chronic Heart Failure

TypeinterventionalSponsorHenrik WiggersRan2023 to 2025Enrolled12ConditionsHeart Failure, SystolicArmsSodium lactate infusion, Sodium lactate ingestion
NCT06398964 nacompletednot on this mapstarted 2023, after this paper: background citation

Effects of 2-week Ketosis on Myocardial Ketone Body Consumption, Utilization, and External Efficiency in Patients With Chronic Heart Failure

TypeinterventionalSponsorAarhus University HospitalRan2023 to 2025Enrolled12ConditionsHeart Failure With Reduced Ejection FractionArms3-hydroxybutyrat, Isocaloric placebo drink
3 · Its place in the literature

Who cites it

294 citing papers in PubMed, 5 syntheses or guidelines pooled it, 498 citations in OpenAlex.

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  17. ELUCIDATE Trial: A Single-Center Randomized Controlled Study.Journal of the American Heart Association · 2024
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234 more citing papers are in PubMed but not listed here.

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

15 authors at 3 institutions in 2 countries.

Roni NielsenDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Niels MøllerDepartment of Endocrinology and Metabolism (R.N., N.M.), Aarhus University Hospital, Aarhus, Denmark.
Lars C GormsenDepartment of Nuclear Medicine & PET Centre (L.C.G., L.P.T., J.S., H.J.H., J.F.), Aarhus University Hospital, Aarhus, Denmark.
Lars Poulsen TolbodDepartment of Nuclear Medicine & PET Centre (L.C.G., L.P.T., J.S., H.J.H., J.F.), Aarhus University Hospital, Aarhus, Denmark.
Nils Henrik HanssonDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Jens SorensenDepartment of Nuclear Medicine & PET Centre (L.C.G., L.P.T., J.S., H.J.H., J.F.), Aarhus University Hospital, Aarhus, Denmark.
Hendrik Johannes HarmsDepartment of Nuclear Medicine & PET Centre (L.C.G., L.P.T., J.S., H.J.H., J.F.), Aarhus University Hospital, Aarhus, Denmark.
Jørgen FrøkiærDepartment of Nuclear Medicine & PET Centre (L.C.G., L.P.T., J.S., H.J.H., J.F.), Aarhus University Hospital, Aarhus, Denmark.
Hans EiskjaerDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Nichlas Riise JespersenDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Søren MellemkjaerDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Thomas Ravn LassenDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Kasper PrydsDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Hans Erik BøtkerDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Henrik WiggersDepartment of Cardiology (R.N., N.H.H., H.E., N.R.J., S.R., T.R.L., K.P., H.E.B., H.W.), Aarhus University Hospital, Aarhus, Denmark.
Aarhus University · DKAarhus University Hospital · DKUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential dose-response relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO

methodsStudy 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37±3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a dose-response study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO

results3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4±0.3 to 3.3±0.4 mM ( P<0.001). CO rose by 2.0±0.2 L/min ( P<0.001) because of an increase in stroke volume of 20±2 mL ( P<0.001) and heart rate of 7±2 beats per minute (bpm) ( P<0.001). Left ventricular ejection fraction increased 8±1% ( P<0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM ( P<0.001). 3-OHB increased MVO

conclusions3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.

Indexed as

3-Hydroxybutyric AcidHeart FailurePositron-Emission TomographyAcetatesAgedCarbon RadioisotopesChronic DiseaseFemaleHeart RateHumansMaleMiddle AgedOxygen ConsumptionStroke Volume3-Hydroxybutyric AcidAcetatesCarbon-11Carbon Radioisotopes3-hydroxybutyrateechocardiographyheart failureketone bodiesmetabolismpositron-emission tomography

Identifiers

PMID30884964
PMCPMC6493702
OpenAlexW2925036255

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.