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Cardiovascular Effe...
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Nielsen, RoniAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ Hosp, Dept Endocrinol & Metab, Aarhus, Denmark
(author)
Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients
- Article/chapterEnglish2019
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LIPPINCOTT WILLIAMS & WILKINS,2019
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LIBRIS-ID:oai:DiVA.org:uu-387208
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-387208URI
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https://doi.org/10.1161/CIRCULATIONAHA.118.036459DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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BACKGROUND: Myocardial 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 doseresponse relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO 2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers.METHODS: Study 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 doseresponse 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 2 were evaluated using 11C-acetate positron emission tomography.RESULTS: 3-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 2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers.CONCLUSIONS: 3-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.
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Møller, NielsAarhus Univ Hosp, Dept Endocrinol & Metab, Aarhus, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Gormsen, Lars C.Aarhus Univ Hosp, Dept Nucl Med, Aarhus, Denmark;Aarhus Univ Hosp, PET Ctr, Aarhus, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Tolbod, Lars PoulsenAarhus Univ Hosp, Dept Nucl Med, Aarhus, Denmark;Aarhus Univ Hosp, PET Ctr, Aarhus, Denmark
(author)
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Hansson, Nils HenrikAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
(author)
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Sörensen, JensUppsala universitet,Radiologi,Aarhus Univ Hosp, Dept Nucl Med, Aarhus, Denmark;Aarhus Univ Hosp, PET Ctr, Aarhus, Denmark(Swepub:uu)jenssore
(author)
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Harms, Hendrik JohannesAarhus Univ Hosp, Dept Nucl Med, Aarhus, Denmark;Aarhus Univ Hosp, PET Ctr, Aarhus, Denmark
(author)
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Frøkiaer, JørgenAarhus Univ Hosp, Dept Nucl Med, Aarhus, Denmark;Aarhus Univ Hosp, PET Ctr, Aarhus, Denmark
(author)
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Eiskjaer, HansAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
(author)
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Jespersen, Nichlas RiiseAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Mellemkjaer, SorenAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
(author)
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Lassen, Thomas RavnAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Pryds, KasperAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Bøtker, Hans ErikAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Wiggers, HenrikAarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(author)
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Aarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark;Aarhus Univ Hosp, Dept Endocrinol & Metab, Aarhus, DenmarkAarhus Univ Hosp, Dept Endocrinol & Metab, Aarhus, Denmark;Aarhus Univ, Dept Clin Med, Fac Hlth, Aarhus, Denmark
(creator_code:org_t)
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In:Circulation: LIPPINCOTT WILLIAMS & WILKINS139:18, s. 2129-21410009-73221524-4539
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Nielsen, Roni
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Møller, Niels
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Gormsen, Lars C.
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Tolbod, Lars Pou ...
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Sörensen, Jens
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Harms, Hendrik J ...
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Frøkiaer, Jørgen
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Eiskjaer, Hans
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Lassen, Thomas R ...
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Pryds, Kasper
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Wiggers, Henrik
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