Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: A Randomized, Controlled, Double-Blind Trial.
3-hydroxybutyrate
cardiac output
cardiogenic shock
invasive hemodynamics
ketone ester
metabolism
Journal
JACC. Heart failure
ISSN: 2213-1787
Titre abrégé: JACC Heart Fail
Pays: United States
ID NLM: 101598241
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
20
02
2023
revised:
16
05
2023
accepted:
26
05
2023
medline:
6
10
2023
pubmed:
15
7
2023
entrez:
15
7
2023
Statut:
ppublish
Résumé
Cardiogenic shock (CS) is a life-threatening condition with sparse treatment options. The ketone body 3-hydroxybutyrate has favorable hemodynamic effects in patients with stable chronic heart failure. Yet, the hemodynamic effects of exogenous ketone ester (KE) in patients with CS remain unknown. The authors aimed to assess the hemodynamic effects of single-dose enteral treatment with KE in patients with CS. In a double-blind, crossover study, 12 patients with CS were randomized to an enteral bolus of KE and isocaloric, isovolumic placebo containing maltodextrin. Patients were assessed with pulmonary artery catheterization, arterial blood samples, echocardiography, and near-infrared spectroscopy for 3 hours following each intervention separated by a 3-hour washout period. KE increased circulating 3-hydroxybutyrate (2.9 ± 0.3 mmol/L vs 0.2 ± 0.3 mmol/L, P < 0.001) and was associated with augmented cardiac output (area under the curve of relative change: 61 ± 22 L vs 1 ± 18 L, P = 0.044). Also, KE increased cardiac power output (0.07 W [95% CI: 0.01-0.14]; P = 0.037), mixed venous saturation (3 percentage points [95% CI: 1-5 percentage points]; P = 0.010), and forearm perfusion (3 percentage points [95% CI: 0-6 percentage points]; P = 0.026). Right (P = 0.048) and left (P = 0.017) ventricular filling pressures were reduced whereas heart rate and mean arterial and pulmonary arterial pressures remained similar. Left ventricular ejection fraction improved by 4 percentage points (95% CI: 2-6 percentage points; P = 0.005). Glucose levels decreased by 2.6 mmol/L (95% CI: -5.2 to 0.0; P = 0.047) whereas insulin levels remained unaltered. Treatment with KE improved cardiac output, biventricular function, tissue oxygenation, and glycemic control in patients with CS (Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock [KETO-SHOCK1]; NCT04642768).
Sections du résumé
BACKGROUND
Cardiogenic shock (CS) is a life-threatening condition with sparse treatment options. The ketone body 3-hydroxybutyrate has favorable hemodynamic effects in patients with stable chronic heart failure. Yet, the hemodynamic effects of exogenous ketone ester (KE) in patients with CS remain unknown.
OBJECTIVES
The authors aimed to assess the hemodynamic effects of single-dose enteral treatment with KE in patients with CS.
METHODS
In a double-blind, crossover study, 12 patients with CS were randomized to an enteral bolus of KE and isocaloric, isovolumic placebo containing maltodextrin. Patients were assessed with pulmonary artery catheterization, arterial blood samples, echocardiography, and near-infrared spectroscopy for 3 hours following each intervention separated by a 3-hour washout period.
RESULTS
KE increased circulating 3-hydroxybutyrate (2.9 ± 0.3 mmol/L vs 0.2 ± 0.3 mmol/L, P < 0.001) and was associated with augmented cardiac output (area under the curve of relative change: 61 ± 22 L vs 1 ± 18 L, P = 0.044). Also, KE increased cardiac power output (0.07 W [95% CI: 0.01-0.14]; P = 0.037), mixed venous saturation (3 percentage points [95% CI: 1-5 percentage points]; P = 0.010), and forearm perfusion (3 percentage points [95% CI: 0-6 percentage points]; P = 0.026). Right (P = 0.048) and left (P = 0.017) ventricular filling pressures were reduced whereas heart rate and mean arterial and pulmonary arterial pressures remained similar. Left ventricular ejection fraction improved by 4 percentage points (95% CI: 2-6 percentage points; P = 0.005). Glucose levels decreased by 2.6 mmol/L (95% CI: -5.2 to 0.0; P = 0.047) whereas insulin levels remained unaltered.
CONCLUSIONS
Treatment with KE improved cardiac output, biventricular function, tissue oxygenation, and glycemic control in patients with CS (Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock [KETO-SHOCK1]; NCT04642768).
Identifiants
pubmed: 37452805
pii: S2213-1779(23)00306-2
doi: 10.1016/j.jchf.2023.05.029
pii:
doi:
Substances chimiques
Ketones
0
3-Hydroxybutyric Acid
TZP1275679
Ketone Bodies
0
Banques de données
ClinicalTrials.gov
['NCT04642768']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1337-1347Informations de copyright
Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures This study was supported by the Independent Research Fund Denmark (0134-00043B), The Danish Heart Foundation (19-R135-A9280-22126), the Novo Nordisk Foundation (NNF17OC0028230), the Arvid Nilsson Foundation, and Ellen og Ivan Osiiers Legat. Dr Wiggers has been the principal or a subinvestigator in studies involving MSD, Bayer, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi-Aventis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.