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Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: A Randomized, Controlled, Double-Blind Trial
Kristoffer Berg-Hansen1, Kristian Hylleberg Christensen1, Nigopan Gopalasingam1
1Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
Insights
Exogenous ketone ester (KE) improved cardiac output and biventricular function in patients with cardiogenic shock (CS). This study suggests KE is a potential treatment for CS, enhancing tissue oxygenation and glycemic control.
Area of Science:
- Cardiology
- Metabolic Medicine
- Biochemistry
Background:
- Cardiogenic shock (CS) presents limited therapeutic avenues.
- The ketone body 3-hydroxybutyrate demonstrates beneficial hemodynamic effects in chronic heart failure.
- Hemodynamic effects of exogenous ketone ester (KE) in CS patients are not well understood.
Purpose of the Study:
- To evaluate the hemodynamic impact of a single enteral dose of KE in patients experiencing CS.
- To investigate the potential of KE as a novel therapeutic agent for CS.
Main Methods:
- A double-blind, crossover study involving 12 CS patients.
- Randomized administration of KE or placebo via enteral bolus.
- Comprehensive hemodynamic assessment using pulmonary artery catheterization, blood sampling, echocardiography, and near-infrared spectroscopy.
Main Results:
- KE significantly increased circulating 3-hydroxybutyrate levels.
- Augmented cardiac output, cardiac power output, and forearm perfusion were observed with KE.
- Improved left and right ventricular function, enhanced tissue oxygenation, and better glycemic control were noted.
Conclusions:
- Single-dose enteral KE administration improved key hemodynamic parameters in CS patients.
- KE demonstrated positive effects on biventricular function, oxygenation, and glucose metabolism.
- The findings support further investigation of KE for managing cardiogenic shock.
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).
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