Treatment with ketone ester in patients with acute heart failure improves cardiac performance - a randomized, clinical study

Acute heart failure (AHF) is associated with high morbidity and mortality with limited evidence-based treatments. Recent studies suggest that the ketone body 3-hydroxybutyrate (3-OHB) has beneficial hemodynamic effects in patients with stable chronic heart failure and cardiogenic shock. However, the hemodynamic effects of exogenous ketone supplementation in patients with AHF without cardiogenic shock remain unknown.

Hypothesis: In patients hospitalized with AHF, treatment with a single dose of ketone ester (KE) has beneficial hemodynamic effects.

In a randomized, single-blind, crossover study, we included 12 patients hospitalized with AHF who had reduced left ventricular ejection fraction (LVEF ≤40%) and were treated with IV diuretics. In random order, patients received an oral bolus of 500 mg/kg ketone ester and isocaloric, isovolemic placebo containing maltodextrin. Each study period lasted for three hours and was separated by a three-hour washout period. Invasive hemodynamic monitoring was performed with a pulmonary artery catheter. The primary endpoint was the average pairwise difference in cardiac output, measured by thermodilution, during the three-hour treatment period after ketone ester versus placebo. Secondary endpoints included changes in pulmonary artery wedge pressure (PAWP) and mixed venous saturation (SVO2).

Plasma 3-OHB increased markedly following KE administration (3.8 ± 1.9 mmol/L vs. 0.2 ± 0.2 mmol/L; p <0.001) during the three-hour study period. Cardiac output increased by 0.3 L/min (95%CI: 0.1 to 0.5 L/min, p=0.013) through the three-hour period, accompanied by higher SVO2 (69±9% vs. 64±10%; p <0.001) and increased stroke volume (59±17 mL vs. 55±17 mL; p = 0.003). Heart rate decreased slightly (−2.7 bpm, p = 0.028). Filling pressures were lower after KE administration: PAWP (-4 mmHg; 95%CI: -6 to -3 mmHg; p <0.001) and right atrial pressure (-2 mmHg; 95%CI: -3 to -1 mmHg; p <0.001). Mean arterial pressure and systemic vascular resistance were not significantly different between treatments, while the afterload parameter arterial elastance decreased by -0.2 mmHg/mL (95%CI: -0.4 to -0.1; p = 0.008).

In patients hospitalized with AHF, a single oral dose of oral KE improved cardiac output and peripheral perfusion and reduced cardiac filling pressures. These findings suggest that exogenous ketone supplementation may represent a promising treatment in patients with AHF.

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