Key result
HFrEF and aortic stenosis are linked to increased cardiac ketone uptake versus controls.
Why the study?
Conflicting clinical data on FFA metabolism and limited knowledge on ketone body metabolism in human heart failure mandated additional metabolic profiling studies.
Is cardiac uptake of ketone bodies and free fatty acids altered in patients with HFrEF or aortic stenosis compared to controls?
Cross-Sectional (n=45)
No
Is cardiac uptake of ketone bodies and free fatty acids altered in patients with HFrEF or aortic stenosis compared to controls?
p-value: p=<0.05
Human heart failure and hypertrophic remodeling are associated with increased myocardial utilization of ketone bodies without apparent impairment in free fatty acid oxidation.
Increased ketone uptake in stable HFrEF and AS supports metabolic adaptation; leaves open whether ketolysis-targeted therapies alter outcomes.
BACKGROUND: Deranged energy metabolism contributes to the pathophysiology of heart failure (HF). Recent studies showed diminished free fatty acid (FFA) oxidation in experimental HF models with a shift towards oxidation of ketone bodies. However, conflicting clinical data on FFA metabolism and limited knowledge on ketone body metabolism in human HF mandate additional metabolic profiling studies. We, therefore, investigated cardiac uptake of FFAs and ketone bodies (β-hydroxybutyrate and acetoacetate) in patients with HF with reduced ejection fraction (HFrEF) or with aortic stenosis (AS)-induced left ventricular hypertrophy. We hypothesized that FFA oxidation is impaired in HFrEF and in AS and results in decreased concentrations of free carnitine, the necessary carrier for mitochondrial entry of activated FFAs, and in accumulation of metabolic intermediates. METHODS AND RESULTS: We collected arterial and coronary sinus blood samples in patients with HFrEF (n=15), in AS patients with preserved systolic function (n=15), and in control patients (n=15). Plasma concentration gradients across the heart show significantly greater uptake of ketone bodies in patients with HFrEF than in controls. Patients with AS show significantly increased uptake of β-hydroxybutyrate and FFAs. Free carnitine concentration and concentration gradients of intermediates of FFA oxidation were comparable between groups. CONCLUSIONS: In conclusion, our results show significantly increased cardiac uptake of ketone bodies in patients with stable HFrEF and AS and increased uptake of FFAs in AS compared with control patients. The lack of myocardial release of acyl-carnitine species or change in free carnitine uptake suggests no impairment of FFA oxidation.
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Vörös et al. (2018) conducted a cross-sectional in Heart Failure with reduced Ejection Fraction (HFrEF) and Aortic Stenosis (n=45). Heart failure and left ventricular hypertrophy vs. Patients with a morphologically normal heart was evaluated on Cardiac uptake (arterial-coronary sinus concentration gradients) of ketone bodies and free fatty acids (p=<0.05). Patients with stable heart failure with reduced ejection fraction or aortic stenosis had significantly increased cardiac uptake of ketone bodies, while aortic stenosis patients also had increased uptake of free fatty acids compared to controls.
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