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.

中文翻译：

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人心力衰竭和肥厚性左心室重构中酮体和游离脂肪酸对心脏吸收的增加

背景：能量代谢紊乱有助于心力衰竭（HF）的病理生理。最近的研究表明，在实验性HF模型中，游离脂肪酸（FFA）的氧化作用逐渐减弱，并逐渐向酮体的氧化转变。然而，有关HFA代谢的临床数据相互矛盾，以及人类HF中酮体代谢的知识有限，因此需要进行其他代谢谱研究。因此，我们研究了射血分数降低（HFrEF）或主动脉瓣狭窄（AS）引起的左心室肥厚的HF患者的FFA和酮体（β-羟基丁酸酯和乙酰乙酸酯）的心脏摄取。我们假设HFrEF和AS中的FFA氧化受到损害，并导致游离肉碱的浓度降低，游离肉碱是激活的FFA线粒体进入所必需的载体，方法和结果：我们收集了HFrEF患者（n = 15），收缩功能保留的AS患者（n = 15）和对照组（n = 15）的动脉和冠状窦血样。 ）。与对照组相比，HFrEF患者心脏中的血浆浓度梯度显着增加了酮体的摄取。AS患者显示出β-羟基丁酸酯和FFA的摄取显着增加。结论：总之，我们的结果表明，与对照组相比，HFrEF和AS稳定的患者酮体的心脏摄取量显着增加，AS中FFA的摄取量显着增加。