Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic; Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, Rome, Italy.
Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.
Metabolism. 2021 Feb;115:154452. doi: 10.1016/j.metabol.2020.154452. Epub 2020 Nov 26.
Upregulation of ketone body (β-hydroxybutyrate, βHB) utilization has been documented in human end-stage heart failure (HF), but is unclear if this is due to intrinsic cardiac metabolic remodeling or a HF-related catabolic state. This study sought to evaluate the maximal ketone body utilization capacity and its determinants in controls and in patients with moderate HF and reduced ejection fraction (HFrEF).
19 HFrEF patients and 9 controls underwent sampling from the arterial circulation (A) and coronary sinus (CS) to measure transmyocardial extraction of energy-providing substrates and oxygen. In a separate experiment, measurements were performed 80-min after oral administration of 25 g of ketone ester (KE, (R)-3-hydroxybutyl(R)-3-hydroxybutyrate) drink in 11 HFrEF and 6 control subjects. There were no statistically significant differences in fasting substrate levels and fractional extractions between HF and controls. Administration of KE increased βHB by 12.9-fold, revealing an increased ability to utilize ketones in HFrEF as compared to controls (fractional extraction, FE%: 52 vs 39%, p = 0.035). βHB FE% correlated directly with βHB myocardial delivery (r = 0.90), LV mass (r = 0.56), LV diameter (r = 0.65) and inversely with LV EF (-0.59) (all p < 0.05). βHB FE% positively correlated with lactate FE% (p < 0.01), but not with FFA or glucose FE%, arguing against substrate competition.
Acute nutritional ketosis enhances βHB extraction in patients with HFrEF compared to controls, and this enhancement correlates with degree of cardiac dysfunction and remodeling. Data suggest that subclinical metabolic remodeling occurs early in HF progression. Further studies are needed to determine whether exogenous ketones may have a potential therapeutic role.
在人类终末期心力衰竭（HF）中已经记录到酮体（β-羟丁酸，βHB）利用的上调，但尚不清楚这是由于心脏内在代谢重塑还是 HF 相关的分解代谢状态。本研究旨在评估对照和中度 HF 伴射血分数降低（HFrEF）患者的最大酮体利用能力及其决定因素。
19 名 HFrEF 患者和 9 名对照者接受了从动脉循环（A）和冠状窦（CS）取样，以测量提供能量的底物和氧的跨心肌提取。在一项单独的实验中，在 11 名 HFrEF 和 6 名对照者口服 25g 酮酯（KE，（R）-3-羟丁酸（R）-3-羟丁酸）饮料 80 分钟后进行了测量。HF 和对照组之间空腹底物水平和分数提取没有统计学差异。KE 的给药使βHB 增加了 12.9 倍，表明 HFrEF 患者比对照组更能利用酮体（分数提取，FE%：52 对 39%，p=0.035）。βHB FE%与βHB 心肌输送直接相关（r=0.90），与 LV 质量（r=0.56）和 LV 直径（r=0.65）相关，与 LV EF 呈负相关（-0.59）（均 p<0.05）。βHB FE%与乳酸 FE%呈正相关（p<0.01），但与 FFA 或葡萄糖 FE%无关，这表明不存在底物竞争。
与对照组相比，急性营养性酮症增强了 HFrEF 患者的βHB 提取，并且这种增强与心脏功能障碍和重塑的程度相关。数据表明，亚临床代谢重塑在 HF 进展的早期就已经发生。需要进一步的研究来确定外源性酮体是否具有潜在的治疗作用。
