Guldbrandsen Halvor, Gopalasingam Nigopan, Christensen Kristian Hylleberg, Hørsdal Oskar Kjærgaard, Nielsen Roni, Wiggers Henrik, Berg-Hansen Kristoffer
Department of Cardiology Aarhus University Hospital Aarhus Denmark.
Department of Cardiology Viborg Regional Hospital Viborg Denmark.
J Am Heart Assoc. 2025 Jan 7;14(1):e038461. doi: 10.1161/JAHA.124.038461. Epub 2024 Dec 24.
Oral treatment with the exogenous ketone body 3-hydroxybutyrate improves cardiac function in patients with heart failure with reduced ejection fraction, but ketosis is limited to 3 to 4 hours. Treatment with (R)-1,3-butanediol (BD) provides prolonged ketosis in healthy controls, but the hemodynamic and metabolic profile is unexplored in patients with heart failure with reduced ejection fraction.
This was a randomized, single-blind, placebo-controlled, crossover study. Transthoracic echocardiography and venous blood samples were performed at baseline and hourly for 6 hours after an oral dose of BD (0.5 g/kg) or taste-matched placebo. The primary end point was the average between-treatment difference in cardiac output during the 6-hour period after intake. Secondary end points were stroke volume, heart rate, left ventricular ejection fraction, circulating 3-hydroxybutyrate, and free fatty acids. Twelve patients with heart failure with reduced ejection fraction were included. BD treatment provided significant increase in circulating 3-hydroxybutyrate by 1400 μmol/L (95% CI, 1262-1538 μmol/L, <0.001) and increased cardiac output by 0.9 L/min (95% CI, 0.7-1.1 L/min, <0.001) compared with placebo. Stroke volume increased by 15 mL (95% CI, 11-19 mL, <0.001), and heart rate remained similar between treatments (=0.150). Left ventricular ejection fraction increased by 3 percentage points (95% CI, 1-4 percentage points, <0.001). Global longitudinal strain improved (<0.001). Left ventricular contractility estimates increased after BD intake, and parameters of afterload were reduced. Finally, free fatty acids and glucose levels decreased.
Oral dosing of BD led to prolonged ketosis and cardiovascular and metabolic benefits in patients with heart failure with reduced ejection fraction. Treatment with BD is an attractive option to achieve beneficial effects from sustained therapeutic ketosis.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT05768100.
口服外源性酮体3-羟基丁酸可改善射血分数降低的心力衰竭患者的心脏功能，但酮症状态仅持续3至4小时。(R)-1,3-丁二醇（BD）治疗可使健康对照者的酮症持续时间延长，但在射血分数降低的心力衰竭患者中，其血流动力学和代谢情况尚未得到研究。
这是一项随机、单盲、安慰剂对照的交叉研究。在口服BD（0.5 g/kg）或口味匹配的安慰剂后，于基线及之后每小时进行一次经胸超声心动图检查和采集静脉血样本，共持续6小时。主要终点是服药后6小时内心输出量的组间平均差异。次要终点包括每搏输出量、心率、左心室射血分数、循环中的3-羟基丁酸和游离脂肪酸。纳入了12例射血分数降低的心力衰竭患者。与安慰剂相比，BD治疗使循环中的3-羟基丁酸显著增加1400 μmol/L（95% CI，1262-1538 μmol/L，P<0.001），心输出量增加0.9 L/min（95% CI，0.7-1.1 L/min，P<0.001）。每搏输出量增加15 mL（95% CI，11-19 mL，P<0.001），治疗组间心率保持相似（P=0.150）。左心室射血分数增加3个百分点（95% CI，1-4个百分点，P<0.001）。整体纵向应变改善（P<0.001）。口服BD后左心室收缩力评估增加，后负荷参数降低。最后，游离脂肪酸和葡萄糖水平下降。
口服BD可使射血分数降低的心力衰竭患者的酮症持续时间延长，并带来心血管和代谢方面的益处。BD治疗是通过持续治疗性酮症获得有益效果的一个有吸引力的选择。
