Hemodynamic Effects of Modulating Circulating Ketone Bodies With 1,3-butanediol (KETO-BD)

Heart Failure (HF) is a major public health issue affecting 1-2% of the Western population and the lifetime risk of HF is 20%. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is high. Furthermore, patients with HF have markedly decreased physical capacity and quality of life. Thus, there is a need for new treatment modalities in this group of patients. In a first-in-man study we have recently discovered that 3-OHB-infusion increases cardiac output by 2 L/min (40% relative increase) and left ventricular (LV) ejection fraction (LVEF) by 8% in absolute numbers in patients with HF and reduced LVEF (HFrEF). 1,3-Butanediol (BD) serves as a potential nutritional supplement in providing long-lasting ketosis as a treatment option in heart disease. Whether BD provides similar hemodynamic effects as ketone monoester remains unknown. Hypothesis Oral BD increases cardiac output and LV function in patients with HFrEF. Aims To investigate the acute hemodynamic effects of weight-adjusted oral BD supplements in patients with HFrEF. Design In a randomized, single-blind, placebo-controlled, crossover design, 12 patients with HFrEF are studied following overnight fast on 2 separate visits in random order: 1) during intake of BD (HVMN, San Francisco, California, USA) and during placebo. Methods Transthoracic echocardiography, non-invasive blood pressure, and venous blood samples are obtained every 60 minutes from baseline until 6 hours following BD ingestion.

Inclusion Criteria: Chronic HF: NYHA class II-III, LVEF <40%. Negative urine-HCG for women with childbearing potential. Age ≥18 years. Exclusion Criteria: Diabetes or HbA1c >48 mmol/mol, significant cardiac valve disease, severe stable angina pectoris, severe comorbidity as judged by the investigator, inability to give informed consent.