Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects (KETO-KINETICS1)

Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects

Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects

The ketone body 3-hydroxybutyrate (3-OHB) is a naturally occurring energy substrate, and is associated with increased life span and improved health. We have previously shown that intravenous 3-OHB treatment increases myocardial blood flow > 70% in healthy humans and data from our group show that 3-OHB increases cardiac output by 40 % in patients with heart failure. In this study the investigators aim to investigate: If this effect is reproducible with a commercially available oral ketone supplements The safety of commercially available ketone supplements in heart failure patients

Heart Failure (HF) is a major public health issue because the disease affects 1-2% of the Western population and the lifetime risk of HF is 20%. HF is responsible for 1-2% of all healthcare expenditures. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is 13 % and >50% of HF-patients is admitted during a 2.5 year period. 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. Ketone bodies are produced in the liver and are of vital importance in the human body for energy generation in the heart and brain during fasting, exercise and severe illness. Ketosis can be safely obtained using dietary supplements and can increase exercise capacity in athletes. The most important ketone bodies are 3-hydroxybutyrate (3-OHB) and acetoacetate. Recently, it was demonstrated that patients with severe HF have increased myocardial utilization of the ketone body 3-hydroxybutyrate. We have shown, using positron emission tomography, that ketone body infusion reduces myocardial glucose uptake and increases myocardial blood flow in healthy subjects. Data from another study conducted by our group show a 40% increase in cardiac output during infusion of 3-OHB. Presently there are no data on the clinical cardiovascular and metabolic effects of long-term oral ketone-supplementation in patients with chronic HF. In this study the investigators will whether ketosis obtained by oral ketone supplements affects hemodynamics and contractile function.

Cross-over study in 8 patients receiving single-dose oral 3-hydroxybutyrate monoester, 3-OHB salt and placebo.

Comercially available carbohydrate sports drink. The placebo dose is isocaloric to the 3-hydroxy butyrate dose.

Inclusion Criteria: Chronic Heart Failure; NYHA class II-III Left Ventricular Ejection Fraction <40% Exclusion Criteria: Diabetes or HbA1c > 48 mmol/mol Significant cardiac valve disease, Severe stable angina pectoris Severe comorbidity as judged by investigator, Inability to give informed consent.