Effects of 2-week Ketosis on the Heart's Ketone Body Consumption, Utilization, and Energetic Efficiency in Patients With Chronic Heart Failure - Trial NCT06398964

Timeline & Enrollment

Primary Outcome

Myocardial consumption of 3-OHB.

Summary

Heart Failure (HF) is a significant health concern, affecting around 1-2% of people in
 Western countries. The risk of developing HF during a lifetime is about 20%. Despite
 advancements in HF care, the one-year mortality rate for HF patients remains high. HF
 patients also experience reduced physical capacity and quality of life. The heart relies
 heavily on a process called oxidative metabolism for energy, and this process requires a
 continuous supply of energy sources like fatty acids, glucose, and ketone bodies. In HF,
 there's a shift in how the heart uses these energy sources, which affects its efficiency.
 
 Ketone bodies such as 3-OHB, are molecules that can provide the heart with a more efficient
 energy source compared to traditional ones like fatty acids or glucose. They are produced in
 the liver and are important for supplying energy during fasting, exercise, and illness.
 Recent research suggests that 3-OHB might have benefits for HF patients beyond just providing
 energy. It seems to reduce inflammation and oxidative stress in the heart. Some studies in
 healthy individuals have shown that infusing 3-OHB increases blood flow to the heart.
 
 In HF patients, the investigators aim to explore the cardiac effects of a two-week supplement
 of 3-OHB. The aim is to investigate if this supplement can increase the heart's consumption
 and utilization of 3-OHB. The study involves 12 patients with HF and reduced ejection
 fraction (HFrEF). The patients will receive a ketone ester supplement four times a day for
 two weeks, and then they'll take an isocaloric placebo supplement for another two weeks.
 
 The investigators will use positron emission tomography (PET) to study the cardiac oxygen
 consumption and 3-OHB uptake. This is done by injection of tracers (11-C-3-OHB and
 11-C-acetate).
 
 The study will also look at myocardial external efficiency (MEE) and myocardial blood flow
 (MBF). For a subset of participants, the investigators will also take myocardial biopsies and
 perform more detailed analyses, e.g. respirometry and electron microscopy or single nucleus
 mRNA sequencing, proteomics and metabolimcs, to understand the impact of the supplement on
 the heart's cellular structures and functions, transcriptome, proteome and metabolome.
 
 Ultimately, this study aims to determine whether supplementing HF patients with 3-OHB can
 improve the heart's energy usage and potentially provide other beneficial effects. This
 research might pave the way for new treatments that enhance the heart's function and quality
 of life for HF patients.

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