Clinical Trial: Ketones in Heart Failure - Effects on Cardiac Efficiency

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effects of Ketones on Cardiac Function and Oxygen Consumption in Heart Failure Patients With Reduced Ejection Fraction and Healthy Test Subjects

Brief Summary: Ketones may have beneficial effects on myocardial metabolism and hemodynamics. In the present study, healthy test subjects and patients with heart failure with reduced ejections fraction will be investigated in a randomized cross-over design with ketone infusions and placebo. Myocardial efficiency and hemodynamics will be evaluated.

Detailed Summary:

The prevalence of patients with heart failure and reduced ejection fraction (HFrEF) is 1-2%, and the lifetime risk of heart failure at age 55 years is approximately 30%. Despite advances in treatment, hospitalization rate and mortality remains high. It is well known that myocardial metabolism changes during development of HFrEF, and may contribute to contractile dysfunction. However, the myocardium can be considered an omnivore regarding substrate utilization, conferring an important adaptive property. Hence, it metabolizes either glucose, lipids, lactate, amino acids or ketones (3-hydroxybutyrate) depending on substrate availability, hormonal status and cardiac demands. These substrates differ with regard to myocardial energy efficiency (MEE) (cardiac work related to oxygen consumption). Since high MEE is associated with a better prognosis in HFrEF, manipulating substrate uptake could be a new treatment modality in heart failure patients.

Recently, it was shown that the human myocardium increases 3-hydroxybutyrate (3-OHB) metabolism during development of HFrEF. These changes may be beneficial as 3-OHB could increase myocardial efficiency and lower oxidative stress by scavenging free radicals. However, until now this has not been investigated in clinical trials, and the effect of 3-OHB on cardiac function, oxygen consumption and perfusion remains undetermined in HFrEF patients.

In the present study the investigators will evaluate whether elevated circulating 3-OHB affect myocardial oxygen consumption, MEE and perfusion in healthy subjects and patients with HFrEF, and whether 3-OHB affect hemodynamics and contractile function.

10 healthy test subjects and 20 HFrEF patients will be subjected to placebo and 3-OHB infusion in a randomized cross-over design. Acetate-PET, echocar
Sponsor: University of Aarhus

Current Primary Outcome:

  • Myocardial efficiency [ Time Frame: 1 day ]
    Based on myocardial PET examinations
  • Cardiac output [ Time Frame: 1 day ]
    Right sided heart catheterization


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Myocardial perfusion [ Time Frame: 1 day ]
    Based on myocardial PET examinations
  • Myocardial oxygen consumption [ Time Frame: 1 day ]
    Based on myocardial PET examinations
  • Pulmonary and wedge pressure [ Time Frame: 1 day ]
    Right sided heart catheterization
  • Mixed venous saturation [ Time Frame: 1 day ]
    Right sided heart catheterization


Original Secondary Outcome: Same as current

Information By: University of Aarhus

Dates:
Date Received: February 20, 2017
Date Started: March 17, 2017
Date Completion: May 1, 2018
Last Updated: March 31, 2017
Last Verified: January 2017