Improving exercise tolerance and energy metabolism in heart failure

This dissertation includes several studies on exercise capacity and energy metabolism in patients with heart failure, approaching heart failure treatment from a metabolic perspective. Heart failure can broadly be divided into two types based on reduced (HFrEF) or preserved (HFpEF) pumping function of the heart. Both types are characterized by a reduced exercise tolerance. This dissertation includes an observational, prospective study in eighteen patients with HFpEF and six healthy controls which shows that only a minority of patients with HFpEF exhibits a deficient energy balance or increased skeletal muscle acidification during exercise. A placebo-controlled, randomized trial in fourteen patients with HFrEF examined the effectiveness of ketone body treatment during exercise. In this study, using a cross-over design, ketone bodies were found to provide no therapeutic benefit to skeletal muscle energy metabolism during exercise. Nevertheless, an experimental study, investigating whether the protective effects of sodium-glucose co-transporter (SGLT2) inhibitors in heart failure are driven by an increase in cardiac ketone body oxidation, shows that ketone body metabolism contributes at least partly to the protective effects of SGLT2 inhibitors in heart failure treatment. Finally, an analysis of ketone body metabolism in patients during an episode of acute heart failure shows that ketone body levels, and particularly acetone, are elevated in this setting of acute heart failure. Future research could reveal whether and to what extent ketone bodies can play a role in the treatment of heart failure and to what extent they could be of prognostic value.