This dissertation of Suzanne Voorrips 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 exercise intolerance. In HFpEF, the pathophysiology of exercise intolerance remains incompletely understood.
This dissertation includes a clinical study in patients with HFpEF which shows that - in contrast to patients with HFrEF - only a minority of patients exhibits a deficient energy balance or increased skeletal muscle acidification during exercise. Furthermore, another study in this dissertation examined the effectiveness of ketone body treatment during exercise in HFrEF. This study showed that ketone body treatment did not therapeutically benefit skeletal muscle energy metabolism during exercise in HFrEF.
Nevertheless, an experimental study ivnestigating whether the protective effects of sodium-glucose co-transporter (SGLT2) inhibitors in heart failure are driven by an increase in cardiac ketone body oxidation, showed that ketone body metabolism does contribute at least partly to the protective effects of SGLT2 inhibitors in heart failure treatment.
Moreover, an analysis of ketone body metabolism in patients during an episode of acute heart failure showed that ketone body levels, and acetone in particular, were elevated in the 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.
