EMPA-VISION: Cardiac energy in people with heart failure taking empagliflozin

As the prevalence of heart failure (HF) has increased, so too has the need for new treatments for the condition. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have emerged in recent years as a treatment for both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). 

Although it has been hypothesised that SGLT2i treatment may lead to a myocardial substrate switch that improves energy production, a definite cardiac mechanism has remained unclear. The randomised, controlled EMPA-VISION trial primarily aimed to assess the effects of empagliflozin on cardiac energetics.

Two cohorts were enrolled, one with HFrEF (left-ventricular ejection fraction [LVEF] ≤40%; n=36) and the other with HFpEF (LVEF ≥50%; n=36), and randomly assigned to empagliflozin 10 mg or placebo once daily for 12 weeks. The primary endpoint was a change from baseline in cardiac phosphocreatine:ATP ratio (PCr:ATP), a sensitive marker of the overall energetic state of the heart. This was determined at rest and during peak stress (65% of age-maximum heart rate). Mass spectrometry on a set of 19 serum metabolites associated with energy metabolism was also performed at baseline and 12 weeks.

The study found that empagliflozin did not change PCr:ATP at rest or during stress in either HFrEF or HFpEF, compared to placebo. Furthermore, no significant changes were observed in serum metabolomics or levels of circulating ketone bodies in either cohort. The results do not, therefore, support the hypothesis that improved energy provision is responsible for the beneficial clinical effects of SGLT2i treatment in HF. 

The full study can be read here.