Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF.

Aims: Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodelling and atrial fibrillation are frequently observed in HFpEF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial anti-arrhythmic effects.

Cardioprotection by SGLT2 Inhibitors-Does It All Come Down to Na?

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are emerging as a new treatment strategy for heart failure with reduced ejection fraction (HFrEF) and-depending on the wistfully awaited results of two clinical trials (DELIVER and EMPEROR-Preserved)-may be the first drug class to improve cardiovascular outcomes in patients suffering from heart failure with preserved ejection fraction (HFpEF). Proposed mechanisms of action of this class of drugs are diverse and include metabolic and hemodynamic effects as well as effects on inflammation, neurohumoral activation, and intracellular ion homeostasis. In this review we focus on the growing body of evidence for SGLT2i-mediated effects on cardiac intracellular Na as an upstream mechanism.

Empagliflozin inhibits Na /H exchanger activity in human atrial cardiomyocytes.

Aims: Recent clinical trials have proven gliflozins to be cardioprotective in diabetic and non-diabetic patients. However, the underlying mechanisms are incompletely understood. A potential inhibition of cardiac Na /H exchanger 1 (NHE1) has been suggested in animal models.