Sodium-Glucose Co-transporter 2 Inhibitors in Patients with Heart Failure with Preserved Ejection Fraction: Proposed Mechanisms, Recent Evidence, and Clinical Implications.

Heart failure (HF) affects approximately 6 million Americans and is projected to increase in prevalence as the population ages. While progress has been made in the treatment of heart failure with reduced ejection fraction (HFrEF), treatments for heart failure with preserved ejection fraction (HFpEF) are few and far between. Since HFpEF makes up half of all heart failure cases, its management may be the biggest unmet need in cardiology. Results from the recent EMPEROR-Preserved trial are encouraging. After 26 months, patients with HFpEF who used the sodium-glucose co-transporter 2 inhibitor empagliflozin had a lower risk of hospitalization for HF than patients taking a placebo. However, the trial did not show empagliflozin to reduce the risk of cardiovascular death, unlike the EMPEROR-Reduced trial, in which empagliflozin was associated with a reduced risk of both cardiac death and hospitalization for patients with HFrEF. The outcomes of these trials highlight the dissimilarities between the two diseases. While HFrEF is mainly a disease of cardiomyocyte injury and systolic dysfunction, HFpEF is a multifactorial syndrome of inflammation and endothelial dysfunction stemming from chronic diseases like hypertension, diabetes and obesity. While trials of empagliflozin for HFpEF did not show a mortality benefit, sodium-glucose co-transporter 2 inhibitors are promising additions to the management of HFpEF for their effects on the disease's risk factors through weight loss, natriuresis, blood pressure lowering, and glycemic control.