Glycemic

Heart failure with preserved ejection fraction

Preload

Ejection fraction

Blood pressure

Endocrinology

Insulin

Cardiology

Type 2 diabetes

Diastole

Hemodynamics

Ranolazine

Internal medicine

Empagliflozin

Heart failure

Diabetes mellitus

Afterload

Rodent model

Medicine

JACC Basic to Translational Science

Recent studies send an unambiguous signal that the class of agents known as sodium-glucose–linked co-transporter-2 inhibitors (SGLT2i) prevent heart failure hospitalization in patients with type 2 diabetes. However, the mechanisms remain unclear. Herein the authors utilize a rodent model of heart failure with preserved ejection fraction (HFpEF), and demonstrate that treatment with the SGLT2i empagliflozin, reduces left ventricular mass, improving both wall stress and diastolic function. These findings extend the observation that the main mechanism of action of empagliflozin involves improved hemodynamics (i.e., reduction in preload and afterload) and provide a rationale for upcoming trials in patients with HFpEF irrespective of glycemic status.

Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With Preserved Ejection Fraction