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

Highlights •This study evaluated the impact of the sodium-glucose−linked co-transporter-2 inhibitor, empagliflozin, on cardiac function and structure in a nondiabetic model of heart failure with preserved ejection fraction in the deoxycorticosterone acetate salt-sensitive rat. •Deoxycorticosterone acetate rats developed hypertension, left ventricular hypertrophy, and diastolic dysfunction as measured by the time constant of relaxation, Tau. •Empagliflozin therapy, which did not significantly reduce blood pressure, increased hematocrit, reduced left ventricular and cardiomyocyte hypertrophy, and reduced wall stress, which led to improved diastolic function (shortening of Tau). •Empagliflozin treatment did not modify molecular markers of metabolism or hypertrophy, nor did it significantly affect key proteins involved in myocardial calcium handling. •This study concluded that the sodium-glucose−linked co-transporter-2 inhibitor, empagliflozin, in a nondiabetic model of heart failure with preserved ejection fraction improved cardiac diastolic function and reduced wall stress primary through a reduction in cardiac preload, and also altered hemodynamics.