Empagliflozin Ameliorates Atrial and Ventricular Remodeling and Arrhythmogenesis in an Overweight Rabbit Model

Overweight is associated with dysrhythmia and sudden cardiac death, while sodium glucose co-transporter-2 inhibitors (SGLT2-is) have been shown to possess cardioprotective effects in patients with hyperglycemia. Objectives: The

Overweight causes atrial and ventricular remodeling with prolongation of effective refractoriness, increased vulnerability to VF induction, upregulation of calcium handling proteins, and advanced fibrosis. Empagliflozin attenuates these remodeling effects, leading to decreased cardiac arrhythmogenicity and a reduced risk of sudden cardiac death.

Twenty-four rabbits were randomized into 4 groups: controls (Group 1), high-fat diet (HFD) (Group 2), controls treated with empagliflozin (Group 3), and HFD treated with empagliflozin (Group 4). All rabbits underwent electrophysiologic studies and ventricular tachycardia/ventricular fibrillation (VF) inducibility tests (maximal output with shortest 1:1 cycle length pacing). Atrial and ventricular myocardium were harvested for Western blot and Trichrome staining.

Among all groups, Group 2 had the longest atrial effective refractory periods (ERPs) in both left and right atria, as well as the longest ventricular ERPs in both left and right ventricles. VF inducibility was highest in Group 2. The degree of fibrosis in both atria and ventricles was most severe in Group 2 and similar to that in Group 4. Enhanced calcium handling protein (CaV 1.2) expressions were noted in Group 2 compared to those in Group 1 and Group 3, respectively, and returned to baseline in Group 4. Conclusions: Overweight causes atrial and ventricular remodeling with prolongation of effective refractoriness, increased vulnerability to VF induction, upregulation of calcium handling proteins, and advanced fibrosis. Empagliflozin attenuates these remodeling effects, leading to decreased cardiac arrhythmogenicity and a reduced risk of sudden cardiac death.