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Abstract P3149: Effect Of SGLT2 Inhibitors On Atrial Fibrillation Susceptibility In Diabetic Mice

Jonathan Granger, Pauline Nguyen, Olurotimi O. Mesubi

Circulation Research, 2023

Abstract

Background:

Diabetes mellitus (DM) and heart failure (HF) are independent risk factors for atrial fibrillation (AF), the commonest clinical arrhythmia. A new class of drugs - sodium glucose cotransporter 2 inhibitors (SGLT2i) have beneficial effect in DM and HF and are now part of the guideline directed therapy for HF. However, conflicting evidence exists regarding their role and effect on cardiac arrhythmias including AF independent of their effect on HF and their exact mechanism(s) of action on the heart.

Objective:

Here we tested the effect of two commonly used SGLT2i on AF susceptibility in a type 2 DM (T2D) mouse model.

Methods and Results:

We used a T2D mouse model (high fat diet + low dose streptozocin) and a cohort of T2D mice were treated with SGLT2i - Empagliflozin (30mg/kg/d) or Dapagliflozin (5mg/kg/d) for 10 weeks in drinking water. We performed invasive electrophysiologic studies (EPS) to assess AF susceptibility by a rapid atrial burst pacing protocol in male mice aged 5 months at the time of EPS. T2D mice had increased AF susceptibility compared with non-diabetic littermate controls (normal chow diet + citrate buffer) [78% (14/18) vs. 28% (5/18), p < 0.01]. T2D mice treated with Empagliflozin were protected from increased AF susceptibility (22% (3/18) [p < 0.01]) while T2D mice treated with Dapagliflozin were not protected from increased AF susceptibility (58% (11/19) [p = 0.29]). Both Empagliflozin and Dapagliflozin treated T2D mice had normalization of…

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