Targeting atrial myopathy: Dose dependent manner of SGLT2 inhibitor in preventing electrical and structural remodelling in metabolic syndrome rat model

Abstract Background and Aims Atrial myopathy, a substrate for atrial fibrillation (AF) driven by structural and electrophysiological remodeling, is closely linked to metabolic syndrome (MetS). Empagliflozin (EMPA), an SGLT2 inhibitor with established cardioprotective properties, has not been fully evaluated in the context of atrial myopathy. This study examined its dose-dependent atrial effects in a Wistar rat MetS model. Methods Twenty-four male Wistar rats were allocated into four groups (n=6): healthy controls, MetS (high-fat high-sugar diet with streptozotocin over 16 weeks), MetS + EMPA 10 mg/kg/day, and MetS + EMPA 30 mg/kg/day. Under standardized anesthesia, surface ECG, echocardiography, and transesophageal electrophysiology studies were performed to assess P wave duration, left atrial (LA) length and area, isovolumetric relaxation time (IVRT), atrial effective refractory period (AERP), and corrected sinus node recovery time (CSNRT). Results MetS significantly prolonged P wave duration (p=0.0057), enlarged LA length (p=0.0022) and area (p=0.0073), elevated IVRT (35.60 vs. 19.19 ms; p<0.0001), and shortened AERP (p=0.0106) compared to controls. Both EMPA doses attenuated P wave prolongation and LA dilation. AERP was significantly preserved in the EMPA 10 mg/kg/day group versus MetS (p=0.0356). CSNRT differed significantly across groups (p=0.0468), without reaching pairwise significance after adjustment. Conclusion MetS induces multidimensional atrial myopathy encompassing structural dilation, diastolic dysfunction, conduction delay, and abbreviated refractoriness. Empagliflozin attenuated these alterations in a partially dose-dependent manner, supporting its candidacy as a preventive strategy against MetS-related AF.Figure 1.(A) Electrophysiological Tracings, (B) Echocardiography