Impact of Sodium-glucose Cotransporter 2 Inhibitors on Echocardiography-derived Total Atrial Conduction Time

Abstract Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a new class of glucose-lowering agents. A large number of clinical trials have demonstrated that SGLT2 inhibitors improve the cardiovascular outcomes of type 2 diabetes mellitus (T2DM). Structural changes (increased fibrosis and hypertrophy) and electrical remodeling of the atria are among the myocardial changes induced by DM. Studies have shown that SGLT2 inhibitors reduce oxidative stress and improve mitochondrial function, thus reducing atrial fibrosis and hypertrophy. Echocardiography-derived total atrial conduction time (TACT) is a marker of atrial remodeling. TACT is calculated as the time delay between the onset of the P wave on an electrocardiogram and the peak A′ wave obtained from tissue Doppler imaging (PA-TDI duration). The aim of the present study was to investigate whether SGLT2 inhibitors reduce the TACTs of T2DM patients. Methods: This prospective, single-center pilot study was performed to evaluate the effects of additional treatment with SGLT2 inhibitors on the TACTs of T2DM patients. Between March 2022 and December 2022, 107 T2DM outpatients who had inadequately controlled were consecutively recruited from Gazi Yaşargil Training and Research Hospital, Diyarbakir, Turkey. All participants were evaluated at baseline and six months after commencing treatment with SGLT2 inhibitors. TACT was calculated as the mean time across six different regions between the onset of the P wave in lead II of an ECG and the peak A′ wave obtained from tissue Doppler imaging . Results: A total of 107 T2DM patients were included in the study. Among them, 57 were on dapagliflozin, and 50 were on empagliflozin. A univariate correlation analysis showed that the mean PA-TDI was correlated with Δ BMI (r = 0.094, p = 0.044) and Δ lateral E/e′ ratio (r = 0,312, p = 0.001). A multiple regression analysis revealed that Δ BMI and Δ lateral E/e′ ratio (p = 0.026 and p = 0.001, respectively) were inversely related to the mean PA-TDI duration. These findings remained after adjusting the Δ mean PA-TDI value for age and sex. Conclusion: This study showed for the first time that SGLT2 inhibitors can reduce TACT, likely by improving diastolic parameters and atrial remodeling and decreasing BMI.