Acute antiarrhythmic effects of SGLT2 inhibitors–dapagliflozin lowers the excitability of atrial cardiomyocytes

• DOI: 10.1007/s00395-023-01022-0
• Publication Date: 2024-01-03T11:01:50Z
• Authors: Amelie Paasche; Felix Wiedmann; Manuel Kraft; Fitzwilliam Seibertz; Valerie Herlt; Pablo L. Blochberger; Natasa Jávorszky; Moritz Beck; Leo Weirauch; Timon Seeger; Antje Blank; Walter E. Haefeli; Rawa Arif; Anna L. Meyer; Gregor Warnecke; Matthias Karck; Niels Voigt; Norbert Frey; Constanze Schmidt
• Keywords: Dapagliflozin; Cardiac Electrophysiology; Proarrhythmia

Abstract In recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection been identified. this study, we place special emphasis on the atria investigate acute electrophysiological effects dapagliflozin assess antiarrhythmic potential inhibitors. Direct were investigated in patch clamp experiments isolated atrial cardiomyocytes. Acute treatment with elevated-dose caused a significant reduction action inducibility, amplitude maximum upstroke velocity. The inhibitory reproduced human induced pluripotent stem cell-derived cardiomyocytes, more pronounced compared ventricular cells. Hypothesizing that directly affects depolarization phase potentials, examined fast inward sodium currents cardiomyocytes found decrease peak current densities by dapagliflozin, accompanied moderate inhibition transient outward potassium current. Translating these findings into porcine large animal model, atrial-dominant myocardial conduction velocity vivo. This could be utilized for both, cardioversion paroxysmal fibrillation episodes rhythm control persistent fibrillation. show alters excitability direct currents. vivo , exerts effects, revealing new additional role arrhythmias.