ABSTRACT
Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from clinical and fundamental researches to identify its antiarrhythmic effects, reviewing the evidences and mechanism for the SGLT2i antiarrhythmic effects and establishing a novel paradigm involving intracellular sodium, metabolism and autophagy to investigate the potential mechanisms of SGLT2i in mitigating arrhythmias.
Subject(s)
Anti-Arrhythmia Agents , Arrhythmias, Cardiac , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Humans , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Anti-Arrhythmia Agents/therapeutic use , Anti-Arrhythmia Agents/adverse effects , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/prevention & control , Arrhythmias, Cardiac/metabolism , Treatment Outcome , Heart Rate/drug effects , Autophagy/drug effects , Sodium-Glucose Transporter 2/metabolism , Action Potentials/drug effects , Sodium/metabolismABSTRACT
Atrial fibrillation (AF) is a very common cardiac arrhythmia with an estimated prevalence of 33.5 million patients globally. It is associated with an increased risk of death, stroke and peripheral embolism. Although genetic studies have identified a growing number of genes associated with AF, the definitive impact of these genetic findings is yet to be established. Several mechanisms, including electrical, structural and neural remodelling of atrial tissue, have been proposed to contribute to the development of AF. Despite over a century of exploration, the molecular and cellular mechanisms underlying AF have not been fully established. Current antiarrhythmic drugs are associated with a significant rate of adverse events and management of AF using ablation is not optimal, especially in cases of persistent AF. This review discusses recent advances in our understanding and management of AF, including new concepts of epidemiology, genetics and pathophysiological mechanisms. We review the current status of antiarrhythmic drug therapy for AF, new potential agents, as well as mechanism-based AF ablation. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.