Center for Cardiovascular Research (CCR), Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charité University Medicine, Augustenburgerplatz 1, 13353 Berlin, Germany.
German Center for Cardiovascular Research (DZHK), Partner Site Berlin, 13353 Berlin, Germany.
Int J Mol Sci. 2021 May 31;22(11):5937. doi: 10.3390/ijms22115937.
Atrial fibrillation (AF) is the most common sustained (atrial) arrhythmia, a considerable global health burden and often associated with heart failure. Perturbations of redox signalling in cardiomyocytes provide a cellular substrate for the manifestation and maintenance of atrial arrhythmias. Several clinical trials have shown that treatment with sodium-glucose linked transporter inhibitors (SGLTi) improves mortality and hospitalisation in heart failure patients independent of the presence of diabetes. Post hoc analysis of the DECLARE-TIMI 58 trial showed a 19% reduction in AF in patients with diabetes mellitus (hazard ratio, 0.81 (95% confidence interval: 0.68-0.95), n = 17.160) upon treatment with SGLTi, regardless of pre-existing AF or heart failure and independent from blood pressure or renal function. Accordingly, ongoing experimental work suggests that SGLTi not only positively impact heart failure but also counteract cellular ROS production in cardiomyocytes, thereby potentially altering atrial remodelling and reducing AF burden. In this article, we review recent studies investigating the effect of SGLTi on cellular processes closely interlinked with redox balance and their potential effects on the onset and progression of AF. Despite promising insight into SGLTi effect on Ca cycling, Na balance, inflammatory and fibrotic signalling, mitochondrial function and energy balance and their potential effect on AF, the data are not yet conclusive and the importance of individual pathways for human AF remains to be established. Lastly, an overview of clinical studies investigating SGLTi in the context of AF is provided.
心房颤动（AF）是最常见的持续性（心房）心律失常，是一个相当大的全球健康负担，通常与心力衰竭有关。心肌细胞中氧化还原信号的紊乱为心房性心律失常的表现和维持提供了细胞基础。几项临床试验表明，钠-葡萄糖共转运蛋白抑制剂（SGLTi）的治疗可改善心力衰竭患者的死亡率和住院率，而与糖尿病的存在无关。DECLARE-TIMI 58 试验的事后分析显示，糖尿病患者在接受 SGLTi 治疗后，AF 减少了 19%（危险比，0.81（95%置信区间：0.68-0.95），n = 17160），无论是否存在预先存在的 AF 或心力衰竭，并且独立于血压或肾功能。因此，正在进行的实验工作表明，SGLTi 不仅对心力衰竭有积极影响，而且还能抑制心肌细胞中 ROS 的产生，从而可能改变心房重构并减少 AF 的负担。在本文中，我们回顾了最近研究 SGLTi 对与氧化还原平衡密切相关的细胞过程的影响及其对 AF 发生和进展的潜在影响。尽管 SGLTi 对 Ca 循环、Na 平衡、炎症和纤维化信号、线粒体功能和能量平衡及其对 AF 的潜在影响有了有希望的了解，但数据尚不确定，个体途径对人类 AF 的重要性仍有待确定。最后，提供了研究 SGLTi 在 AF 背景下的临床研究概述。
