Key result
SGLT inhibitors may reduce AF burden by suppressing reactive oxygen species, though clinical data remain inconclusive.
Why the study?
Data on how SGLTi affect redox balance and cellular processes linked to AF onset and progression are inconclusive, and the importance of individual pathways remains to be established.
This review highlights the potential mechanistic pathways by which SGLT inhibitors might prevent or reduce atrial fibrillation through modulation of redox signaling, cellular ion homeostasis, and inflammation.
Supports mechanistic plausibility for SGLT inhibitors in AF; hypothesis-generating and should not change practice pending trials.
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 Ca2+ 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.
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Bode et al. (2021) conducted a review in Atrial fibrillation. Sodium-glucose linked transporter inhibitors (SGLTi) was evaluated. Sodium-glucose linked transporter inhibitors potentially reduce atrial fibrillation burden by counteracting cellular reactive oxygen species production, though conclusive human clinical trial data are still lacking.
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