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Benefits of SGLT2 inhibitors in arrhythmias.

ABSTRACT: Some studies have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors can definitively attenuate the occurrence of cardiovascular diseases such as heart failure (HF), dilated cardiomyopathy (DCM), and myocardial infarction. With the development of research, SGLT2 inhibitors can also reduce the risk of arrhythmias. So in this review, how SGLT2 inhibitors play a role in reducing the risk of arrhythmia from the perspective of electrical remodeling and structural remodeling are explored and then the possible mechanisms are discussed. Specifically, we focus on the role of SGLT2 inhibitors in Na⁺ and Ca^{2 +} homeostasis and the transients of Na⁺ and Ca^{2 +}, which could affect electrical remodeling and then lead to arrythmia. We also discuss the protective role of SGLT2 inhibitors in structural remodeling from the perspective of fibrosis, inflammation, oxidative stress, and apoptosis. Ultimately, it is clear that SGLT2 inhibitors have significant benefits on cardiovascular diseases such as HF, myocardial hypertrophy and myocardial infarction. It can be expected that SGLT2 inhibitors can reduce the risk of arrhythmia.

SUBMITTER: Gao J

PROVIDER: S-EPMC9631490 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Benefits of SGLT2 inhibitors in arrhythmias.

Gao Jinghan J Xue Genlong G Zhan Ge G Wang Xinying X Li Jiatian J Yang Xiaolei X Xia Yunlong Y

Frontiers in cardiovascular medicine 20221020

Some studies have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors can definitively attenuate the occurrence of cardiovascular diseases such as heart failure (HF), dilated cardiomyopathy (DCM), and myocardial infarction. With the development of research, SGLT2 inhibitors can also reduce the risk of arrhythmias. So in this review, how SGLT2 inhibitors play a role in reducing the risk of arrhythmia from the perspective of electrical remodeling and structural remodeling are explored and ...[more]

PMID: 36337862

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Project description:SGLT2 inhibitors have profound benefits on reducing heart failure and cardiovascular mortality in individuals with type 2 diabetes, although the mechanism(s) of this benefit remain poorly understood. Because changes in cardiac bioenergetics play a critical role in the pathophysiology of heart failure, the authors evaluated cardiac energy production and substrate use in diabetic mice treated with the SGTL2 inhibitor, empagliflozin. Empagliflozin treatment of diabetic db/db mice prevented the development of cardiac failure. Glycolysis, and the oxidation of glucose, fatty acids and ketones were measured in the isolated working heart perfused with 5 mmol/l glucose, 0.8 mmol/l palmitate, 0.5 mmol/l ß-hydroxybutyrate (ßOHB), and 500 μU/ml insulin. In vehicle-treated db/db mice, cardiac glucose oxidation rates were decreased by 61%, compared with control mice, but only by 43% in empagliflozin-treated diabetic mice. Interestingly, cardiac ketone oxidation rates in db/db mice decreased to 45% of the rates seen in control mice, whereas a similar decrease (43%) was seen in empagliflozin-treated db/db mice. Overall cardiac adenosine triphosphate (ATP) production rates decreased by 36% in db/db vehicle-treated hearts compared with control mice, with fatty acid oxidation providing 42%, glucose oxidation 26%, ketone oxidation 10%, and glycolysis 22% of ATP production in db/db mouse hearts. In empagliflozin-treated db/db mice, cardiac ATP production rates increased by 31% compared with db/db vehicle-treated mice, primarily due to a 61% increase in the contribution of glucose oxidation to energy production. Cardiac efficiency (cardiac work/O2 consumed) decreased by 28% in db/db vehicle-treated hearts, compared with control hearts, and empagliflozin did not increase cardiac efficiency per se. Because ketone oxidation was impaired in db/db mouse hearts, the authors determined whether this contributed to the decrease in cardiac efficiency seen in the db/db mouse hearts. Addition of 600 μmol/l ßOHB to db/db mouse hearts perfused with 5 mmol/l glucose, 0.8 mmol/l palmitate, and 100 μU/ml insulin increased ketone oxidation rates, but did not decrease either glucose oxidation or fatty acid oxidation rates. The presence of ketones did not increase cardiac efficiency, but did increase ATP production rates, due to the additional contribution of ketone oxidation to energy production. The authors conclude that empagliflozin treatment is associated with an increase in ATP production, resulting in an enhanced energy status of the heart.

Project description:BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promise in improving cardiovascular outcome in patients with heart failure (HF) and diabetes mellitus (DM). Although these benefits have been confirmed by several meta-analyses, small studies have not been included into these pooled analyses.AimPublication of recent RCTs prompted us to perform this updated meta-analysis to examine the consistency of favorable cardiovascular outcomes of SGLT2 inhibitors in HF patients by inclusion of clinical trials with small sample size.MethodsWe conducted a systematic review of the literature in PubMed/Medline and ClinicalTrials.gov to identify all RCTs investigating the benefits of SGLT2 inhibitors in patients with HF. The primary endpoint of this meta-analysis was to compare the cardiovascular death (CVD) and hospitalization for HF (HHF) between patients who received an SGLT2 inhibitor and those who received a placebo or a non-SGLT2 inhibitor. We used a risk difference (RD) and log hazard ratio (HR) to pool the reported difference across the included RCTs.ResultsA total of 12 RCTs encompassing 59,825 patients at different stages of HF and DM were included, 32,448 patients in the SGLT2 inhibitor group and 27,377 patients in the control group. A pooled analysis of RCTs, regardless of HF severity or DM status, showed a significantly reduced RD for CVD (RD =-0.01, 95% CI [-0.01, 0.00], P=0.01) and HHF (RD =-0.02, 95% CI [-0.03, -0.01], P=0.0005) in patients who received a SGLT2 inhibitor compared to those who did not. A sub-group analysis showed a significantly reduced RD for CVD (RD =-0.01, 95% CI [-0.02, 0.00], P=0.03) and HHF (RD =-0.02, 95% CI [-0.03, 0.00], P=0.01) in patients with DM who received SGLT2 inhibitors regardless of the severity of HF. Also, regardless of DM status, RD for HHF favored the use of SGLT2 inhibitor than the control medication (RD =-0.05, 95% CI [-0.06, -0.03], P<0.00001).ConclusionSGLT2 inhibitors have shown a promise in reducing CVD and HHF in patients with HF, regardless of ejection fraction or diabetes status.

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Benefits of SGLT2 inhibitors in arrhythmias.

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Benefits of SGLT2 inhibitors in arrhythmias.

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