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Association between Empagliflozin Use and Electrocardiographic Changes - PubMed

Association between Empagliflozin Use and Electrocardiographic Changes - PubMed

Source :

https://pubmed.ncbi.nlm.nih.gov/35892445/

Empagliflozin, a sodium-glucose transporter 2 inhibitor, has been shown to bind to late sodium channels in mice cardiomyocytes. We sought to investigate the electrocardiographic (ECG) features associated with empagliflozin use in patients with diabetes mellitus. We compared ECG features of 101 patie ...



Conclusion: We compared ECG features of 101 patients before and after initiation of empagliflozin and found that empagliflozin was associated with a significant increase in QRS duration among diabetes patients with heart failure.



  • August 02, 2022
    Key Points
    • Source: Clinics and Practice
    • Relevance: “Empagliflozin, a sodium-glucose transporter 2 inhibitor, has been shown to bind to late sodium channels in mice cardiomyocytes. We sought to investigate the electrocardiographic (ECG) features associated with empagliflozin use in patients with diabetes mellitus.”
    • The U.S. investigators compared ECG features of 101 patients (16 with diabetes plus heart failure) before and after taking empagliflozin and discovered that empagliflozin was correlated with an increase in QRS duration in patients with diabetes plus heart failure.
    • Regardless of diabetes status, the American College of Cardiology promotes the utilization of sodium-glucose cotransporter 2 (SGLT2) inhibitors including dapagliflozin and empagliflozin as adjunct therapy for heart failure with reduced ejection fraction (HFrEF). Empagliflozin reduces the chances of CV death or HF hospitalizations in individuals with HF with preserved or mid-range ejection fraction.
    • SGLT2 inhibitors also could have antiarrhythmic effects, such as a decrease in the odds of atrial fibrillation, atrial flutter, and new-onset arrhythmias. This effect could be because they change the comorbid risk factors for arrhythmia pathogenesis, although exact mechanisms need to be elucidated.
    • Pre-diabetes and diabetes mellitus are independently associated with the manifestation of atrial fibrillation and ventricular arrhythmias
    • Researchers noted an increase in the QRS duration in HF patients administered a 10 mg-empagliflozin dose from 109 ± 22 ms to 120 ± 24 ms. QRS prolongation could mediate ventricular desynchrony, thus impairing cardiac output and raising myocardial demand, as well as contributing to global decompensation of HF symptoms.
    • Longer QRS duration independently predicts all-cause mortality and sudden death. The 25 mg of dose of empagliflozin is indicated if increased glycemic control is desired. Suboptimal glucose control in the 10 mg group could have led to an increase in sodium channel subunit glycosylation.
    • “Protein subunit glycosylation can occur non-enzymatically, and the extent of glycosylation is directly proportional to the glucose concentration of the milieu in which the protein exists. In patients with DM, there is persistent excess glycosylation and attaining serum glucose targets may alter the extent glycosylation,” the authors write. “Heavy glycosylation may alter the docking domain and binding of Empa on the human cardiomyocyte late sodium channel as seen in other membrane proteins. Empa use was associated with an insignificant reduction in the ventricular. Owing to its diuresis effects, it is expected that Empa use would correspond with reflex tachycardia, but this may be curtailed by the sympathetic attenuation effects of Empa.”
    • Limitations of the current study include the smaller sample size, lack of monitoring of medication compliance and hemoglobin-A1C, exclusion of other SGLT2 inhibitors, and limited duration.