The effect of SGLT2 inhibitors on cardio-electrophysiological balance index in diabetic patients with preserved ejection heart failure

Year 2023, Volume: 4 Issue: 3, 192 - 197, 27.09.2023

Gökhan Gökalp , Nail Burak Özbeyaz

https://doi.org/10.47482/acmr.1346676

Abstract

Background: Type 2 diabetes mellitus (DM) increases the risk of heart failure with preserved ejection fraction (HFpEF). The use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors, which have been shown to have cardioprotective effects in HFpEF, has increased in frequency. The index of cardio-electrophysiological balance (iCEB) is a marker that can be calculated on electrocardiography (ECG) and has been proven to be a good predictor of ventricular arrhythmia. This study aimed to investigate the effects of SGLT-2 inhibitors on iCEB and iCEBc in type 2 DM patients with HFpEF.
Methods: We retrospectively analyzed the data of 76 patients with type 2 DM with HFpEF who were started on SGLT-2 inhibitors. We compared the ECG parameters obtained at baseline and six-month follow-up.
Results: The mean age of the patients included in the study was 64.7±8.9 years. When ECG parameters before and after treatment were compared, iCEB (4.33±1.95 vs. 4.24±1.50, p= 0.006) and iCEBc (4.67±1.35 vs. 4.59±1.36, p<0.001) values were found to be decreased compared to before treatment.
Conclusion: The iCEB and iCEBc values of the patients decreased significantly after SGLT-2 inhibitors. These results suggest that SGLT-2 inhibitors may reduce the risk of ventricular arrhythmia in patients with HFpEF.

Keywords

diabetes mellitus, index of cardiac electrophysiological balance, sodium-glucose co-transporter-2 inhibitors, preserved ejection fraction heart failure.

References

• Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-81.
• Triposkiadis F, Xanthopoulos A, Bargiota A, Kitai T, Katsiki N, Farmakis D, et al. Diabetes mellitus and heart failure. J Clin Med. 2021;10(16):3682.
• Gulsin GS, Athithan L, McCann GP. Diabetic cardiomyopathy: prevalence, determinants and potential treatments. Ther Adv Endocrinol Metab. 2019;10:2042018819834869.
• McHugh K, DeVore AD, Wu J, Matsouaka RA, Fonarow GC, Heidenreich PA, et al. Heart failure with preserved ejection fraction and diabetes: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(5):602-11.
• Lehrke M, Marx N. Diabetes Mellitus and Heart Failure. Am J Med. 2017;130(6S):40-50
• Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323.
• Abudureyimu M, Luo X, Wang X, Sowers JR, Wang W, Ge J, et al. Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics. J Mol Cell Biol. 2022;14(5):1-12.
• Patel N, Ju C, Macon C, Thadani U, Schulte PJ, Hernandez AF, et al. Temporal trends of digoxin use in patients hospitalized with heart failure: Analysis from the American heart association get with the guidelines-heart failure registry. JACC Heart Fail. 2016;4(5):348-56.
• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-726.
• Paulus WJ, Dal Canto E. Distinct myocardial targets for diabetes therapy in heart failure with preserved or reduced ejection fraction. JACC Heart Fail. 2018;6(1):1-7.
• Zheng J, Parizo JT, Spertus JA, Heidenreich PA, Sandhu AT. Costeffectiveness of empagliflozin in patients with heart failure with preserved ejection fraction. JAMA Intern Med. 2022;182(12):1278-88.
• Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-61.
• Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-98.
• Pabel S, Wagner S, Bollenberg H, Bengel P, Kovács Á, Schach C, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur J Heart Fail. 2018;20(12):1690-700.
• Verma S, Rawat S, Ho KL, Wagg CS, Zhang L, Teoh H, et al. Empagliflozin increases cardiac energy production in diabetes: Novel translational insights into the heart failure benefits of SGLT2 inhibitors. JACC Basic Transl Sci. 2018;3(5):575-87.
• Lee TI, Chen YC, Lin YK, Chung CC, Lu YY, Kao YH, et al. Empagliflozin attenuates myocardial sodium and calcium dysregulation and reverses cardiac remodeling in Streptozotocin-induced diabetic rats. Int J Mol Sci. 2019;20(7):1680.
• Cho JH. Sudden Death and ventricular arrhythmias in heart failure with preserved ejection fraction. Korean Circ J. 2022;52(4):251-64.
• Locati ET, Bagliani G, Padeletti L. Normal ventricular repolarization and QT interval: Ionic background, modifiers, and measurements. Card Electrophysiol Clin. 2017;9(3):487-513.
• Antzelevitch C, Sicouri S, Di Diego JM, Burashnikov A, Viskin S, Shimizu W, et al. Does Tpeak-Tend provide an index of transmural dispersion of repolarization? Heart Rhythm. 2007;4(8):1114-6; author reply 1116-9.
• Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.
• Lu HR, Yan GX, Gallacher DJ. A new biomarker--index of cardiac electrophysiological balance (iCEB)--plays an important role in druginduced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs). J Pharmacol Toxicol Methods. 2013;68(2):250-59.
• Robyns T, Lu HR, Gallacher DJ, Garweg C, Ector J, Willems R, et al. Evaluation of index of cardio-electrophysiological balance (iCEB) as a new biomarker for the identification of patients at increased arrhythmic risk. Ann Noninvasive Electrocardiol. 2016;21(3):294-304.
• Castro Hevia J, Antzelevitch C, Tornés Bárzaga F, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina R, et al. Tpeak-Tend and Tpeak- Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol. 2006;47(9):1828-34.
• Balkau B, Jouven X, Ducimetière P, Eschwège E. Diabetes as a risk factor for sudden death. Lancet. 1999;354(9194):1968-9.
• İnci Ü, Güzel T. The effect of empagliflozin on index of cardioelectrophysiological balance in patients with diabetes mellitus. Pacing Clin Electrophysiol. 2023;46(1):44-49.
• Locati ET, Bagliani G, and Padeletti L. Normal ventricular repolarization and QT interval: Ionic background, modifiers, and measurements. Card Electrophysiol Clin. 2017;9(3):487-513.
• Ünal S, Yayla Ç, Açar B, Ertem AG, Akboğa MK, Gökaslan S, et al. Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus. J Infect Public Health. 2018;11(1):35-8.
• Sato T, Miki T, Ohnishi H, Yamashita T, Takada A, Yano T, et al. Effect of sodium-glucose co-transporter-2 inhibitors on impaired ventricular repolarization in people with Type 2 diabetes. Diabet Med. 2017;34(10):1367-71.
• Duran M, Ziyrek M, Alsancak Y. Effects of SGLT2 Inhibitors as an addon therapy to metformin on electrocardiographic indices of ventricular repolarization. Acta Cardiol Sin. 2020;36(6):626-32.
• Panikkath R, Reinier K, Uy-Evanado A, Teodorescu C, Hattenhauer J, Mariani R, et al. Prolonged Tpeak-to-tend interval on the resting ECG is associated with increased risk of sudden cardiac death. Circ Arrhythm Electrophysiol. 2011;4(4):441-7.
• Matthews VB, Elliot RH, Rudnicka C, Hricova J, Herat L, Schlaich MP. Role of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2. J Hypertens. 2017;35(10):2059-2068.