Evaluation Of The Effect Of SGLT-2 Inhibitors On Atrial Fibrillation Recurrence In Diabetic Patients

Evaluation Of The Effect Of SGLT-2 Inhibitors On Atrial Fibrillation Recurrence In Diabetic Patients | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 13 April 2025 V1 Latest version Share on Evaluation Of The Effect Of SGLT-2 Inhibitors On Atrial Fibrillation Recurrence In Diabetic Patients Authors : Mücahit YARAR , Hasan ARI 0000-0002-9681-2374 [email protected] , Selma ARI , Mehmet MELEK , and Tahsin BOZAT Authors Info & Affiliations https://doi.org/10.22541/au.174451874.48914433/v1 Published Expert Opinion on Pharmacotherapy Version of record Peer review timeline 200 views 168 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Background and Aim : The relationship between SGLT-2 (sodium glucose cotransporter-2) inhibitors and atrial fibrillation (AF) recurrence is under investigation. The aim of this study was to investigate the effect of SGLT-2 inhibitors on AF recurrence in patients diagnosed with diabetes mellitus (DM) who underwent Direct Current Cardioversion (DCCV) in our clinic. Method : Consecutive DCCV was performed until to achieve 120 patients in SR (60 DM patients who used SGLT-2 inhibitors and 60 DM patients who did not use SGLT-2 inhibitors). Patients defined as SGLT-2 inhibitor user group and control group. The two groups were monitored for AF recurrence on the first day, then at one, three, and six months after CV. Result : During the six-months follow-up period, AF recurrence developed in 24 (40%) patients in SGLT-2 inhibitor group and in 35 (58.3%) of the control group, p= 0.04. In univariate analysis, AF duration, SGLT-2 inhibitor, left atrium diameter, and TAPSE value were significant parameters in terms of AF recurrence. In multivariate analysis, AF duration OR: 4.98; 95% CI (2.39-10.38), p< 0,001 and non-use of SGLT-2 inhibitors OR: 0.35; 95% CI (0.13-0.90), were found to be independent predictors for AF recurrence. Conclusion : AF recurrence ratio is significantly lower in patients using SGLT-2 inhibitors, in six-month follow-up period. AF duration was positive and SGLT-2 inhibitor using was negative independent predictors, for AF recurrence in DM patients. jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Evaluation Of The Effect Of SGLT-2 Inhibitors On Atrial Fibrillation Recurrence In Diabetic Patients Running title: SGLT-2 inhibitor and Atrial Fibrillation Mücahit YARAR, MD (a) ; Hasan ARI Professor, MD (a) ; Selma ARI Associate Professor, MD (a) ; Mehmet MELEK Associate Professor, MD (a) ; Tahsin BOZAT Professor, MD (a) (a) Bursa Postgraduate Hospital, Department of Cardiology, Bursa, Turkey jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Corresponding Author: Dr. Hasan ARI Bursa Postgraduate Hospital Department of Cardiology, Bursa, Turkey E-mail: [email protected] , [email protected] . Tel: +90 2243605050 Fax: +90 2243605055 Conflict of interest The authors have no relevant conflicts of interest to disclose. Sources of Funding There were no external funding sources for this study. Data Availability Statement Data are available from the authors upon reasonable request. Ethical Approval The present study was approved by the Bursa Postgraduate Hospital Clinical Research Ethics Committee with the ethics number 2011-KAEK-25 2022/10-17 and was conducted in accordance with the principles of the Declaration of Helsinki. Abstract Background and Aim : The relationship between SGLT-2 (sodium glucose cotransporter-2) inhibitors and atrial fibrillation (AF) recurrence is under investigation. The aim of this study was to investigate the effect of SGLT-2 inhibitors on AF recurrence in patients diagnosed with diabetes mellitus (DM) who underwent Direct Current Cardioversion (DCCV) in our clinic. Method : Consecutive DCCV was performed until to achieve 120 patients in SR (60 DM patients who used SGLT-2 inhibitors and 60 DM patients who did not use SGLT-2 inhibitors). Patients defined as SGLT-2 inhibitor user group and control group. The two groups were monitored for AF recurrence on the first day, then at one, three, and six months after CV. Result : During the six-months follow-up period, AF recurrence developed in 24 (40%) patients in SGLT-2 inhibitor group and in 35 (58.3%) of the control group, p= 0.04. In univariate analysis, AF duration, SGLT-2 inhibitor, left atrium diameter, and TAPSE value were significant parameters in terms of AF recurrence. In multivariate analysis, AF duration OR: 4.98; 95% CI (2.39-10.38), p< 0,001 and non-use of SGLT-2 inhibitors OR: 0.35; 95% CI (0.13-0.90), were found to be independent predictors for AF recurrence. Conclusion : AF recurrence ratio is significantly lower in patients using SGLT-2 inhibitors, in six-month follow-up period. AF duration was positive and SGLT-2 inhibitor using was negative independent predictors, for AF recurrence in DM patients. Keywords: Diabetes mellitus, Atrial fibrillation, SGLT-2 inhibitor. INTRODUCTION: Atrial fibrillation (AF) is the most common supraventricular arrhythmia and is common in diabetic patients. SGLT-2 (sodium glucose cotransporter-2) inhibitors are used in the treatment of patients diagnosed with diabetes mellitus (DM) and are also recommended with Class I indication in patients with heart failure (HF) (1). There is also new evidence that SGLT-2 inhibitors may affect arrhythmia-related outcomes. Post-hoc analyses of major SGLT-2 inhibitor studies have revealed a reduced incidence of AF and atrial flutter (AFl) among patients treated with SGLT-2 inhibitors compared with placebo. In a meta-analysis of 31 studies involving more than 75,000 participants, SGLT-2 inhibitors were associated with a lower risk of AF compared to placebo (2). Recent publications have shown that SGLT-2 inhibitors reduce the risk of AF or AFl in patients with diabetes by 20% (3). It has also been shown that the risk of AF recurrence is lower with the use of SGLT-2 inhibitors in patients with diabetes after AF ablation (3). However, the effect of SGLT-2 inhibitors in reducing the AF recurrence rate after medical or electrical cardioversion is still unclear. The aim of this study was to examine the effect of SGLT-2 inhibitors on AF recurrence after electrical cardioversion (CV) in patients with DM and AF. METHOD: STUDY POPULATION The study was started with the protocol numbered 2011-KAEK-25 2022/10-17 of our Hospital Ethics Committee. Patients diagnosed with DM and AF who were planned to undergo electrical cardioversion were evaluated for suitability for the study. DCCV was performed to patients eligible for the study after the examination and premedication. Consecutive DCCV was performed until a total of 120 SR patients were achieved. Sixty patients who used SGLT-2 inhibitors and achieved SR with DCCV, and 60 patients who did not use SGLT-2 inhibitors and achieved SR with DCCV, were included in the study. While patients in the first group were using SGLT-2 inhibitors, patients in the second group received their standard treatment (control group). Study inclusion criteria; patients > 18 years and < 90 years, a patient diagnosed with DM who underwent electrical cardioversion due to AF and was restored to sinus rhythm. Study exclusion Criteria; patient who are not suitable for anticoagulant use, have thyroid dysfunction, glomerular filtration rate ≤ 25 ml/min/1.73 m², patients whose sinus rhythm cannot be achieved with electrical cardioversion, malignancy patients, patients with acute or chronic inflammatory disease, patients with peripheral artery disease, patients with pacemakers, patients with advanced valve stenosis or insufficiency, patients who have had coronary bypass surgery, patients with percutaneous or surgical bioprosthesis or metallic valve surgery. STUDY PROTOCOL The demographic characteristics of the patients and the information from physical examinations were recorded. EKG, TTE, TEE findings, left ventricle (LV) and right ventricle (RV) tissue Doppler values, LV strain value, TAPSE, systolic pulmonary arterial pressure (sPAP) values were calculated according to ASE criteria. Laboratory tests (complete blood count, biochemical tests, HbA1c value), CHA2DS2-VASc score, height, weight, BMI, oral antidiabetic use, insulin use were recorded. BMI = Body weight (kg) / (Height) (m)² was calculated. According to the Arterial Hypertension Guidelines; blood pressure measured in the office at least 2 times ≥ 140/90 mmHg, at home ≥ 135/85 mmHg, and 24-hour average blood pressure with an ambulatory device ≥ 130/80 mmHg or the use of antihypertensive medication is defined as hypertension. If blood glucose is ≥ 200 mg/dl or HbA1c ≥ 6.5 at any time of the day, or if antidiabetic medication is used, the presence of diabetes is defined. Those with ≥ 50% lesions in coronary arteries detected by coronary angiography are defined as CAD. Cardioversion protocol ; Anticoagulation with heparin was given by continuous intravenous infusion (17 U/kg) to all patients before cardioversion and its dose adjusted to an activated partial thromboplastin time (aPTT) of 1.5–2 times of normal. Amiodarone infusion started (5 mg/kg IV loading dose infused over 10 minutes, followed by 1mg/min IV for 6 hours, then 0.5 mg/min IV for 18 hours) to patients who did not have intracardiac thrombus on TTE and TEE studies. Transthoracic electrical cardioversion was performed with delivery of synchronized biphasic DC shocks of 150, 200, and 270 J in the intensive care unit, the patients were sedated with intravenous midazolam during the procedure. For the purpose of this study, cardioversion was considered successful if atrial P-waves were unmistakably identified 5 min after the shock. Patients achieving SR received appropriate anticoagulation (DOAC) was started for at least 4 weeks after the procedure. Patients received a total of 4 weeks treatment with oral amiodarone (2 weeks 600 mg/kg and the following 2 weeks 200 mg/kg). Patients were evaluated on the 1st day, 1st month, 3rd month and 6th month after the procedure by physical exam, ECG and however they were advised to come immediately if they had symptoms of palpitations or rhythm irregularity. If the patients had symptoms of palpitation and their ECG recordings were SR, we evaluated the patients with rhythm Holter monitoring. The primary outcome was achieved for the patient with AF recurrence. AF was diagnosed if there was a chaotic rhythm lasting ≥30 seconds on the single-lead ECG (6). Statistical analysis Statistical evaluation was performed using the SPSS (Statistical Package for the Social Sciences ver.23, SPSS Inc, Chicago, Illinois, USA) computer program. Numerical variables were expressed as mean ± standard deviation and categorical variables as percentages. When comparing average values between the groups, the Student’s t-test was used for variables with normal distribution and the Mann-Whitney U test for variables that did not have normal distribution. Categorical variables were compared using the Chi-square test or Fisher’s exact test. Univariate and multivariate Logistic Regression analysis was used to identify AF recurrence predictors. The relationship between the use of SGLT-2 inhibitors and AF recurrence was evaluated using Kaplan-Meier analysis. In all evaluations, a value of p < 0.05 was considered statistically significant. Results The demographic characteristics of 120 patients with DM and AF who presented at our clinic and had sinus rhythm restored with electrical CV, using and not using SGLT-2 inhibitors, are shown in Table 1. The SGLT-2 inhibitors group was determined to have statistically significantly higher values than the group not using SGLT-2 inhibitors for the following parameters: CHA 2 DS 2 -VASc score: 4.5±1.0 vs 3.9±1.2 (p=0.01), Coronary Artery Disease: 51.7% vs 33.3% (p=0.04), Sitagliptin use: 21.7% vs 8.3% (p=0.04), Gliclazide use: 38.3% vs 18.3% (p=0.01), and Insulin use: 30% vs 15% (p=0.04). The biochemical parameters of patients using and not using SGLT-2 inhibitors are summarized in Table 2. In those using SGLT-2 inhibitors group, the BUN value was significantly higher compared to those not using: 23.3±9.9 vs 19.4±6.8; p=0.03, while HbA1c (%): 8.0±1.6 vs 7.3±1.3; p=0.01 and Na: 137.0±2.8 vs 138.4±3.1; p=0.01 value was significantly lower. The EKG and TTE parameters of patients using and not using SGLT-2 inhibitors are summarized in Table 3. In those using SGLT-2 inhibitors, the baseline EF (%), 46.2±14.3 vs 51.6±11.1; p=0.02; baseline LV global strain (-%), 11.3±3.8 vs 12.9±3.3; p=0.01; day 1 LV global strain (-%) 12.8±3.7 vs 14.4±3.5; p=0.01 were significantly lower compared to those not using. Univariate and multivariate logistic regression analysis was performed to determine the predictors of AF recurrence in the study patients (Table 4). In univariate analysis, AF duration 5.66 (2.99-10.74), p<0.001, non using of SGLT-2 inhibitor 0.47 (0.23-0.98), p=0.04, LA baseline diameter 1.18 (1.08-1.29), p<0.001, TAPSE value 0.88 (0.78-0.98), p=0.02 were found to be significant. In multivariate analysis, AF duration 4.98 (2.39-10.38), p<0.001 and non using SGLT-2 inhibitor were significant predictors 0.35 (0.13-0.90), p=0.03 for AF recurrence. At the end of the six-month follow-up period; AF recurrence was detected in 24 (40%) patients in the SGLT-2 inhibitors group, and in 35 (58%) patients in the group noo using of SGLT-2 inhibitors (p=0.04), in terms of AF recurrence (figure 1). DISCUSSION In this study, we examined the effect of SGLT-2 inhibitors on AF recurrence at 6-month follow-up in patients with DM; i) AF recurrence was detected in 40% of patients using SGLT-2 inhibitors and in 58% of patients not using of SGLT-2 inhibitors, ii) SGLT-2 inhibitor use was an independent predictor reducing AF recurrence, iii) prolonged AF duration was an independent predictor of AF recurrence. Although SGLT-2 inhibitors were first used as oral antidiabetic agents, studies have shown that these drugs have positive effects on cardiovascular and renal functions. These positive effects on cardiovascular system have been evaluated in many studies. SGLT-2 inhibitors have now become the drugs recommended with a class I indication in cardiology guidelines for the treatment of heart failure patients (1). The positive effects of SGLT2 inhibitors on the cardiovascular system can be listed as follows. These drugs inhibit glucose and sodium re-uptake in the kidney and reduce plasma volume, blood pressure, preload, afterload, vascular resistance and left ventricular wall stress (7). By causing glucosuria; SGLT-2 inhibitors decrease Hb A1c values, total fat mass (weight) and uric acid values (7). These effects we have listed, result in positive effects on cardiac contractility and diastolic functions. When the mechanisms of AF are examined, the main causes of AF development are electrical and mechanical remodeling. SGLT-2 inhibitors reduce LA pressure and LA wall stress by reducing plasma volume, blood pressure, and left ventricular wall stress. This may prevent the development of AF by preventing mechanical remodeling of the LA. Especially in heart failure patients, Ca +2 overload in myocardial cells constitutes the electrical mechanism that causes the development of AF (6). With the natriuresis and glucosuria provided by SGLT-2 inhibitors, this Ca +2 overload will be reduced in heart failure patients and therefore the development of AF will also be reduced. High glucose levels may cause atrial autonomic neuropathy, changes in atrial excitation-contraction threshold, and myocyte inflammation, leading to the development of AF (6). SGLT-2 inhibitors may also prevent the development of AF by providing glycemic control in diabetic patients. Previous studies have shown that increased BMI values are associated with AF recurrence (6). SGLT-2 inhibitors may prevent the occurrence of AF recurrence by causing weight loss in patients. The development of AF is less common in patients using SGLT-2 inhibitors, as shown in meta-analyses of large studies (8, 9, 10, 11). These studies have shown that the use of SGLT-2 inhibitors provides an approximately 30% relative risk reduction in terms of the development of AF (9, 10, 12). In a study conducted with patients who used SGLT-2 inhibitors and underwent AF ablation, the use of SGLT-2 inhibitors was reported to reduce AF recurrence (13,14). In a study in which patients who underwent AF ablation were followed up for 1 year, the use of SGLT-2 inhibitors provided a 15% relative risk reduction in terms of AF recurrence (13). The current study patients using SGLT-2 inhibitors had higher CHA 2 DS 2 -VASc scores, higher coronary artery disease, higher Hb A1c values, and higher insulin use rates, and the EF values and LV global strain values of the SGLT-2 inhibitor group were lower. Although the patient group using SGLT-2 inhibitors in this study consisted of higher-risk patients, the lower rate of AF recurrence in this patient group suggests that the positive effect of these drugs on AF recurrence would be greater in the lower-risk group. Atrial contribution in heart failure patients may improve their symptoms and reduce their hospitalizations. Preventing AF recurrence may also prevent embolic complications, that may develop in this patient group. Compared with patients presenting with newly diagnosed AF, patients with longer duration of AF exposure have increased deterioration in LA and LV function. Long-term exposure to AF also causes mechanical, electrical and structural changes in the LA. LA structural remodeling due to long-term AF increases the risk of AF recurrence in these patients. In the current study, AF duration was found to be an independent predictor of AF recurrence (15,16). Many previous studies, such as ours, have also shown that AF duration is a predictor of AF recurrence (9, 10, 12, 17, 18). In the univariate analysis, we found that in addition to these two parameters (SGLT-2 inhibitor use, AF duration), LA diameter and TAPSE values were significant variables in terms of AF recurrence. LA diameter may be an indicator of remodeling and impaired LV systolic and/or diastolic dysfunction. As we know, increased left atrial fibrosis in patients with large LA diameter increases the recurrence of AF and makes it difficult to achieve sinus rhythm after CV in these patients (15,16,17,18). The association of decreased TAPSE values with AF recurrence suggests that right ventricular dysfunction may cause AF recurrence, particularly by causing right atrial and ventricular remodeling. Again, worsening right ventricular function may cause AF recurrence by reducing left ventricular filling and affecting left ventricular diastolic function. The limitations of this study can be said to be the single-centre design, that it was not randomised, the number of patients was limited and only diabetic patients were included with a six-month evaluation period. Nevertheless, this study is the first study in the literature to have evaluate AF recurrence after CV in patients using SGLT-2 inhibitors. Thus it can be considered that it will be of pioneer for further new studies to be conducted. Conclusion The results of this study demonstrated that the risk of AF recurrence decreased with the use of SGLT-2 inhibitors after electrical CV in diabetic patients. In this patient group, non-use of SGLT-2 inhibitor and prolonged AF duration were found to be independent predictors of AF recurrence. There is a need for further, randomized, controlled trials with long-term follow-up of larger patient groups to investigate the effects of SGLT-2 inhibitors on AF recurrence in patients with and without diabetes to be able to make further contributions to the literature about SGLT-2 inhibitors used to maintain SR. This study will pioneer for the further trials. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Mücahit YARAR, Hasan ARI, Mehmet MELEK, and Selma ARI. The first draft of the manuscript was written by Mücahit YARAR, Hasan ARI, Mehmet MELEK, Selma ARI and Tahsin BOZAT and all authors commented on this versions of the manuscript. All authors read and approved the final manuscript. Ethical Approval The present study was approved by the Bursa Postgraduate Hospital Clinical Research Ethics Committee and was conducted in accordance with the principles of the Declaration of Helsinki. Availability of data and material The data from this study will be shared if requested. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent for publication The authors affirm that human research participants provided informed consent for publication of the article. All authors consent to publication for this article. References : 1. 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Efficacy of sodium-glucose cotransporter 2 inhibitors on outcomes after catheter ablation for atrial fibrillation. Clinical Electrophysiology. 2022;8(11):1393-404. 14. Abu-Qaoud MR, Kumar A, Tarun T, Abraham S, Ahmad J, Khadke S, Husami R, Kulbak G, Sahoo S, Januzzi JL Jr, Neilan TG, Baron SJ, Martin D, Nohria A, Reynolds MR, Kosiborod M, Dani SS, Ganatra S. Impact of SGLT2 Inhibitors on AF Recurrence After Catheter Ablation in Patients With Type 2 Diabetes. JACC Clin Electrophysiol. 2023 Oct;9(10):2109-2118. doi: 10.1016/j.jacep.2023.06.008. 15. Çamcı S, Arı H, Arı S, Melek M, Bozat T. The Predictive Value of the Left Atrial Kinetic Energy for Atrial Fibrillation Recurrence. Cureus. 2022 Sep 3;14(9):e28714. doi: 10.7759/cureus.28714. 16. Ari H, Ari S, Akkaya M, Aydin C, Emlek N, Sarigül OY, Çetinkaya S, Bozat T, Şentürk M, Karaağaç K, Melek M, Yilmaz M. Predictive value of atrial electromechanical delay for atrial fibrillation recurrence. Cardiol J. 2013;20(6):639-47. doi: 10.5603/CJ.2013.0164. 17. Corradi D, Callegari S, Maestri R, Benussi S, Alfieri O. Structural remodeling in atrial fibrillation. Nature clinical practice Cardiovascular medicine. 2008;5(12):782-96. 18. Frick M, Frykman V, Jensen‐Urstad M, Östergren J. Factors predicting success rate and recurrence of atrial fibrillation after first electrical cardioversion in patients with persistent atrial fibrillation. Clinical cardiology. 2001;24(3):238-44. Table 1. Demographic characteristics of the patients SGLT-2 inhibitor users and non-users Variable SGLT-2 inhibitor user (n=60) SGLT-2 inhibitor non-user (n=60) P Value Age, (year) 68,9±7,9 67,7±7,3 0,40 Gender, Male n (%) Female n (%) 25(%41,7) 35(%58,3) 23(%38,3) 37(%61,7) 0,70 Smoking, n (%) 26(%43,3) 22(%36,7) 0,45 BMI (kg/m 2 ) 30,5±6,5 30,7±5,1 0,79 CHA 2 DS 2 -VASc score 4,5±1,0 3,9±1,2 0,01 SBP (mmHg) 130,3±15,0 132,1±18,8 0,40 DBP (mmHg) 81,2±8,3 80,7±11,1 0,14 Heart rate (bpm) 74,7±7,8 75,7±7,8 0,53 Hypertension, n (%) 54(%90) 51(%85) 0,40 Hyperlipidemia, n (%) 49(%81,7) 45(%75) 0,37 Coronery Artery Disease, n, (%) 31(%51,7) 20(%33,3) 0,04 Antiaggregant, n (%) 25(%41,7) 21(%35) 0,45 Beta blocker, n (%) 56(%93,3) 53(%88,3) 0,34 ACEI/ARB, n (%) 52(%86,7) 46(%76,7) 0,15 MRA, n (%) 28(%46,7) 25(%41,7) 0,58 Metformin, n (%) 52(%86,7) 48(%80) 0,32 Vildagliptin, n (%) 13(%21,7) 10(%16,7) 0,48 Linagliptin, n (%) 7(%11,7) 3(%5) 0,18 Sitagliptin, n (%) 13(%21,7) 5(%8,3) 0,04 Gliklazid, n (%) 23(%38,3) 11(%18,3) 0,01 İnsülin, n (%) 18(%30) 9(%15) 0,04 AF duration, (month) 1,8±0,8 2,0±1,1 0,35 BMI: Body mass index, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, BPM: Beat per minute, ACEI: Angiotensin converting enzyme inhibitors, ARB: Angiotensin receptor blocker, MRA: Mineralocorticoid Receptor Antagonist, AF: Atrial Fibrillation Table 2. Biochemical characteristics of the patients SGLT-2 inhibitor users and non-users Variable SGLT-2 inhibitor user (n=60) SGLT-2 inhibitor non-user (n=60) P Value WBC (1000/μL) 8,3±3,3 7,5±2,3 0,15 Hg (g/dl) 12,3±2,2 12,6±1,7 0,40 BUN (mg/dl) 23,3±9,9 19,4±6,8 0,03 Creatinine (mg/dl) 1,05±0,3 1,0±0,3 0,42 GFR (ml/dk) 65,7±20,8 69,5±20,7 0,32 Total Cholesterol (mg/dl) 176,1±49,0 181,9±50,3 0,53 LDL (mg/dl) 93,0±35,7 104,0±43,2 0,13 Tg (mg/dl) 165,3±109,6 171,0±105,9 0,77 Na (mmol/L) 137,0±2,8 138,4±3,1 0,01 K (mmol/L) 4,4±0,4 4,4±0,5 0,59 AST (U/L) 20,9±8,2 23,0±12,5 0,28 ALT (U/L) 21,9±13,7 22,8±19,6 0,76 Total bilirubin (mg/dl) 0,65±0,31 0,69±0,30 0,50 Total protein (g/L) 70,4±6,8 68,0±8,1 0,08 Albumin (g/L) 40,8±5,2 40,7±5,7 0,96 Ferritin (ng/ml) 75,0±84,2 95,2±91,4 0,21 TSH (uIU/ml) 1,6±1,3 1,2±1,0 0,17 FT4 (ng/dl) 1,1±0,2 1,1±0,2 0,49 FT3 (pg/ml) 2,6±0,4 2,6±0,4 0,31 HbA1c (%) 8,0±1,6 7,3±1,3 0,01 BNP (pg/ml) 297,7±369,9 242,2±236,9 0,64 WBC: White blood cell, Hg: Hemoglobin, BUN: Blood Urea Nitrogen, GFR: Glomerular Filtration Rate, LDL: Low Density Lipoprotein, TG: Triglyceride, Na: Sodium, K: Potassium, AST: Aspartate transferase, ALT: Alanine aminotransferase, TSH: Thyroid stimulating hormone, FT4: Free T4, FT3: Free T3, HbA1c: Hemoglobin A1c, BNP: Brain Natriuretic Peptide Table 3. Electrocardiographic and Transthoracic echocardiographic parameters of the patients SGLT-2 inhibitor users and non-users Variable SGLT-2 inhibitor user (n=60) SGLT-2 inhibitor non-user (n=60) P Value Basal EF (%) 46,2±14,3 51,6±11,1 0,02 Basal LA diameter (mm) 44,2±4,2 44,0±5,2 0,76 Basal sPAP (mmHg) 36,3±11,1 36,7±11,0 0,83 Basal TAPSE (mm) 18,3±3,8 18,5±3,0 0,75 Basal Lateral TD S (cm/s) 8,0±2,5 8,1±2,0 0,84 Basal Lateral TD E (cm/s) 10,4±2,8 9,9±2,3 0,29 Basal Medial TD S (cm/s) 7,1±2,1 7,1±2,2 0,93 Basal Medial TD E (cm/s) 8,5±2,2 9,1±3,1 0,26 Basal RV TD S (cm/s) 16,0±4,8 16,0±4,4 0,95 Basal RV TD E (cm/s) 17,6±4,9 19,2±5,1 0,08 Basal LV Global strain (-%) 11,3±3,8 12,9±3,3 0,01 1. day sPAP (mmHg) 35,0±10,5 34,8±10,5 0,93 1.day TAPSE (mm) 19,7±4,0 19,7±3,5 0,98 1. day Lateral TD S (cm/s) 8,1±2,5 8,2±2,0 0,84 1. day Lateral TD E (cm/s) 10,0±2,2 10,3±2,1 0,56 1.day Lateral TD A (cm/s) 7,7±3,9 7,7±3,5 0,92 1.day Medial TD S (cm/s) 7,3±2,2 7,5±2,0 0,58 1.day Medial TD E (cm/s) 9,0±2,2 9,2±2,2 0,65 1.day Medial TD A (cm/s) 6,5±3,2 6,9±3,0 0,51 1.day RV TD S (cm/s) 15,5±3,9 16,3±4,0 0,30 1.day RV TD E (cm/s) 17,1±5,1 18,7±5,1 0,09 1.day RV TD A (cm/s) 14,4±6,0 14,7±5,3 0,77 1.day LV Global strain (-%) 12,8±3,7 14,4±3,5 0,01 1.day (E/(E’×S’) ratio) (s/cm) 1,72±0,96 1,79±0,74 0,65 1.day P vawe time (msn) 90,0±19,3 96,5±18,8 0,06 1.day QRS time (msn) 87,1±13,1 90,2±19,2 0,29 1.day PR time (msn) 159,2±26,3 167,6±33,9 0,13 1.day QTc time (msn) 442,4±38,3 446,4±30,2 0,52 EF : Ejection Fraction, LA : Left Atrium, sPAP :Systolic pulmonary artery pressure, TAPSE : Tricuspid annular plane systolic excursion, TDI : Tissue Doppler, LV: Left ventricle, RV: Right ventricle Table 4. Univariate and Multivariate Logistic Regression Analysis for Atrial Fibrillation Recurrence Predictors Variable Univariate Analysis P value Multivariate Analysis P value Age 1,02(0,98-1,07) 0,23 Gender 0,92(0,44-1,91) 0,82 Hypertension 0,82(0,27-2,44) 0,73 CHA 2 DS 2 -VASc score 1,01(0,75-1,36) 0,90 EF basal 0,98(0,96-1,01) 0,35 AF duration 5,66(2,99-10,74) <0,001 4,98(2,39-10,38) <0,001 SGLT-2 inhibitor using 0,47(0,23-0,98) 0,04 0,35(0,13-0,90) 0,03 LA diameter 1,18(1,08-1,29) <0,001 1,05(0,94-1,18) 0,34 TAPSE 0,88(0,78-0,98) 0,02 0,92(0,79-1,06) 0,28 LV Global Strain 0,93(0,85-1,03) 0,21 BNP 1,00(1,00-1,02) 0,11 Hg 1,07(0,89-1,28) 0,43 P vawe duration 0,99(0,97-1,01) 0,68 HbA1c 0,88(0,69-1,12) 0,31 EF : Ejection Fraction, LA : Left Atrium, TAPSE : Tricuspid annular plane systolic excursion, LV: Left ventricle, BNP: Brain Natriuretic Peptide, Hg: Hemoglobin, HbA1c: Hemoglobin A1c Figure Legends Figure 1. Kaplan-Meier Analysis of Atrial Fibrillation Recurrence with SGLT-2 inhibitor users and non-users Information & Authors Information Version history V1 Version 1 13 April 2025 Peer review timeline Published Expert Opinion on Pharmacotherapy Version of Record 3 Jul 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Mücahit YARAR Bursa Postgraduate Hospital View all articles by this author Hasan ARI 0000-0002-9681-2374 [email protected] Bursa Postgraduate Hospital View all articles by this author Selma ARI Bursa Postgraduate Hospital View all articles by this author Mehmet MELEK Bursa Postgraduate Hospital View all articles by this author Tahsin BOZAT Bursa Postgraduate Hospital View all articles by this author Metrics & Citations Metrics Article Usage 200 views 168 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Mücahit YARAR, Hasan ARI, Selma ARI, et al. Evaluation Of The Effect Of SGLT-2 Inhibitors On Atrial Fibrillation Recurrence In Diabetic Patients. Authorea . 13 April 2025. DOI: https://doi.org/10.22541/au.174451874.48914433/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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