Authors

• Marin Viđak — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0003-0341-9598
• Petra Vitlov — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-6983-1409
• Jasmina Ćatić — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-6582-4201
• Ana Jordan — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-5610-6259
• Andrej Novak — University of Zagreb, Faculty of Science, Zagreb, Croatia — ORCID: 0000-0002-7828-4870
• Vanja Ivanović Mihajlović — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-6931-5404
• Marin Pavlov — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0003-3962-2774
• Marta Puškadija — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0009-0004-1361-3911
• Nikola Pavlović — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-9187-7681
• Ivan Zeljković — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-4550-4056
• Šime Manola — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-6444-2674
• Ivana Jurin — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-2637-9691

Keywords

heart failure, sodium-glucose cotransporter 2 inhibitors, kidney function

DOI

Full Text

**Introduction**: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have become the cornerstone of heart failure (HF) therapy across the ejection fraction (EF) spectrum, with plethora of metabolic effects (1, 2). Knowledge on effects of SGLT2i on electrolyte levels and kidney function in patients with preserved (HFpEF) and reduced HF (HFrEF) is still limited. **Patients and Methods**: This was a registry-based study recruiting patients diagnosed with HF from May 2021 to February 2024 in Dubrava University Hospital, Zagreb, Croatia. We extracted data on age, gender, NTproBNP and electrolytes levels, and estimated glomerular filtration rate (eGFR). Patients with mildly reduced EF were grouped with patients with HFrEF. **Results**: We have collected data from 1018 patients diagnosed with HF (median age 70 (95%CI 69-70.76) years, 33% female). HFpEF was diagnosed in 125 (12.3%), while HFrEF was diagnosed in 893 (87.7%) patients. There were 69 women (55.2%) in the HFpEF group and 267 women (29.9%) in the HFrEF group. Patients were younger in the HFrEF group (69 vs 73 years, p=.0004). HFpEF group had higher BMI when compared to HFrEF group (30.44 vs 28.67, p=.0074). Initial NTproBNP was higher in the HFrEF group (1615.5 vs 2667pg/L, p2, p=.1453). ### TABLE 1: Participants’ characteristics (N=1018). | | **HFpEF group (N=125)** | **HFrEF group (N=893)** | **P-value*** | | --- | --- | --- | --- | | Age | 73 (72.0-74.94) | 69 (68-70) | **0.0004** | | Sex | | | | | Male | 56 (52.5%) | 626 (70.01%) | | | Female | 69 (47.5%) | 267 (29.9%**)#** | | | Body mass index (kg/m2) | 30.44 (28.92-31-37) | 28.67 (27.96-29.16) | **0.0074** | | NT-proBNP at admission (pg/L) | 1615.5 (1098.43-2020-84) | 2667 (2413.96-3083.03) | **2) | 65.09 (60.31-69.7) | 66 (63.89-67.85) | 0.4071 | | eGFR at 6 months (45mL/min/1.73m2) | 66.2 (49.96-73.85) | 65.4 (63-67.42) | 0.1707 | | eGFR at 12 months (45mL/min/1.73m2) | 63.1 (48.22-77.01) | 65.7 (61.23-68.8) | 0.2103 | | Potassium at admission (mmol/L) | 4.3 (4.2-4.4) | 4.3 (4.3-4.4) | 0.8729 | | Potassium at 6 months (mmol/L) | 4.3 (3.96-4.73) | 4.3 (4.3-4.4) | 0.6646 | | Potassium at 12 months (mmol/L) | 4.5 (4.2-4.61) | 4.4 (4.4-4.6) | 0.4323 | | Chloride at admission (mmol/L) | 103 (102-103) | 103 (102-103) | 0.8178 | | Chloride at 6 months (mmol/L) | 102 (101-103) | 103 (102-103) | 0.400 | | Chloride at 12 months (mmol/L) | 104 (103-104) | 103 (103-103) | 0.4078 | | Hematocrit at admission | 0.3975 (0.3907-0.4056) | 0.411 (0.407-0.415) | 0.1042 | | Hematocrit at 6 months | 0.4050 (0.3905-0.4239) | 0.426 (0.421-0.0431) | **0.0171** | | Hematocrit at 12 months | 0.4265 (0.4010-0.4430) | 0.4310 (0.4260-0.4377) | 0.3972 | [†] * Mann-Whitney test, # Chi square test, p2) | 67.06 (56.6-74.32) vs 66.2 (49.96-73.85) | **0.0375** | | eGFR at 6 months vs 12 months (45mL/min/1.73m2) | 62.8 (44.83-75) vs 59.2 (57.8-77.01) | 0.4595 | | Hct at admission vs 6 months | 0.3925 (0.3832-0.4066) vs 0.4045 (0.3901-4230) | 0.2007 | | Hct at 6 months vs 12 months | 0.419 (0.383-0.4354) vs 0.4265 (0.4010-0.4467) | **0.0431** | | Potassium level at admission vs 6 months (mmol/L) | 4.15 (4.0-4.372) vs 4.3 (3.964-4.7361) | 0.2293 | | Potassium level at 6 months vs 12 months (mmol/L) | 4.1 (3.95-4.45) vs 4.15 (3.95-4.6) | 0.375 | | Chloride level at admission vs 6 months (mmol/L) | 103 (100-104) vs 102 (101-103) | 0.4320 | | Chloride level at 6 months vs 12 months (mmol/L) | 103 (101.02-104.97) vs 103 (102-104) | 0.1055 | | **HFrEF group** | | | | | **C (95% Confidence interval)** | **P-value*** | | NT-proBNP at admission vs 6 months (pg/L) | 2416 (2032.58-2687.03) vs 938 (863.33-1001-42) | **0.0001** | | NT-proBNP at 6 months vs 12 months (pg/L) | 865 (765.9-966) vs 685 (637.53-755.56) | **2) | 66.34 (64.59-68.66) vs 65.4 (63-67.42) | 0.3025 | | eGFR at 6 months vs 12 months (45mL/min/1.73m2) | 66.1 (64.23-69.1) vs 65.6 (61.16-68.8) | **0.095** | | Hct at admission vs 6 months | 0.4110 (0.4070-0.4160) vs 4.260 (0.4210-0.4310) | **<0.0001** | | Hct at 6 months vs 12 months | 0.430 (0.422-0.433) vs 0.4310 (0.4259-0.4371) | **0.0005** | | Potassium level at admission vs 6 months (mmol/L) | 4.3 (4.2-4.3) vs 4.3 (4.3-4.4) | **0.0197** | | Potassium level at 6 months vs 12 months (mmol/L) | 4.3 (4.23-4.4) vs 4.4 (4.227-4.5) | 0.5033 | | Chloride level at admission vs 6 months (mmol/L) | 102 (99-104) vs 103 (100-104) | **0.0052** | | Chloride level at 6 months vs 12 months (mmol/L) | 103 (101-105) vs 103 (101-105) | 0.8231 | [†] * Wilcoxon paired sample test HFrEF = heart failure with reduced ejection fraction, HFpEF = heart failure with preserved ejection fraction, NT-proBNP = N-terminal prohormone of brain natriuretic peptide, eGFR = estimated glomerular filtration rate, Hct = hematocrit **Conclusions**: There were no differences in electrolyte levels and kidney function between HFpEF and HFrEF groups, confirming that SLGT2 inhibitors provide similar efficacy across the spectrum of HF patients.

Literature

1. Authors/Task Force Members, McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2024 January;26(1):5–17. https://doi.org/10.1002/ejhf.3024
2. Nashawi M, Sheikh O, Battisha A, Ghali A, Chilton R. Neural tone and cardio-renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus on SGLT2 inhibitors. Heart Fail Rev. 2021 May;26(3):643–52. https://doi.org/10.1007/s10741-020-10046-w