The effect of SLGT2 inhibitors on serum electrolyte levels, kidney function and NT-proBNP in patients with heart failure with preserved and reduced ejection fraction
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, p<.001). There were no differences in NTproBNP levels at 6 and 12 months between HFrEF and HFpEF groups (Table 1). There were no differences in eGFR or electrolytes serum levels at admission nor in the follow up (Table 2). NTproBNP levels decreased during the 6 and 12 months follow up, respectively (2264 vs 913.5pg/L, p<.0001 and 865 vs 681pg/L, p<.0001), while haematocrit levels increased (0.409 vs 0.424, p<.0001 and 0.4295 vs 0.431, p=.0001). The eGFR remained stable throughout the follow up period (66.45 vs 65.5mL/min/1.73m2, p=.0996 and 66 vs 65.5mL/min/1.73m2, 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) | <0.0001 |
| NT-proBNP at 6 months (pg/L) | 712 (610.27-1085.1) | 938 (862.73-1001.57) | 0.0981 |
| NT-proBNP at 12 months(pg/L) | 590 (420.94-939.67) | 689 (639.71-757.59) | 0.6358 |
| eGFR at admission (45mL/min/1.73m2) | 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, p<0.0001
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 |
TABLE 2 Comparison of NT-proBNP, hematocrit, kidney function and serum electrolyte levels in patients with heart failure with preserved and reduced ejection fraction.
| HFpEF group |
|---|
| C (95% Confidence interval) | P-value* |
| NT-proBNP at admission vs 6 months (pg/L) | 1439.5 (989.023-2055.28) vs 741 (615.6-1100-58) | 0.0001 |
| NT-proBNP at 6 months vs 12 months (pg/L) | 867 (603.32-1214.35) vs 599 (431.62-961.9) | 0.4595 |
| eGFR at admission vs 6 months ((45mL/min/1.73m2) | 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) | <0.0001 |
| eGFR at admission vs 6 months ((45mL/min/1.73m2) | 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.
