Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Serum Chloride Concentrations in Patients with Heart Failure

Background and aims: In the past few years, some reports have shown that serum chloride concentration is a more powerful prognostic predictor than serum sodium levels in heart failure (HF). Elevated Na/Cl ratio has shown to be independently associated with all-cause death in acute HF. We evaluated changes in serum chloride concentrations and Na/Cl ratio in correlation with various clinical factors during 12 months of follow-up in patients in whom SGLT2is were initiated as part of HF therapy. Patients and methods: This was a prospective observational study conducted at University Hospital Dubrava and involving patients with HF. We included 241 participants between May 2021 and April 2023. All data were obtained before the introduction of SGLT2is, and the same parameters were obtained at 6 and 12 months of follow-up as well. Results: The results show that higher chloride concentration at both 6 and 12 months is an independent predictor of lower NT-proBNP levels. The chloride concentrations did not differ significantly between these groups in the follow-up period. There were no statistically significant differences in the Na/Cl ratio at different timepoints. The presence of cardiovascular risk factors did not significantly affect the increase in chloride concentration. Conclusions: Our results suggest that hypochloremia could be a potentially modifiable risk factor, given the influence of SGLT2is on chloride concentration, but also an ominous sign of a poor outcome in patients with HF. We believe that the determination of chloride concentrations should become routine in the monitoring of patients with HF.