Impact of Serum Chloride and Sodium Levels on the Prognostic Effect of SGLT2 Inhibitors in Heart Failure: The QHEART Retrospective Cohort Study
K Misumi, T Hashimoto, G Taniguchi, T Yoshitake, K Ikuta, T Fujino, K Shinohara, S Matsushima, K Ishimaru, R Matsukawa, M Fujiwara, S Furusawa, A Ishikita, K AbeAbstract
Background
Decreased serum sodium (Na) and chloride (Cl) concentrations are each known independent predictors of poor prognosis in patients with heart failure (HF). However, their impact on the effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2i) and other guideline-directed HF medications remains unclear.
Purpose
This study aimed to evaluate whether the prognostic effects of SGLT2i and other major HF medications differ according to serum Na and Cl levels at discharge.
Methods
Quality of HEart Failure CARe and OuTcomes (QHEART) Registry Retrospective Cohort (QHEART-R) Study included patients hospitalized for worsening HF from October 2020 through December 2024 at six institutions in Japan. Low Na and Low Cl at discharge were defined as serum Na <135 mmol/L and Cl <97 mmol/L, respectively. Patients were stratified according to use of SGLT2i, β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and renin–angiotensin system (RAS) inhibitors (ACEi/ARB/ARNI) at discharge. The primary endpoint was a composite of all-cause death or HF rehospitalization within 3 months after discharge.
Results
A total of 2,613 patients were analyzed (mean age 77 years, 55% male, mean LVEF 44%). Low Na and low Cl were observed in 11% and 7% of patients, respectively. As shown in Figure1, both low Na and low Cl were associated with worse 3-month prognosis compared with normal Na or Cl values (Low Na: HR 1.75 [1.31–2.33], Low Cl: HR 1.91 [1.37–2.65]). SGLT2i use was associated with favorable outcomes in patients with normal Na and Cl (Normal Na: HR 0.52 [0.40-0.68], Normal Cl: HR 0.50 [0.39-0.65]), and also in low Na patients (HR 0.56 [0.31-0.98]), but no prognostic benefit was observed in low Cl patients (HR 0.92 [0.48-1.75]) (Figure 2). No significant differences in effect across Na or Cl strata were observed for BB, MRA, or RAS inhibitors.
Conclusions
In HF patients with low Cl at discharge, the prognostic benefit of SGLT2i may be attenuated. In contrast, BB, MRA, and RAS inhibitors showed no significant differences in effect across Na or Cl strata. These findings provide novel insights into the mechanisms of SGLT2i and guide drug selection in patients with electrolyte abnormalities.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.