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.

Heart failure (HF) with mid-range or mildly reduced ejection fraction (HFmrEF) is a separate clinical entity in the HF spectrum, with a left ventricular ejection fraction ranging from 40 to 49%. While sodium glucose co-transporter 2 inhibitors have become the cornerstone therapy for the entire HF spectrum, there are a few clinical trials of HFmrEF. This prospective observational study was conducted at Dubrava University Hospital, Zagreb, Croatia, from May 2021 to October 2023. We recruited 137 participants diagnosed with HFmrEF at admission. The majority were male, with a median age of 72 and overweight. A total of 110 participants were followed for 6 months and LVEF remained the same in the majority of patients (n = 62, 56.4%), improved in 32 patients (29.1%), and decreased in 3 patients (2.73%). A total of 64 participants were followed for 12 months: 39 remained the same (60.94%) and 25 improved. There were 13 deaths in (9.5%). While the empagliflozin group had a lower BMI at 6-month- and lower HbA1c at 12-month follow-up, there were no differences in death, HF hospitalizations, ER visits, or urinary tract infections in between groups. Despite recent and daily advances in the treatment of all HF phenotypes, HFmrEF still represents a challenge in everyday clinical practice.

Background: SGLT2 inhibitors improve outcomes in heart failure with reduced ejection fraction (HFrEF), but whether early recovery patterns after initiation differ according to HF etiology in real-world practice remains uncertain. Objective: To evaluate whether ischemic versus non-ischemic etiology is associated with different 6-month cardiac, renal, biomarker, and exploratory metabolic trajectories after early in-hospital SGLT2 inhibitor initiation in HFrEF. Materials and Methods: In this prospective single-center observational cohort (2022–2025), consecutive adults hospitalized with first-presentation acute HFrEF who initiated empagliflozin or dapagliflozin within 48 h of admission were enrolled. Patients were classified as having ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM). The primary analytic cohort included patients with paired baseline and 6-month echocardiography. The primary outcome was change in left ventricular ejection fraction (LVEF); eGFR and NT-proBNP were secondary outcomes. Exploratory metabolic/laboratory variables were summarized descriptively using paired available-case follow-up. The study was approved by the institutional ethics committee and registered in ClinicalTrials.gov under the CaRD registry framework (NCT06090591). Results: The paired 6-month echocardiographic analytic cohort comprised 241 patients who survived to reassessment (ICM n = 90; NICM n = 151). NICM showed greater improvement in LVEF than ICM (ΔLVEF +10% [IQR 0–18] vs. +5% [IQR 0–12]; p = 0.049) and a more favorable eGFR trajectory (ΔeGFR 0.30 [IQR −5.90 to 6.60] vs. −2.70 [IQR −12.60 to 3.40] mL/min/1.73 m²; p = 0.038). NT-proBNP declined substantially in both groups, with no between-group difference in change magnitude (p = 0.845), although 6-month values remained higher in ICM (p = 0.034). However, after multivariable adjustment, ischemic etiology was no longer independently associated with 6-month LVEF or eGFR outcomes. Exploratory metabolic findings varied descriptively by etiology but should be interpreted cautiously because follow-up completeness and background treatment intensity varied across variables. Conclusions: In this real-world cohort of patients with HFrEF who initiated SGLT2 inhibitors during hospitalization, HF etiology was associated with different short-term cardiorenal recovery patterns, whereas NT-proBNP reduction was similar across groups. These findings characterize etiology-related recovery within a treated cohort rather than differential SGLT2 inhibitor efficacy and should therefore be considered as hypothesis-generating.