Background: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. Methods: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. Results: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P <0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P <0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P <0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P =0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P =0.852). Conclusions: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.

Objective To determine the impact of sodium-dependent glucose type 2 cotransporter inhibitors on the renal function in acute heart failure. Methods In a single-centre, controlled, randomised study, patients were prescribed dapagliflozin in addition to standard therapy, or were in receipt of standard therapy. The prespecified outcome was renal function deterioration; the secondary outcomes were the development of resistance to diuretics, weight loss, death during hospitalisation and the rehospitalisation or death for any reason within 30 days following discharge. Results 102 patients were included (73.4±11.7 years, 57.8% men). The average left ventricular ejection fraction was 44.9%±14.7%, the average N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was 4706 (1757; 11 244) pg/mL, the average estimated glomerular filtration rate (eGFR) was 51.6±19.5 mL/min. eGFR decreased 48 hours after randomisation in the dapagliflozin group (−4.2 (−11.03; 2.28) mL/min vs 0.3 (−6; 6) mL/min; p=0.04) but did not differ between the groups on discharge (54.71±19.18 mL/min and 58.92±24.65 mL/min; p=0.36). The incidence of worsening renal function did not differ (34.4% vs 15.2%; p=0.07). In the dapagliflozin group, there was less tendency to increase the dose of loop diuretics (14% vs 30%; p=0.048), lower average doses of loop diuretics (78.46±38.95 mg/day vs 102.82±31.26 mg/day; p=0.001) and more significant weight loss (4100 (2950; 5750) g vs 3000 (1380; 4650) g; p=0.02). In-hospital mortality was 7.8% (4(8%) in the dapagliflozin and 4 (7.7%) in the control group (p=0.95). The number of deaths within 30 days following discharge in the dapagliflozin group and in the control group was 9 (19%) and 12 (25%), p=0.55; the number of rehospitalisations was 14 (29%) and 17 (35%), respectively (p=0.51). Conclusion The use of dapagliflozin was associated with a more pronounced weight loss and less need to increase diuretic therapy without significant deterioration of the renal function. Dapagliflozin did not improve the in-hospital and 30-day prognosis after discharge. Trial registration number N04778787.

Background: The venous excess ultrasound score (VExUS) is used to objectify systemic venous congestion. The aim of the paper was to determine the association between VExUS grades and worsening renal function (WRF), reduced natriuretic response, diuretics resistance, and mortality in patients with acute heart failure (AHF). Methods: One hundred patients were included, and Doppler ultrasound of hepatic, portal, and renal veins was performed. Severity of congestion was graded using the VExUS score (grade 0, 1, 2, or 3). Sodium concentration in a spot urine sample was assessed in 2 h after the first loop diuretic administration and was adjusted for the prescribed dose of furosemide (31 mmol/40 mg). Diuretics resistance was defined as the need to double the starting dose of intravenous furosemide in 6 h. Results: Patients with VExUS grade 3 showed a higher incidence of WRF (OR: 11.17; 95% CI: 3.86–32.29; p < 0.001) and a decreased natriuretic response: a spot urine sodium content of <50 mmol/L (OR: 21.53; 95% CI: 5.32–87.06; p < 0.001) and an adjusted spot urine sodium content of <31 mmol/40 mg (OR: 9.05; 95% CI: 3.15–25.96; p < 0.001). The risk of diuretic resistance (OR: 15.31; 95% CI: 5.05–46.43; p < 0.001), as well as the need for inotropic and/or vasopressor support (OR: 11.82; 95% CI: 3.59–38.92; p < 0.001), was higher in patients with severe congestion. The hospital mortality rate increased in patients with VExUS grade 3 compared to in patients with other grades (OR: 26.4; 95% CI: 5.29–131.55; p < 0.001). Conclusions: Patients with AHF and VExUS grade 3 showed a higher risk of developing WRF, a decreased diuretic and natriuretic response, a need for inotropic and/or vasopressor support, and a poor prognosis during their hospital stay.

Introduction: The dynamics of serum sodium are important in acute heart failure (AHF), and hyponatremia is associated with a poor prognosis. The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on serum sodium concentrations in AHF is unknown. Methods: In a single-centre, controlled, randomized study, patients were prescribed dapagliflozin in addition to standard treatment during the first 24 h of hospitalization versus standard treatments. The pre-specified outcome was an absolute change in plasma sodium concentrations between randomization (first 24 h after admission) and discharge. The secondary outcomes were an absolute change in serum sodium concentrations within 48 h of randomization and the persistence of hyponatremia. Results: The sample comprised 285 patients (53% males; average age 73.26 ± 13 years); 140 of these were randomized to the dapagliflozin group. The average ejection fraction was 46 ± 14%; 155 patients (54%) had ischaemic heart failure; and 35% had diabetes mellitus. Median N-terminal pro b-type natriuretic peptide was 4,225 [2,120; 9,105] pg/mL. The average estimated glomerular filtration rate was 53.9 ± 17.2 mL/min. Hospital mortality was 6.7%. At randomization, serum sodium concentrations were 139.8 ± 4.32 mmol/L in the dapagliflozin group versus 140.85 ± 4.04 mmol/L in the control group; p = 0.048. 48 h later, there was an increase in serum sodium in the dapagliflozin group (2 [−2; 4] mmol/L), as compared to the control group (−1 [−3.75; 2]); p < 0.001. This was accompanied by equilibration of the sodium levels between the groups (141.08 ± 4.08 mmol/L in the dapagliflozin group vs. 140.05 ± 4.82 mmol/L in the control group; p = 0.096). At the time of discharge, there was no difference in serum sodium concentrations (140.98 ± 4.77 mmol/L vs. 139.86 ± 4.45 mmol/L; p = 0.082). The increase in serum sodium concentrations during the period of observation [randomization; discharge] was small but statistically significant in the dapagliflozin group (1 [−3; 3.75] mmol/L vs. −2 [−4.5; 2] mmol/L; p = 0.015). Of 36 patients (21 in the dapagliflozin group and 15 in the control group) with baseline hyponatraemia, this persisted in 6 (16.6%) in the dapagliflozin group and in 11 (73.3%) in the control group (p = 0.008). Conclusion: The use of dapagliflozin in AHF is associated with a tendency to the increase in serum sodium concentrations and lesser persistence of hyponatremia. This effect occurred within the first 48 h and persisted until discharge. The impact of dapagliflozin on serum sodium was more pronounced in patients with hyponatremia at randomization.

Aim To determine the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney function in acute decompensated heart failure (ADHF). Material and methods A controlled randomized study on the dapagliflozin treatment in ADHF was performed. Patients were randomized to a main group (standard therapy supplemented with dapagliflozin) or a control group (standard therapy for ADHF). The primary endpoint was the development of acute kidney injury (AKI). 200 patients were included (mean age, 74±12 years; 51% men). 31% of patients had type 2 diabetes mellitus (DM2). Mean left ventricular ejection fraction (LV EF) was 47±14 %; in 44.5% of patients, LV EF was less than 45%. Median concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was 5225 [3120; 9743] pg / ml, glomerular filtration rate (GFR) was 51 [38; 64] ml / min / 1.73 m2. Results In-hospital mortality was 6.5%. Analysis of the dynamics of body weight loss showed significant differences (4200 [2925; 6300] g vs. 3000 [1113; 4850] g; p=0.011) in favor of the dapagliflozin group. The requirement for increasing the daily dose of furosemide and adding an another class diuretic (thiazide or acetazolamide) did not differ between the groups. However, median furosemide dose during the stay in the hospital was lower in the dapagliflozin group (80 [67; 120] mg vs. 102 [43; 120] mg; p=0.016). At 48 hours after randomization, GFR significantly decreased in the dapagliflozin group (–5.5 [–11; 3] ml/min/ 1.73 m2) compared to the control group (–0.3 [–4; 5] ml / min/1.73 m2, р=0.012). Despite this, GFR did not differ between the groups at discharge (51 [41; 66] ml/min/1.73 m2 and 49 [38; 67] ml/min/1.73 m2, respectively; p = 0.84). In the dapagliflozin group, frequency of AKI episodes was not increased compared to the control group (13 and 9.4%, respectively; p = 0.45). Conclusion The dapagliflozin treatment in ADHF is associated with more pronounced body weight loss and lower average doses of loop diuretics during the period of stay in the hospital, with no associated clinically significant impairment of renal function.

Background: Acute heart failure (AHF) is one of the leading causes of admissions to the emergency department (ED). There is a need to develop an easy-to-use score that can be used in the ED to risk-stratify patients with AHF and in hospitalization decisions regarding cardiac wards or intensive care units (ICUs). Methods: A retrospective observational study was conducted at a city hospital. The data from the presentation of AHF patients at the ED were collected. The combined primary endpoint included death from any cause during hospitalization or transfer to an intensive care unit (ICU) for using inotropes/vasopressors. Feature selection was performed using artificial intelligence. Results: From August 2020 to August 2021, 908 patients were enrolled (mean age: 71.6 ± 13 years; 500 (55.1%) men). We found significant predictors of in-hospital mortality and ICU transfers for inotrope/vasopressor use and built two models to assess the need for ICU admission of patients from the ED. The first model included SpO₂ < 90%, QTc duration, prior diabetes mellitus and HF diagnosis, serum chloride concentration, respiratory rate and atrial fibrillation on admission, blood urea nitrogen (BUN) levels, and any implanted devices. The second model included left ventricular end-diastolic size, systolic blood pressure, pulse blood pressure, BUN levels, right atrium size, serum chloride, sodium and uric acid concentrations, prior loop diuretic use, and pulmonary artery systolic blood pressure. Conclusions: We developed two models that demonstrated a high negative predictive value, which allowed us to distinguish patients with low risk and determine patients who can be hospitalized and sent from the ED to the floor. These easy-to-use models can be used at the ED.