The purpose of the current investigation is to demonstrate the efficacy of high-dose furosemide plus small-volume hypertonic saline solution and a Sodium-Glucose cotransporter-2 (SGLT-2) inhibitor among patients admitted for acute exacerbation of heart failure, in determining a significant increase in diuresis and natriuresis. It is also accompanied by a rapid reduction in body weight and a substantial decrease in hospitalization length without compromising renal function.

All enrolled patients will undergo a comprehensive physical examination post-randomization. This examination will involve a meticulous assessment of congestive heart failure (CHF) indicators, encompassing the measurement of bodyweight (BW) (taken in the morning before breakfast), supine and standing blood pressure (BP [average of 3 readings]), and heart rate (HR). Fasting blood samples will be collected daily throughout the hospital stay to ascertain serum laboratory parameters (creatinine, sodium, potassium, and N-terminal pro b-type natriuretic peptide) until achieving a clinically stabilized condition. Urine output will be measured daily, also to detect creatinine, sodium, potassium urinary levels and glycosuria. Additionally, an electrocardiogram and echocardiogram (to derive EF using the modified Simpson rule with 2 cross-sectional views [4- and 2-chamber apical views], right atrium volume (RA volume, ml/m2), left atrial volume (LA volume ml/m2), inferior vena cava diameter (IVC diameter, cm), interventricular septum thickness at end-diastole (IVSd, cm), right ventricular basal diameter at end-diastole (RVD1 basal, mm), right ventricular mid diameter at end-diastole (RVD2 mid, mm), right ventricular longitudinal diameter at end-diastole (RVD3 long, mm), right ventricular outflow tract at proximal and distal (RVOT prox and distal, mm), fractional area change (FAC, %), E wave dominant (m/s), A wave dominant (m/s), tricuspid valve E/A wave ratio (E/ATrV), tissue Doppler echocardiography (TDE, ms), eak velocity in early diastole of tricuspid annulus (TDI) (m/s), tricuspid valve e'/a' ratio (TDI, m/s), peak systolic velocity tricuspid annulus (Pulsed TDI, m/s) will be conducted prior to hospital discharge.

Patients will be categorized into 4 groups: the first group will undergo 15 minutes intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily along with severe water restriction (< 500 mL); the second group will receive intravenous furosemide as a bolus twice daily and severe water restriction (< 500 mL) without hypertonic saline solutions; the third group will undergo 15 minutes intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily, severe water restriction (< 500 mL), and SGLT2 inhibitors (Dapagliflozin); the fourth group will receive intravenous furosemide as a bolus without hypertonic saline solutions twice daily, severe water restriction (< 500 mL), and SGLT2 inhibitors (Dapagliflozin). The groups will maintain a normal sodium intake (120 mmol/day). The daily furosemide dosage will be determined based on diuretic requirements, urinary output, BP readings, and the severity of congestion signs and symptoms. The hypertonic saline solutions dosage for each patient (in groups 1 and 3) will be determined following these guidelines: for serum Na values of 125 milliequivalent/L, the hypertonic saline solutions concentration will be 4.6%; for serum Na values between 126 and 135 milliequivalent/L, the hypertonic saline solutions concentration will be 3.5%; and for serum Na values of 135 milliequivalent/L, the hypertonic saline solutions concentration will range between 1.4% and 2.4%. Throughout the study period, patients diagnosed with Heart Failure with Reduced Ejection Fraction (HFrEF) will receive angiotensin converting enzyme inhibitors, sartans, angiotensin receptor-neprilysin inhibitors, beta blockers, and mineralocorticoid inhibitors. The objective is to optimize heart failure therapy in alignment with the most recent European Society of Cardiology guidelines published in August 2023. Daily, there will be meticulous monitoring of body weight (in the morning before breakfast) and 24-hour urinary volume measurements. Serum and urinary laboratory parameters will be assessed daily until achieving a clinically stabilized condition, defined as a shift in New York Heart Association functional class to at least second b and reaching the ideal body weight calculated via the Lorenz formula. Upon attaining this clinically stabilized state, intravenous administration of furosemide and hypertonic saline solutions will cease, transitioning to oral furosemide administration, while maintaining the unchanged optimal therapy post-discharge according to the standard protocol.

Inclusion Criteria:

• acute heart failure;
• diabetes type 2.

Exclusion Criteria:

• low estimated glomerular filtration rate;
• hypernatremia;
• diabetes type 1;
• non-cardiac causes of dyspnea;
• cardiogenic shock;
• recent occurrence of Acute Coronary Syndrome;
• ketoacidosis;
• hyperosmolar hyperglycemic syndrome.