Urinary Chloride and Sodium Changes and Residual Congestion in Acute Heart Failure

This is a prospective, multicenter observational study. A minimum required sample size of n = 223 patients completing the study is planned. This study will include patients hospitalized for AHF and treated with intravenous diuretics. Clinical, biochemical, echocardiographic parameters, and circulating biomarkers (NT-proBNP, CA125, sST2, bioADM, and CD146) will be collected serially during hospitalization. Additionally, clinical events (worsening heart failure and/or all-cause mortality) will be recorded at 30 days and 3 months after discharge. Decongestion will be assessed using a multiparametric approach, incorporating clinical evaluation, echographic parameters, and estimated plasma volume status.

Inclusion criteria

• Provision of written informed consent prior to any study-related procedures;
• Age ≥ 18 years;
• Episode of AHF requiring hospital admission and treatment with intravenous furosemide;
• New York Heart Association (NYHA) functional class II-IV;
• NT-proBNP >1000 pg/mL or BNP >250 pg/mL, measured within a period not exceeding 24 hours prior to inclusion;
• Transthoracic echocardiogram performed within the previous 24 months. All LVEF categories will be included: reduced LVEF (<40%), mildly reduced LVEF (41-49%), and preserved LVEF (≥50%). In patients with preserved LVEF (HFpEF), congruent structural and/or functional echocardiographic abnormalities are required (left ventricular hypertrophy defined as septal or posterior wall thickness ≥11 mm, E/e' >9, or left atrial volume >32 mL/m²);
• Signs of fluid overload, with at least two of the following: jugular venous distension (at least up to the sternocleidomastoid level, ~10 cm), lower limb edema, ascites, or pleural effusion confirmed by chest radiography or lung ultrasound
• Treatment with oral furosemide at a dose of at least 40 mg/day within the previous month.

Exclusion criteria

• Symptomatic hyponatremia or plasma sodium level ≤125 mmol/L;
• Hemoglobin <9 g/dL;
• Hypokalemia: serum potassium <3 mEq/L;
• Chronic kidney disease with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m²;
• Hemodynamic instability at admission, defined as symptomatic hypotension;
• Acute coronary syndrome, cardiogenic shock, or admission to the intensive care unit (ICU);
• Severe infection (e.g., pneumonia, sepsis, leukocyte count ≥12,000/μL, C-reactive protein >50 mg/L, or positive COVID-19 test);
• Requirement for inotropic agents;
• Life expectancy <3 months or, in the investigator's judgment, inability to comply with study procedures.