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

Official title

Association of Urinary Chloride and Sodium Dynamics With Multiparametrically Assessed Residual Congestion in Acute Heart Failure (CLORINA-IC)

Overview

The goal of this observational study is to learn how changes in urinary sodium and chloride levels relate to fluid overload and short-term outcomes in patients hospitalized with acute heart failure (AHF). The main questions it aims to answer are: * Do changes over time in urinary sodium and chloride reflect how well excess fluid is being removed during hospitalization? * Are these changes associated with residual congestion at discharge and with the risk of worsening heart failure or death after discharge? Participants hospitalized for AHF and treated with intravenous diuretics as part of their usual care will have clinical assessments, blood and urine tests, and echocardiographic evaluations collected at several time points during their hospital stay. Researchers will also record clinical outcomes, including worsening heart failure or death, at 30 days and 3 months after discharge.

Detailed description

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.

Primary outcome measures

• Residual Congestion at 72 Hours [Time frame: 72 hours after admission.]

Secondary outcome measures (6)

• Worsening Heart Failure at 30 days [Time frame: From hospital discharge to 30 days thereafter.]
• Worsening Heart Failure at 3 months [Time frame: From hospital discharge to 3 months thereafter.]
• 30-day all-cause mortality [Time frame: From hospital discharge to 30 days thereafter.]
• 3-month all-cause mortality [Time frame: From hospital discharge to 3 months thereafter.]
• 30-day combined event (all-cause mortality or worsening heart failure) [Time frame: From hospital discharge to 30 days thereafter.]
• 3-month combined event (all-cause mortality or worsening heart failure) [Time frame: From hospital discharge to 3 months thereafter.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Spain · 4 centers

• Hospital de Olot i Comarcal de la Garrotxa — Olot
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Universitario Puerta de Hierro Majadahonda — Majadahonda
• Hospital Clínico Universitario de Valencia — Valencia

Publications

• Campos J, Llacer P, Croset F, Garcia M, Perez C, Perez A, Vergara M, Cevallos P, Fabregate M, Fernandez C, Ruiz R, Useros D, Menacho M, Dominguez M, Perez E, Nunez J, Manzano L. Dynamics of urinary chloride and sodium and their link to decongestion in acute heart failure and preserved ejection fraction: NACLOCRo-HF study. ESC Heart Fail. 2025 Dec;12(6):4336-4348. doi: 10.1002/ehf2.15436. Epub 2025 PMID 41078081

Identifiers

NCT: NCT07597512 · PI25/00126 · PI25/00126

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗