Cardiorenal Syndrome: Characteristics and Prognostic Impact in Advanced Heart Failure

Cardiorenal Syndrome: Characteristics and Prognostic Impact in Advanced Heart Failure

Advanced heart failure (AHF) represents the end stage of chronic heart failure with reduced ejection fraction and affects up to 10% of patients with heart failure. These patients have refractory disease despite optimal guideline-directed medical therapy, and their management is discussed within a multidisciplinary "Heart Team".

Renal dysfunction is highly prevalent in this population. The coexistence of cardiac and renal dysfunction has been classified under the entity of cardiorenal syndrome. Impaired renal function is an independent predictor of adverse cardiovascular and renal outcomes, including death, heart failure decompensation, worsening renal function, and the need for renal replacement therapy. However, patients with AHF remain a particularly complex population, and the lack of longitudinal biological data and limited understanding of the dynamics of cardiorenal syndrome in relation to therapeutic interventions make prognosis assessment and individualized management challenging.

In addition, little is known about renal tubular function in AHF, despite its central role in hydro-electrolytic balance regulation. Biomarkers of tubular injury such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) have shown prognostic value in therapeutic studies, but their relationship with cardiac function and outcomes in advanced heart failure remains insufficiently characterized.

The primary objective of this study is to evaluate renal function parameters and their evolution over time through measurement of glomerular filtration rate (GFR) and assessment of tubular function in patients with advanced heart failure, and to investigate their association with major adverse cardiovascular events.

This is a prospective, single-center RIPH2 cohort study including 100 patients aged 18 to 75 years managed for advanced heart failure at the Louis Pradel Cardiovascular Hospital (Hospices Civils de Lyon, France). Patients will be followed according to standard care at 6, 12, 18, and 24 months. More comprehensive nephrological and cardiological evaluations will be performed at baseline, 12 months, and 24 months. Biobanking and quality-of-life questionnaires will also be conducted during these visits. Blood and urine samples will be collected at baseline and 12 months for NGAL et KIM-1 analysis. In addition, a subgroup of 50 consenting patients without contraindications will undergo multiparametric non-contrast renal MRI combined with tissue sodium quantification using 23Na MRI of the leg.

Inclusion Criteria:

• Written informed consent signed by the patient,

• Age ≥ 18 years and ≤ 75 years,

• Patient with advanced heart failure confirmed by criteria of severe cardiac dysfunction documented in a stable condition, with at least one of the following parameters at baseline:

  • LVEF ≤ 35%,
  • Elevated BNP or NT-proBNP levels (>200 ng/L for BNP and >1000 ng/L for NT-proBNP),

• NYHA class ≥ 3,

• At least one hospitalization for heart failure decompensation within the past 24 months,

• Optimized medical treatment for heart failure according to French/European cardiology guidelines at the maximum tolerated dose for >30 days.

Exclusion Criteria:

• Presence of severe extracardiac disease with a life expectancy < 1 year,
• Patient with end-stage renal disease (GFR <15 mL/min/1.73 m²) or on dialysis,
• History of heart, kidney, or other solid organ transplantation,
• Patient in cardiogenic shock,
• INTERMACS profile ≤ 3,
• Pregnant, parturient, or breastfeeding women*,
• Individuals deprived of liberty by judicial or administrative decision,
• Individuals under psychiatric care,
• Individuals admitted to a health or social institution for purposes other than research,
• Adults under legal protection (guardianship or curatorship),
• Individuals not affiliated with a social security system or equivalent coverage.
• Contraindication to multiparametric renal MRI combined with tissue sodium measurement using non-contrast 23Na MRI of the leg (including inability to undergo MRI as judged by the investigator).