Biomarker profile in stable Fontan patients

Area of Science:

• Cardiology
• Immunology
• Biomarker Research

Background:

• The growing population of adults with congenital heart disease (CHD) presents complex cases for cardiologists.
• Single ventricle Fontan palliation patients represent a particularly complex subset of CHD with high morbidity and mortality.
• The underlying factors contributing to the early mortality in Fontan patients remain largely unknown.

Purpose of the Study:

• To analyze biomarker expression in stable Fontan outpatients.
• To compare biomarker levels in Fontan patients to age, gender, and race-matched controls.
• To identify molecular factors associated with clinical events and outcomes in Fontan patients.

Main Methods:

• Biomarker expression was analyzed in 44 stable Fontan outpatients.
• Fontan patients were compared to 32 healthy controls.
• Statistical analyses, including multivariate modeling, were used to assess biomarker associations.

Main Results:

• Fontan patients showed elevated levels of inflammatory cytokines (TNF-α, IL-6), GDF-15, β2-macroglobulin, SDF-1α, Collagen IV, Renin, Cystatin C, uPAR, Troponin-I, and Adiponectin compared to controls.
• Within one year, 50% of Fontan patients experienced hospitalizations, arrhythmias, or worsening hepatic function.
• Growth Derived Factor-15 (GDF-15) was significantly increased in Fontan patients with clinical events and correlated with longer Fontan duration.

Conclusions:

• Fontan patients exhibit upregulated clinical and molecular biomarkers, indicating a state of chronic systemic dysregulation.
• Elevated GDF-15 levels are associated with clinical events in Fontan patients.
• VEGF-D and Collagen IV levels are linked to changes in MELDXI, a marker of liver dysfunction.