Circulating Biomarkers in Failing Fontan Circulation: Current Evidence and Future Directions

Area of Science:

• Cardiology
• Biomarker Research
• Pediatric and Adult Congenital Heart Disease

Background:

• Patients with Fontan circulation face lifelong risks of multi-organ complications.
• Increasing adult survival necessitates improved long-term follow-up and early sequelae detection strategies.
• Non-invasive monitoring tools are urgently needed for Fontan physiology assessment.

Purpose of the Study:

• To comprehensively review current evidence on circulating blood biomarkers for monitoring Fontan physiology.
• To analyze biomarkers related to cardiac dysfunction, systemic inflammation, endothelial dysfunction, hepatic/renal impairment, and bone metabolism in Fontan patients.

Main Methods:

• Narrative review of existing studies on serum biomarkers in Fontan physiology.
• Critical analysis of biomarkers reflecting key pathological mechanisms of Fontan failure.
• Exploration of potential applications of artificial intelligence (AI), machine learning (ML), and 'omics' studies.

Main Results:

• Several biomarkers show potential in reflecting systemic impairments and end-organ involvement in Fontan patients.
• Current data are insufficient for standardized clinical biomarker recommendations due to small sample sizes and heterogeneous populations.
• Limited longitudinal data hinders the establishment of evidence-based guidelines.

Conclusions:

• Large-scale, prospective, multi-center research is essential to identify clinically useful biomarkers for Fontan patients.
• AI/ML approaches can integrate heterogeneous datasets for better analysis.
• 'Omics'-based studies offer promise for discovering novel biomarkers and pathways, advancing precision medicine in Fontan patient management.