# Exploring Serum Biomarker Levels in Tetralogy of Fallot, Hypoplastic Left Heart Syndrome, and Healthy Children

## TL;DR

This study explores serum biomarker levels in children with heart conditions like Tetralogy of Fallot and Hypoplastic Left Heart Syndrome, comparing them to healthy children to identify potential disease-specific patterns.

## Contribution

The study provides new insights into serum biomarker profiles in pediatric heart disease, highlighting differences in collagen metabolism and cardiac remodeling markers.

## Key findings

- TOF patients had higher PICP, MMP-1, and NT-proBNP compared to younger controls.
- rTOF and HLHS patients showed elevated PIIINP, MMP-1, and MMP-9 compared to older controls.
- Collagen metabolism biomarkers and MMP-1 were elevated across all disease groups.

## Abstract

Serum biomarkers have emerged as tools for diagnosis and management in adult heart disease but are less investigated in the pediatric population. This exploratory study reports biomarker profiles in unrepaired tetralogy of Fallot (TOF), repaired TOF (rTOF), hypoplastic left heart syndrome (HLHS) following Fontan surgery, and healthy controls. We compared circulating biomarker patterns between TOF, rTOF, HLHS, and control groups, aiming to characterize potential disease-specific profiles and generate hypotheses for future research. We prospectively enrolled subjects and collected single-time blood samples for analysis. We measured: microRNA-21 (miR-21), soluble suppression of tumorigenicity-2 (sST-2), galectin-3 (Gal-3), procollagen type-I carboxy-terminal pro-peptide (PICP), procollagen type-III amino-terminal pro-peptide (PIIINP), metalloproteinases (MMP-1/MMP-9), and NT-proBNP. We included 207 patients: TOF (n = 75), rTOF (n = 60), HLHS (n = 11), and healthy controls (n = 60). Compared to the younger controls, TOF patients had higher PICP, MMP-1, and NT-proBNP. Compared to older controls, rTOF patients had higher PIIINP, MMP-1, MMP-9, and NT-proBNP; and HLHS patients had higher PIIINP and MMP-1. Collagen metabolism biomarkers and MMP-1 were elevated across disease groups. Gal-3 was associated with age in HLHS. No disease-specific patterns were observed; however, differences from controls suggest cardiac remodeling in TOF and HLHS.

The online version contains supplementary material available at 10.1007/s00246-025-03935-0.