Researchers identified 22 distinct cardiovascular biomarkers in 31 Fontan circulation patients compared to 52 controls, with FGF23 and HAOX1 showing the strongest negative correlations with ejection fraction. HAOX1, a peroxisomal oxidase involved in cellular redox metabolism, and FGF23, a bone-derived hormone regulating phosphate homeostasis, emerged as potential predictors of declining heart function where traditional BNP measurements failed. This finding addresses a critical gap in monitoring patients with Fontan circulation—a complex surgical reconstruction for single-ventricle congenital heart defects affecting thousands globally. Current surveillance relies heavily on imaging, but these biomarkers could enable earlier detection of cardiovascular deterioration through simple blood tests. The phosphate-regulating FGF23 connection suggests potential metabolic pathways linking bone health to cardiac function in this vulnerable population. However, this preprint study's small cohort size and observational design limit causal conclusions. The work requires peer review and larger validation studies before clinical implementation. While incremental rather than paradigm-shifting, these biomarkers could meaningfully improve long-term care for Fontan patients who face inevitable cardiovascular complications as they age.