Telomere Loss Predicts Increasing Comorbidity Burden in Pediatric and Adult Fontan Patients

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Summary of  Journal of the American Heart Association https://doi.org/10.1161/JAHA.125.048352
Dr. Jennifer P. Woo et al.

Points

Researchers at Stanford Cardiovascular Institute compared ninety patients with Fontan circulation against fifty nine healthy controls to evaluate leukocyte telomere length and accelerated biological aging.
Measurements revealed that single ventricle Fontan patients exhibited significantly shorter telomeres even at young ages compared to individuals with normal heart anatomy and function.
Telomere shortening was markedly more pronounced in patients with a systemic right ventricle and correlated with reduced cardiac output higher vascular resistance and lower blood oxygenation.
Longitudinal follow up showed that nearly fifty percent of patients experiencing telomere loss developed additional medical comorbidities compared to twenty percent with stable telomere lengths.
Study authors concluded that tracking cellular aging markers provides a novel biological framework for monitoring long term disease progression and developing targeted therapies for Fontan patients.

Summary

This study evaluated cellular markers of accelerated biological aging in patients living with a Fontan circulation, a palliative surgical routing for single-ventricle congenital heart defects. Published in the Journal of the American Heart Association by researchers at the Stanford Cardiovascular Institute, the investigation examined leukocyte telomere length to determine whether altered systemic hemodynamics promote premature biological aging. The research sought to establish correlations between telomere attrition, systemic ventricular morphology, physiological hemodynamic parameters, and progressive clinical comorbidity burden in a predominantly adolescent cohort.

The cross-sectional study compared 90 children and adults with Fontan circulation against 59 age-matched controls with normal cardiac anatomy and function. Quantitative analysis revealed that Fontan patients exhibited significantly shorter leukocyte telomeres compared with controls, an effect observed even at young ages. Telomere shortening was significantly more pronounced in patients whose single functioning pump was a systemic right ventricle rather than a left ventricle. Furthermore, shorter telomeres correlated with adverse hemodynamic features, including reduced cardiac index, increased systemic vascular resistance, and lower venous oxygen saturation in upper-body return.

At follow-up approximately one year later, nearly 50% of patients demonstrating active telomere loss experienced an increased comorbidity burden, compared to approximately 20% of patients with stable or lengthening telomeres. The authors conclude that an accelerated biological aging phenotype exists in Fontan patients, linked directly to adverse hemodynamics and systemic right ventricular strain. While longitudinal studies are required to establish predictive causality for heart transplantation or survival, monitoring telomere attrition provides a novel framework for tracking long-term disease progression and developing anti-aging therapeutic strategies.

Link to the article: https://www.ahajournals.org/doi/10.1161/JAHA.125.048352

References

Woo, J. P., Vincent, A. G. B., Kushwaha, A., Gan, S., Ichimura, S., Egorova, A. D., Veldtman, G. R., Wyss‐Coray, T., Le Guen, Y., & Reddy, S. (2026). Accelerated aging fontan phenotype is associated with systemic right ventricles and adverse hemodynamics. Journal of the American Heart Association, 15(18), e048352. https://doi.org/10.1161/JAHA.125.048352