Individuals with a Fontan circulation have shorter telomeres compared with controls, mirroring an accelerated aging phenotype, which is more pronounced in patients with a systemic right ventricle, those with adverse hemodynamics, and is associated with having a higher burden of comorbidities.
Key Findings
Results
Patients with Fontan circulation had significantly shorter leukocyte telomeres compared with controls.
Fontan cohort N=90, control cohort N=59
Median age was 14.90 (IQR, 10.99–20.69) years in the Fontan cohort and 15.20 (IQR, 11.11–16.42) years in controls
Telomeric DNA to single-copy gene (T/S) ratio was 1.04 (IQR, 0.96–1.14) in Fontan patients versus 1.13 (IQR, 0.96–1.24) in controls
Difference was statistically significant (P=0.021)
Biological aging was assessed by leukocyte telomere length through quantitative polymerase chain reaction
Results
Fontan patients with systemic right ventricles had shorter telomeres than those without systemic right ventricles.
T/S ratio was 1.02 (IQR, 0.93–1.08) in patients with systemic right ventricles versus 1.05 (IQR, 1.00–1.17) in those without
Difference was statistically significant (P=0.047)
This finding indicates the accelerated aging phenotype is more pronounced in the systemic right ventricle subgroup
Results
Lower superior vena cava (SVC) saturation was associated with shorter telomeres in Fontan patients.
β=0.007 (95% CI, 0.002–0.012); P=0.013
Lower SVC saturation reflects reduced mixed venous oxygen saturation, a marker of reduced cardiac output and increased oxygen extraction
This hemodynamic variable was independently associated with telomere shortening
Results
Lower cardiac index was associated with shorter telomeres in Fontan patients.
β=0.06 (95% CI, 0.012–0.108); P=0.016
Cardiac index is a measure of cardiac output adjusted for body surface area
This finding links worse cardiac hemodynamic performance to accelerated biological aging
Results
Higher systemic vascular resistance was associated with shorter telomeres in Fontan patients.
β=−0.007 (95% CI, −0.014 to −0.001); P=0.023
Elevated systemic vascular resistance is a marker of adverse Fontan hemodynamics
The negative beta coefficient indicates that as systemic vascular resistance increases, telomere length decreases
Results
Patients with telomere loss greater than 50 bp per year experienced significantly higher rates of increasing comorbidities at follow-up.
Median follow-up was 13.07 months
46.7% of patients with telomere loss (>50 bp/year) experienced an increase in comorbidities
Only 20.5% of patients with no change or an increase in telomere length experienced an increase in comorbidities
Difference was statistically significant (P<0.001)
This suggests telomere shortening rate may have prognostic value for clinical deterioration
What This Means
This research suggests that children and young adults born with complex heart defects requiring a Fontan circulation — a surgical procedure that reroutes blood flow when one of the heart's pumping chambers is missing or non-functional — show signs of accelerated biological aging compared to peers without heart disease. The study measured telomere length, which are protective caps on chromosomes that naturally shorten as people age, in 90 Fontan patients and 59 healthy controls of similar age. Fontan patients had measurably shorter telomeres, indicating their cells were biologically 'older' than expected for their chronological age.
The accelerated aging was even more pronounced in Fontan patients whose right ventricle — normally a lower-pressure chamber — was forced to do the work of the high-pressure left ventricle (called a 'systemic right ventricle'). Additionally, patients with worse circulatory efficiency, reflected by lower cardiac output, lower oxygen levels in venous blood, and higher resistance in the blood vessels, showed the shortest telomeres. Over roughly 13 months of follow-up, nearly half of patients whose telomeres were shortening rapidly developed new or worsening health problems, compared to only about one in five patients whose telomere length was stable or improving.
This research suggests that biological aging is a real and measurable phenomenon in Fontan patients, even in childhood and adolescence, and that it may help explain why these individuals are at higher risk for a wide range of health problems as they grow older. The findings open the door to investigating whether treatments aimed at slowing biological aging — separate from treating the heart defect itself — could improve long-term health outcomes for this population.
Woo J, Vincent A, Kushwaha A, Gan S, Ichimura S, Egorova A, et al.. (2026). Accelerated Aging Fontan Phenotype Is Associated With Systemic Right Ventricles and Adverse Hemodynamics.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.048352