Key result
Better endothelial function correlates moderately with higher peak VO2 in youth with Fontan circulation.
Why the study?
Fontan circulation carries high morbidity and mortality, partly driven by impaired exercise capacity, muscle deficits, and endothelial dysfunction, prompting evaluation of the associations among these parameters in pediatric patients.
RCT (n=137)
randomized
Effect estimate: r = 0.50
p-value: p=<0.001
In pediatric patients with Fontan circulation, lower aerobic capacity is significantly associated with reduced endothelial function, leg lean mass, strength, and mobility.
Baseline associations in pediatric Fontan patients are hypothesis-generating; randomized intervention results needed before practice change.
Background Fontan circulation carries high morbidity and mortality, driven in part by impaired exercise capacity, muscle deficits, and endothelial dysfunction. In a pediatric cohort with Fontan circulation, we examined associations between exercise capacity, endothelial function, and muscle parameters before enrollment in a randomized exercise intervention. Methods Patients aged 8-19 years who have Fontan circulation were included. Exclusion criteria included New York Heart Association class IV, active illness, protein-losing enteropathy, pacemaker, or cognitive delay. Assessments included cardiopulmonary exercise testing (peak VO 2 ), endothelial function testing (reactive hyperemia index [RHI]), fasting lipid profile, dual-energy x-ray absorptiometry and dynamometry (muscle mass and strength), and functional movement screening (FMS). Results Among 137 participants (median age 12.7 years; 53% single right ventricle), median time since Fontan was 8.6 years. Peak VO 2 was 1402 ± 509 mL/min (75.7% ± 17.9% predicted; 31.1 ± 7.4 mL/kg/min indexed). RHI was 1.45 ± 0.6; NOx 22.2 ± 17.4 μmol/L. The low-density lipoprotein cholesterol level was 65.8 ± 18.9 mg/dL. Length-adjusted leg lean mass, handgrip strength, and leg extension strength z scores were –1.02 ± 1.0, –0.76 ± 0.9, and –0.70 ± 1.0, respectively. The FMS score averaged 11.9 ± 3.0. Peak VO 2 correlated with RHI ( r = 0.50), lnRHI ( r = 0.51), FMS ( r = 0.30) (all P < 0.001), and length-adjusted leg lean mass z score ( r = 0.25, P = 0.003). Indexed and percent-predicted peak VO 2 also correlated with FMS ( r = 0.31 and 0.30, respectively) and high-density lipoprotein ( r = 0.24 and r = 0.25, respectively). Conclusion In youth with Fontan circulation, lower aerobic capacity was associated with lower endothelial function, leg lean mass, strength, and mobility, underscoring the interdependence of cardiovascular, vascular, and musculoskeletal health. Clinical Trial NCT04195451
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Lui et al. (2025) conducted an RCT in Fontan circulation (n=137). Exercise intervention (baseline analysis) was evaluated on Correlation between peak VO2 and reactive hyperemia index (RHI) (r = 0.50, p=<0.001). In youth with Fontan circulation, peak VO2 significantly correlated with reactive hyperemia index (r=0.50, P<0.001), functional movement screening (r=0.30), and leg lean mass (r=0.25, P=0.003).
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