Exercise Capacity, Endothelial Function, Muscle Mass, and Strength in Pediatric Patients With Fontan Circulation

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 VO₂), 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 VO₂ 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 VO₂ 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 VO₂ 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.