What Limits Cardiorespiratory Fitness in Adolescents with Fontan Circulation: An Integrated Hemodynamic and Pulmonary Perspective

Cardiorespiratory fitness (CRF) is strongly associated with morbidity and mortality in patients with Fontan circulation. However, the factors influencing CRF during adolescence remain incompletely understood. The primary aim of this study was to investigate the associations between CRF and ventricular function represented by end-diastolic pressure (VEDP), the transpulmonary pressure gradient (TPG), somatic growth (height) and pulmonary diffusing capacity (DL_CO/VA). The secondary aim was to assess the prevalence of exercise oscillatory ventilation (EOV) and its physiological associations. In this national, cross-sectional study, 44 adolescents (median age 16.6 years) with Fontan circulation underwent cardiopulmonary exercise testing, heart catheterization and pulmonary function assessment. Peak oxygen uptake (V̇O₂peak) was modelled as the dependent variable in a multiple linear regression with VEDP, TPG, height, and DL_CO/VA as predictors. Logistic regression was used to identify physiological associations of EOV. The multiple regression model for absolute V̇O₂peak explained 61% of the overall variance. Lower VEDP and greater height were independently associated with higher V̇O₂peak. When V̇O₂peak was expressed relative to body mass, TPG also became associated with higher V̇O₂peak, while greater height and lower VEDP remained associated. This model explained 30% of the variance. DL_CO/VA was not independently associated with V̇O₂peak. EOV was observed in 50% of patients but showed no association with V̇O₂peak, hemodynamic, or pulmonary variables. In adolescents with Fontan circulation, lower resting VEDP and somatic growth were associated with higher CRF, reflecting more efficient hemodynamics. Pulmonary diffusing impairment and EOV were common but not significantly associated with lower CRF.