Predictors of exercise capacity in adult Fontan patients: insights from cardiopulmonary exercise testing after total cavopulmonary connection

Background Congenital heart defects palliated with the Fontan procedure result in a functional single ventricle, most commonly of right or left ventricular morphology. Cardiopulmonary exercise testing (CPET) is an established tool for functional assessment and may provide prognostic information. Despite improved survival into adulthood, predictors of functional capacity remain incompletely defined. This study aimed to develop a statistical model to identify predictors of exercise capacity, measured by peak oxygen uptake (peak VO₂), in adult Fontan patients at a single high-volume tertiary ACHD centre in Poland. Methods Among 172 patients after total cavopulmonary connection (TCPC) followed between 2011 and 2025, 142 underwent at least one CPET. The first complete evaluation was included. After determining ventricular morphology, 122 patients were analysed: 81 with a left single ventricle (LSV) and 41 with a right single ventricle (RSV). Patients with undetermined or mixed morphology were excluded. All patients underwent standardised evaluation including physical examination, laboratory testing (NT-proBNP), ECG, Holter monitoring, echocardiography, liver elastography, and CPET. Variables potentially influencing peak VO₂ were preselected based on literature and clinical experience, including sex, age, age at Fontan, laboratory results, physical examination, echocardiographic parameters, and ventricular morphology. Continuous variables correlated with peak VO₂ and nominal variables with group differences (Student’s t-test) were included in the regression model. The model included variables with p<0.200. Results Baseline characteristics are in Table 1; significant correlations with peak VO₂ are in Table 2. The regression model had an adjusted R² of 0.38, indicating that 38% of peak VO₂ variability was explained by the included predictors. The overall model was statistically significant (p < 0.0001; F = 8.067; df1 = 10; df2 = 101). Independent predictors of peak VO₂ were male sex (B = 0.320, t = 3.120, p = 0.002), left ventricular morphology (B = –0.234, t = –2.957, p = 0.004), and peak heart rate during CPET (B = 0.355, t = 4.288, p < 0.001). Remaining variability may be due to unmeasured factors, highlighting the multi-factorial nature of functional limitation. Conclusions In adult Fontan patients, exercise capacity is significantly influenced by sex, ventricular morphology, and peak heart rate during CPET. Male sex, left ventricular morphology, and higher peak heart rate were associated with better performance. A substantial proportion of variability remains unexplained, suggesting multiple clinical, haemodynamic, and extracardiac factors contribute to exercise limitation. These findings may guide individualised assessment and management of adult Fontan patients.