Exercise Limitations in Fontan Circulation: A Systematic Review and Meta-analysis of Peak Oxygen Uptake

The degree to which individuals with Fontan circulation (FC) experience exercise limitations and the underlying physiological mechanisms remains unclear. Thus, we sought to quantify the magnitude of peak oxygen consumption ( $\dot{V}$ O₂peak) impairment and its determinants in individuals with FC and age-matched healthy controls (CON).

PubMed, Web of Science, and Scopus were searched from January 1980 through July 2025. Studies were included if they reported $\dot{V}$ O₂peak or its Fick determinants derived from a cardiopulmonary exercise test and compared FC with CON. Random-effects models were used for pooled data analysis, and meta-regressions were used to explore key moderators of age and time after Fontan surgery.

Pooled analysis demonstrated significantly reduced $\dot{V}$ O₂peak in FC vs CON (19 studies, n = 893; weighted mean difference: 17.2 mL/kg/min, 95% confidence interval: -20.9 to -14.3 mL/kg/min). Meta-regressions revealed that age significantly moderated the weighted mean difference for relative $\dot{V}$ O₂peak (β = -5.77 mL/kg/min; 95% confidence interval: -11.27 to -0.27; P = 0.041). Peak exercise oxygen pulse, heart rate, systolic blood pressure, and arterial oxygen saturation were significantly lower in FC compared with CON, whereas peak exercise stroke volume did not differ significantly between the groups.

Exercise capacity is markedly impaired in individuals with FC due to central and peripheral limitations, and the magnitude of this decline accelerates with time after surgery. These findings highlight the importance of early identification and targeted (exercise) intervention to mitigate long-term functional decline.