Examination of elevated myocardial extracellular volume and exercise capacity in pediatric Fontan patients at moderate altitude

BACKGROUND: Diffuse myocardial fibrosis, as measured by T1 (longitudinal relaxation time) mapping and extracellular volume, may be associated with ventricular dysfunction in the Fontan circulation. However, the relationship between diffuse myocardial fibrosis and exercise tolerance, an early and clinically meaningful marker of Fontan physiology, remains incompletely characterized, particularly in pediatric populations. OBJECTIVE: To evaluate the association between CMR-derived markers of diffuse myocardial fibrosis (native T1 and ECV) and exercise tolerance in pediatric patients with Fontan circulation compared with healthy controls. MATERIALS AND METHODS: A retrospective cohort study of pediatric patients with Fontan circulation who underwent clinically indicated cardiovascular magnetic resonance (CMR) with native and post-contrast T1 mapping between 2019 and 2022 was performed. Global native T1 and ECV were quantified and compared with age- and scanner-matched controls. Cardiopulmonary exercise testing-derived VO₂ max and catheterization parameters obtained within 24 months of CMR were analyzed. Associations between myocardial fibrosis markers and functional measures were assessed using correlation analyses. RESULTS: A cohort of 64 pediatric Fontan patients (median age 11.0 years, interquartile range 7.0-14.0; age range <18 years), and 41 pediatric controls, was stratified by field strength and ventricular dominance. Fontan patients demonstrated increased native T1 values across varying field strengths of 1.5 T (1,035.9 ± 48.7 ms vs 983.8 ± 29.0 ms, P<0.001) and 3 T (1,292.8 ± 53.5 ms vs 1,257.8 ± 41.5 ms, P=0.033), and significantly elevated ECV compared to controls (25.6 ± 3.5% vs 23.2 ± 2.1%, P=0.007). There was no significant difference in native T1 or ECV between dominant right and left ventricles. VO₂ max was markedly reduced in Fontan patients compared to controls (1.2 ± 0.4 liters per minute (LPM) vs 2.5 ± 0.7 LPM, P<0.001). While a broad-inverse correlation between ECV and VO₂ max did not reach statistical significance across the full cohort (R=-0.19, P>0.05), time since Fontan surgery was inversely correlated with ECV (R=-0.27, P<0.05), and localized subgroup correlations emerged between native T1 and exercise capacity. CONCLUSIONS: Markers of myocardial fibrosis were elevated among Fontan patients compared to healthy controls. Fontan patients were shown to have reduced exercise tolerance compared to controls as measured by VO2 max. While myocardial ECV is elevated in pediatric Fontan patients, its relationship with impaired exercise capacity is complex and subgroup-specific, suggesting a need for additional study and functional decline may be driven by multifactorial etiologies.