Myopenia and exercise capacity in adult fontan patients: the association between appendicular lean mass and cardiopulmonary performance

Background Although patients with the Fontan circulation generally display reduced muscle mass in comparison to healthy controls, the severity of myopenia exhibits considerable inter-individual variability. Purpose This study aimed to evaluate differences in clinical parameters between Fontan patients with preserved muscle mass and those with myopenia. Material and Methods 62 adult Fontan patients were recruited into the prospective cohort study. In all patients, Bioelectrical Impedance Analysis (BIA) and the 6-Minute Walk Test (6MWT) were performed, and Hand Grip Strength (HGS) was measured. Using results from BIA and validated population-specific reference data, Appendicular Lean Mass (ALM) Index (ALMI) Z-scores were calculated. All patients were divided into two groups according to the ALMI Z-scores: Normal Muscle Mass Group with ALMI Z-score >-1 (N=48), and Muscle Deficit Group with ALMI Z-score ≤-1 (N=14). Groups were analysed using Mann-Whitney U test, χ2 and Fisher's Exact Test (where appropriate). The Spearman correlation was used to check for correlations between parameters. Results The median age of all patients was 21 years (IQR 19-25). The systemic ventricle was dominant: left in 21 patients (33.9%); right in 37 patients (59.7%). Patients with muscle deficit were significantly younger (19 vs 23, p=0.001), and had lower BMI (18.1 vs 22.7 kg/m2, p<0.001). Interestingly, there was no significant difference in the morphology of the systemic ventricle, and no significant ventricle dysfunction was observed in the muscle deficit group. Regarding cardiopulmonary exercise testing parameters, patients with muscle deficit had significantly lower values of oxygen pulse [O2pulse] (9 vs 11 ml/beat, p=0.02), peak oxygen uptake [VO2peak] (1.27 vs 1.77 l/min, p=0.01), and percent achieved of predicted VO2peak (58.5% vs 66%, p=0.03). The minute ventilation/CO2 production slope (VE/VCO2slope) was significantly higher in these patients (40.4 vs 35.3, p=0.01), while oxygen uptake efficiency slope (OUES) was significantly lower (1.45 vs 2.2, p=0.03). HGS was significantly lower in patients with a muscle deficit, in both raw values (23.8 vs 35.7 kg, p=0.004), and HGS Z-scores (-2.14 vs -0.69, p=0.0009). There was no significant difference in 6MWT distance. In the entire cohort, ALM correlated significantly (p<0.05) with O2pulse (r=0.86), VO2peak (r=0.79) [Figure 1], OUES (r=0.68), and HGS (r=0.74). HGS correlated significantly with VO2peak (r=0.71), and O2pulse (r=0.66). 6MWT distance correlated significantly with normalized VO2peak (r=0.58), and O2pulse (r=0.42). Conclusions Muscle deficit in Fontan patients is significantly associated with impaired exercise capacity and reduced ventilatory efficiency. The presence of myopenia in younger patients suggests an early-onset process. Therapies aimed at preserving or increasing muscle mass may be critical for improving the long-term functional prognosis of the Fontan patients.Figure 1- Correlation between ALM and VO2peak