Peak Oxygen Consumption Scaled to Body Composition Is Associated With Mortality and Morbidity in People With a Fontan Circulation

Background: Peak oxygen consumption (peak $\dot{V}$O₂) is traditionally scaled by body mass, but it is most appropriately scaled by fat-free mass. However, it is unknown whether peak $\dot{V}$O₂ scaled by fat-free mass is associated with mortality and morbidity in people with a Fontan circulation. The aim of this study was to assess the associations between different expressions of peak $\dot{V}$O₂ with mortality and morbidity in people with a Fontan circulation.

Methods and results: Eighty-seven participants (aged 24.1±7.3 years; 53% women) with a Fontan circulation completed a cardiopulmonary exercise test and a dual-energy x-ray absorptiometry scan. Cox proportional hazard regressions models assessed the association (hazard ratio [HR]) between different expressions of peak $\dot{V}$O₂ with a composite outcome of Fontan failure (FF). Participants were followed up for a median of 6.5 years (95% CI, 6.4-6.9). Individuals experiencing FF (n=10/87) had a significantly lower absolute peak $\dot{V}$O₂. In univariable models, peak $\dot{V}$O₂ ratio scaled to body mass was not significantly associated with FF (HR, 0.91; P=0.111). However, peak $\dot{V}$O₂ scaled by fat-free mass (HR, 0.90; P=0.020) or lean mass (HR, 0.90; P=0.017) was significantly and inversely associated with FF. These associations remained significant after adjusting for age, sex, and peak respiratory exchange ratio.

Conclusions: The association between peak $\dot{V}$O₂ and FF is improved when scaled to measures of body composition. Applied clinically, a 1-unit increase in peak $\dot{V}$O₂ scaled to fat-free mass or lean mass is associated with a ≈10% lower risk of FF.