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The Fontan operation has revolutionized the outcome of patients with univentricular hearts. However, long-term morbidity and mortality remain high and exercise intolerance in common in this population. Previous studies have failed to demonstrate a clear relation between exercise capacity, expressed as peak oxygen consumption (pVO2), and the risk of death in contrast with other congenital and non-congenital cohorts. Aims To investigate the correlates of pVO2 in the Fontan population and its relation to mortality. Methods Data were collected retrospectively on consecutive patients with a Fontan circulation who underwent a cardiopulmonary exercise test (CPET) between 2005–2019. Clinical and exercise data were collected at the time of CPET and patients were followed thereafter. Cox regression analysis was used to assess the association between exercise parameters and mortality. Different methods of estimating predicted pVO2 were compared in their impact on the prognostic value of pVO2. Results A total of 152 patients were included. Mean age at CPET was 28.9±9.3 years and 74 (48.7%) were female. The majority of patients had a total cavo-pulmonary connection (TCPC; 53.3%) followed by atrio-pulmonary (2.1%) and other Fontan variants 4.6%. The majority of patients reported no limitation on physical activity [AC1] (NYHA class I, 91, 62.3%). Baseline oxygen saturation was 93±5% and 26 (17.6%) patients had a persistent fenestration. On exercise, pVO2 was 21.9±7.4ml/min and was significantly reduced in the majority of asymptomatic patients (56.1±17.4% predicted according to the Wasserman/Hansen (WH) formula). The VE/VCO2 slope was raised (&amp;gt;33) in 92 (60.9%) patients. A total of 88 (58.7%) patients had an impaired heart rate reserve, and were unable to achieve a heart rate of at least 70% predicted. Over a median follow-up of 4.6 [2.5–8.9] years, 25 (16.4%) patients died. pVO2 expressed as ml/min was the only exercise parameter related to mortality in this cohort (HR 0.93, 95% CI: 0.87–0.99, p=0.03).pVO2 was even more strongly related to mortality when expressed as percentage of predicted using the WH formula (HR 0.76, 95% CI: 0.59–0.98, p=0.03), but not the Jones formula for predicted pVO2 (HR 0.83, 95% CI: 0.67–1.02, p=0.08). Additional predictors of outcome included NYHA class (no asymptomatic patients died), use of loop diuretics and a non-TCPC circulation, but not age or sex were not (Figure 1). On multivariable analysis, percent predicted pVO2 (WH) remained a predictor of outcome (HR per 10 unit increase 0.65, 95% CI: 0.46–0.93, p=0.017) with NYHA class and diuretic treatment, and with the type of Fontan operation. Conclusion A clear relation between pVO2 and mortality could be demonstrated in this Fontan population by using unadjusted pVO2, or appropriate estimates of predicted pVO2. CPET can thus be used for the risk stratification of Fontan patients, providing that care is taken in the way that pVO2 is reported and interpreted. Figure 1 Funding Acknowledgement Type of funding source: None

Peak oxygen uptake on cardio pulmonary exercise testing predicts mortality in adult Fontan patients