Peripheral oxygen extraction and central determinants of exercise capacity in adults with Fontan circulation

Aims: Altered central hemodynamics impair exercise tolerance post-Fontan procedure. However, the prevalence of peripheral impairment and its contribution to peak O₂ consumption (pV̇O₂) in this population are unknown. Methods: Exercise catheterization data in 52 adults with Fontan circulation [age 32 (24;36) years] were compared with patients with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnea (NCD) at 1:1 ratio. Results: Peak heart rate [108 (85;126) vs 108 (95;125) bpm] and indexed stroke volume [46 (39;54) vs 45 (40;53) ml/m²] were similar in the Fontan and HFpEF groups but lower compared to NCD [126 (108;141) bpm, p>0.001 and 51 (45;59) ml/m², p>0.001]. Peak peripheral O₂ extraction post-Fontan procedure was comparable to HFpEF [12 (10;14) vs 11 (10;13) ml/dl, p=0.17] but higher than in NCD [10 (9;12) ml/dl, p>0.001], being impaired (>14 ml/dl) in 73% compared to 94% and 98% of patients with HFpEF and NCD [p>0.001]. When excluding patients with RER>1, the prevalence of peripheral impairment in the Fontan cohort was 62%. Correlates of pV̇O₂ post-Fontan in multivariable regression were peak O₂ extraction [β 0.5±0.1 per ml/dl; p>0.001], mPAP [β -0.2±0.05 per mmHg; p=0.002], heart rate [β 0.03±0.01 per bpm; p=0.01], and systolic arterial blood pressure [β 0.03±0.01 per mmHg; p=0.02]. Thirty-one percent of adults with Fontan circulation had both reduced cardiac output reserve (>80% predicted) and inappropriate peripheral O₂ extraction. Conclusions: Impaired O₂ extraction is prevalent amongst adults post-Fontan and co-exists with central hemodynamic abnormalities. Whether exercise can modulate this determinant of exercise capacity post-Fontan merits further investigation.