Evaluation of Exercise Capacity in Fontan Patients and Effects of Pulmonary Vasodilators

The assessment of exercise capacity is critical in evaluating patients with congenital heart disease, particularly those with Fontan circulation.Among various parameters, oxygen consumption oxygen consumption (VO 2 ) is considered the most reliable indicator of exercise capacity.Peak VO 2 represents the maximum ability of the body to utilize oxygen during intense exercise and is a comprehensive reflection of cardiovascular, pulmonary, and muscular systems.It is widely used in cardiopulmonary exercise testing for clinical evaluation, prognostic assessment, and exercise prescription.Other parameters such as respiratory rate, minute ventilation, the minute ventilation/carbon dioxide production (VE/VCO 2 ) at the anaerobic threshold, and VO 2 at the anaerobic threshold (AT) are also considered.However, these provide less direct information on actual exercise capacity.Respiratory rate and minute ventilation are influenced by breathing patterns and pulmonary function, while VE/VCO 2 and VO 2 AT reflect ventilatory efficiency and submaximal capacity, respectively.Pulmonary vasodilators, including phosphodiesterase 5 (PDE5) inhibitors like sildenafil and udenafil, and endothelin-1 receptor antagonists such as bosentan and macitentan, have been studied for their effects on exercise capacity in Fontan patients.Sildenafil, a PDE5 inhibitor, showed reduced respiratory rate and minute ventilation at peak exercise, with improved ventilatory efficiency at the anaerobic threshold in a double-blind, placebo-controlled, crossover trial.However, it did not affect peak VO 2 , but improvement at the anaerobic threshold was observed in patients with single left or mixed ventricular morphology or baseline brain natriuretic peptide ≥100 pg/mL.1) Bosentan, an endothelin receptor antagonist, demonstrated favorable outcomes in the Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption (TEMPO) study, including increased peak VO 2 , longer exercise test duration, and improved New York Heart Association (NYHA) functional class.However, improvement of peak VO 2 was modest in some subsets of patients, and the overall clinical impact remains debated.2) However, recent studies have failed to demonstrate the favorable effects of vasodilators on peak VO 2 .