Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease

Background: Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. Methods: We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak VO2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (VE/VCO2 slope), were recorded. Results: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak VO2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak VO2 (p = 0.003) and the highest VE/VCO2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak VO2 (p = 0.003) compared with other patients. Peak VO2 was negatively correlated with pulmonary vascular resistance (r =-0.411, p < 0.001). Conclusions: Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.