Predictors of sildenafil effects on exercise capacity in adolescents and adults with Fontan circulation

Objective: A single dose of sildenafil improves exercise capacity in Fontan patients. However, a recent study failed to show a long-term effect of sildenafil. This study evaluated whether there are factors that might predict sildenafil effects. Methods: We studied 36 patients (16-42 years, 14 female) with univentricular heart after various modifications of the Fontan surgery (13 APC, 16 AVC, 7 TCPC). They performed two cardiopulmonary exercise tests, with at least 120 min rest and a single dose of 50 mg sildenafil in between. Results: After sildenafil administration, patients improved their peak oxygen uptake from 64.5 to 67.3 % predicted (p = 0.0003) without change in ventilatory efficiency (V̇_E/V̇CO₂ slope), oxygen saturation (SpO ₂) at rest or at peak exercise, respiratory exchange ratio. In addition, resting systolic blood pressure was slightly reduced after sildenafil administration. There was a moderate negative correlation of this improvement to baseline peak oxygen uptake (r = -0.395; p = 0.017). The change in peak oxygen uptake could not be correlated to time of surgery, type of surgery, NT-pro-BNP, or to other clinical data. Nevertheless, all four patients with NT-pro-BNP levels higher than 1,000 pg/ml had the most prominent improvements in exercise capacity. Conclusions: Fontan patients have an improved exercise capacity after a single dose of sildenafil. Patients with worse baseline peak oxygen uptake profit more.