The Fontan Dapagliflozin Pilot Study (FonDap)

Background: Patients with Fontan are prone to sequelae related to chronic elevations in central venous pressures. Interventions that improve venous pressures without compromising ventricular filling may therefore be of benefit. Methods We conducted a multi-center, open label, single arm pilot study of 4 weeks of dapagliflozin 10mg in adult patients with Fontan. The primary outcome was change in resting peripheral venous pressure (PVP). Secondary outcomes included changes in post-exercise PVP, peak VO2, Ve/VCO2, oxygen pulse, oxygen uptake efficiency slope (OUES), total body water, and patient reported health status according to the ACHD PRO. Results The total of 29 patients were enrolled between 11/1/2023 and 2/3/2026 across 2 centers, of whom 26 completed all study procedures. Average age was 31.2 years and 19 had a morphologic left ventricle. Dapagliflozin decreased PVP by 1.3mmHg (IQR -2.6, 0.4, p=0.012) with a greater effect in those with higher baseline PVP. Dapagliflozin improved patient reported health status and resulted in a trend towards an improvement in peak VO2 (0.2ml/kg/min, IQR -0.9, 2.2, p=0.064) and oxygen pulse (0.3ml/beat, IQR -0.6-1.1, p=0.074) without any impact on other cardiopulmonary exercise test parameters or total body water. Dapagliflozin was well tolerated in participants with no significant adverse events. Conclusions Dapagliflozin decreased PVP and improved patient reported health status in adult patients with Fontan over 4 weeks of therapy and was generally well tolerated.