Four weeks of dapagliflozin 10mg daily reduced resting peripheral venous pressure by 1.3 mmHg (p=0.012) in 26 adult Fontan patients (mean age 31.2 years) across two centers, with larger reductions in those with higher baseline pressures. The drug also improved patient-reported health status and showed non-significant trends toward better peak VO2 (+0.2 ml/kg/min, p=0.064) and oxygen pulse (+0.3 ml/beat, p=0.074), with no adverse events reported.
Fontan physiology — where a single ventricle drives circulation without a subpulmonary pump — creates chronically elevated venous pressures that progressively damage the liver, gut, and lymphatics. Current pharmacological options are limited and largely borrowed from standard heart failure protocols with little disease-specific evidence. SGLT2 inhibitors like dapagliflozin have reshaped heart failure management broadly, but their mechanism here appears distinct: the venous pressure reduction occurred without changes in total body water, suggesting hemodynamic rather than purely diuretic effects — an intriguing mechanistic signal worth pursuing.
Critical limitations temper enthusiasm: this is a single-arm, open-label pilot with just 26 completers and no control group, making placebo effects on patient-reported outcomes impossible to rule out. A 1.3 mmHg venous pressure reduction, while statistically significant, has uncertain clinical translation over years. As a preprint posted to medRxiv and not yet peer-reviewed, these findings require validation in a randomized, controlled trial before clinical adoption. Still, this represents a genuinely promising signal for a population with few therapeutic advances.