Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease, particularly in patients with a univentricular heart and Fontan circulation. This physiology is associated with progressive morbidity and the development of a failing Fontan (FF), most often related to systolic or diastolic ventricular dysfunction. Therapeutic options remain limited. Dapagliflozin, a sodium–glucose cotransporter 2 inhibitor recommended for left-sided HF, may provide functional benefits in this population. We aimed to evaluate the impact of dapagliflozin on functional capacity in adults with FF related to ventricular dysfunction.

We conducted a 6-month prospective, multicenter, observational study including adults (> 18 years) with FF confirmed by right heart catheterization within the previous 6 months. FF was defined by elevated ventricular filling pressures (ventricular end-diastolic pressure or pulmonary artery wedge pressure ≥ 15 mmHg) associated with systolic dysfunction (ejection fraction ≤ 40%) or diastolic dysfunction (ejection fraction ≥ 41%). Patients with severe atrioventricular valve regurgitation, elevated pulmonary vascular resistance, Fontan circuit obstruction, pregnancy, or systolic blood pressure < 95 mmHg were excluded. The primary endpoint was change in peak oxygen consumption (VO _2max ) assessed by cardiopulmonary exercise testing between baseline and 6 months. Secondary endpoints included NYHA class, quality of life (KCCQ-12), oxygen saturation, NT-proBNP, ventricular function, HF hospitalizations, diuretic dose, biological parameters, blood pressure, and safety.

Fifty-one patients were included (median age 35 years [30–40], 62.5% female). In preliminary analyses of 22 patients, dapagliflozin was associated with significant improvement in VO _2max at 6 months ( P = 0.028), KCCQ-12 score ( P = 0.011), and oxygen saturation ( P = 0.013). Treatment was well tolerated, with two discontinuations due to recurrent urinary tract infections and no major safety concerns.

In adults with failing Fontan and ventricular dysfunction, dapagliflozin was associated with improved functional capacity and quality of life and showed a safety profile.