The Effect of Dapagliflozin on Exercise and Cardiac Functional Status of Patients After Fontan Procedure

Eligible patients with Fontan circulation who meet all predefined inclusion and exclusion criteria will be recruited from Queen Mary Hospital and Hong Kong Children's Hospital in Hong Kong. Prospective candidates will undergo a screening interview conducted by the research staff. During this interview, the objectives of the clinical trial, the required procedures, and any potential risks will be comprehensively explained. Prior to formal enrollment and the initiation of any study-specific procedures, written informed consent will be legally obtained from the patient or their designated legal guardian.

The study protocol involves a series of scheduled clinical assessments, beginning with a baseline evaluation at Visit 1. During this initial visit, patients will undergo a comprehensive medical history review and a physical examination. Baseline vital signs, including blood pressure, pulse rate, and resting oxygen saturation via pulse oximetry, will be recorded. Routine cardiovascular evaluations will include standard 12-lead electrocardiography. Unless performed within the preceding three months, a comprehensive laboratory panel will be drawn; this includes a complete blood count, renal and liver function tests, calcium and phosphate levels, N-terminal pro b-type natriuretic peptide (NT-proBNP), hemoglobin A1c, fasting glucose, and a lipid profile. Additionally, a urine pregnancy test will be administered to all women of childbearing potential. To establish baseline patient-reported outcomes, participants will complete either the Kansas City Cardiomyopathy Questionnaire (KCCQ) or the Paediatric Quality of Life Inventory (PedsQL).

Specialized cardiovascular diagnostics and subsequent follow-up evaluations will be conducted at Visit 1 (Week 4 ± 1) and Visit 3 (Week 12 ± 1). At the Week 12 follow-up visit, patients will complete a re-administration of the KCCQ or PedsQL questionnaires. During both specified visits, patients will undergo cardiopulmonary exercise testing (CPX) under the direct supervision of a cardiologist. This testing is designed to evaluate critical functional parameters, including peak oxygen consumption (VO₂), total functional capacity measured in metabolic equivalents (METs), oxygen pulse as a surrogate for stroke volume, the anaerobic threshold (VO₂ AT), and ventilatory efficiency (VE/VO₂).

In conjunction with the exercise testing, comprehensive echocardiography will be performed by an independent echocardiographer at Visit 1 and Visit 3, though the baseline scan may be waived if a comprehensive assessment is available from the preceding three years. The echocardiographic analysis will utilize color Doppler flow imaging for the semi-quantitative assessment of systemic atrioventricular (AV) valve regurgitation severity. Conventional pulsed-wave Doppler will be employed to measure early and late diastolic AV valve inflow velocities, allowing for the calculation of the AV systolic-to-diastolic ratio based on the regurgitant jet, which serves as a clinical correlate for ventricular end-diastolic pressure. Furthermore, pulsed-wave tissue Doppler imaging (TDI) will be conducted in the apical four-chamber view. By positioning the sample volume at the lateral AV annulus, researchers will record systolic, early diastolic, and late diastolic velocities to calculate the TDI-based myocardial performance index (MPI). Finally, speckle-tracking echocardiography (STE) will be applied to accurately quantify the systolic and diastolic myocardial deformation, or strain, of the single ventricle.

Inclusion criteria

• Patients with a functional single ventricle and who have undergone Fontan procedure
• Adolescents aged ≥ 12 years with body weight ≥30kg and adults

Exclusion criteria

• Planned cardiac and/or non-cardiac surgery in 3 months
• Arrhythmias requiring change in therapy in recent 6 months
• Intervention procedure within 6 months prior to enrollment
• Documented structural abnormalities of the Fontan circulation
• Chronic kidney disease stages 4 to 5
• Inability to perform cardiopulmonary test
• Recent use of SGLT2 inhibitors within 6 months
• Known hypersensitivity to SGLT2 inhibitors
• History of diabetic ketoacidosis
• Recent symptomatic hypoglycaemia within 6 months
• Insulin dependent diabetes mellitus
• History of perineum infection
• Recent urinary tract infection within 6 months
• Recent genital infection within 6 months
• Other known contraindications to SGLT2 inhibitor
• Pregnancy or breast feeding