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

Summary

While the Fontan operation improves survival for patients with a functional single ventricle, complications like heart failure remain prevalent during follow-up, causing frequent hospitalizations and reduced quality of life. Currently, there are no evidence-based heart failure therapies or guidelines for patients with Fontan palliation. There is growing interest in using sodium-glucose cotransporter 2 inhibitors (SGLT2i) to optimize cardiac conditions in this group. SGLT2i's observed benefits relate to protective effects on cardiac energy metabolism, renal function, sympathetic activation, inflammation, oxidative stress, erythropoiesis, and vascular function. Therefore, SGLT2i may represent a new therapeutic agent to improve exercise capacity and ventricular function in patients with Fontan circulation. This prospective, open-label, single-arm clinical trial investigates the FDA-approved drug dapagliflozin. An open-label design is utilized due to the relatively small cohort of patients with complex underlying hearts. The trial will be conducted at Hong Kong Children's Hospital (the sole pediatric cardiology center in Hong Kong) and Queen Mary Hospital (the largest tertiary referral center for adult congenital heart patients). The total study duration is 2 years. Subjects will participate for 3 months, receiving oral dapagliflozin 10mg once daily. The primary endpoint is VO2 max (maximum rate of oxygen consumption) during cardiopulmonary exercise testing at 3 months. Secondary assessments include questionnaires, history taking, physical examinations, 12-lead electrocardiogram, blood tests, echocardiography, bioelectrical impedance analysis, and urine pregnancy tests. If the hypothesis holds true, clinical translation of this project will: i) Improve long-term outcomes and quality-of-life for Fontan patients, reducing the healthcare burden from repeated heart failure hospitalizations; ii) Revolutionize the management of Fontan-associated heart failure by introducing SGLT2i as a novel, evidence-based therapy locally and globally; iii) Pave the way for multicenter international trials evaluating SGLT2i in the Fontan population and broader congenital heart diseases.

Eligibility

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

Conditions6

Interventions1

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