Effect of dapagliflozin on heart failure with reduced ejection fraction in children

Objective To explore the efficacy and safety of dapagliflozin therapy in children with heart failure with reduced ejection fraction. Methods This was a retrospective cohort study based on electronic medical records. For the retrospective cohort study, 32 children with heart failure with reduced ejection fraction diagnosed at Shanghai Children's Medical Center and Fujian Children's Hospital from June 2021 to June 2023 and who were treated with dapagliflozin were enrolled. For pediatric patients weighing 10 kg, dapagliflozin was administered at a dosage of 0.2 mg/kg/d. Patients with a body weight ranging from 10 kg to less than 20 kg (20 weight ≥10 kg) received dapagliflozin at a dose of 2.5 mg/d. Those weighing between 20 kg and less than 30 kg (30 weight ≥20 kg) were prescribed dapagliflozin at 5 mg/d. For patients weighing 30 kg or more, the initial dose of dapagliflozin was 5 mg/d, which was increased to 10 mg/d after one month. 42 children treated during the same period without dapagliflozin were included as the control group. All children were treated with standard guideline-directed triple combination of ACEI/ARNI, β -blocker, and aldosterone receptor antagonist. Clinical characteristics, underlying diseases, cardiac function ratings, left ventricular ejection fraction, B-type natriuretic peptide, and blood biochemical indexes were collected. Changes in cardiac function ratings, left ventricular ejection fraction, and B-type natriuretic peptide at 24 (±2) weeks of treatment were observed; the incidence of hospitalization or death due to exacerbation of heart failure at 24 (±2) weeks of treatment was observed secondarily. Adverse medicine events such as hypoglycemia or hypotension were also observed during treatment. Results Among the 32 children, 20 were male and 12 were female, aged (6.32 ± 4.00) years; weight (22.19 ± 12.66) kg. The underlying diseases included dilated cardiomyopathy in 25 cases, dilated cardiomyopathy combined with complete left bundle branch block in two cases, postoperative congenital heart disease in four cases, and atrial tachycardia in one case. At 24 (±2) weeks of treatment, left ventricular ejection fraction level significantly increased compared with baseline ( P 0.001); B-type natriuretic peptide decreased ( P 0.001); and New York Heart Association (NYHA) cardiac function ratings improved significantly ( P = 0.034). Compared with the control group, children in the dapagliflozin group showed greater improvement in left ventricular ejection fraction ( P = 0.032) and NYHA cardiac function rating ( P = 0.038), whereas no significant difference was observed in BNP levels ( P = 0.071). Three children developed urinary tract infection during the administration of the medication, and three children developed hypotension, while no other adverse reactions, such as hypoglycemia or hepatic or renal function impairment, were observed. Conclusion Dapagliflozin was associated with improvements in left ventricular ejection fraction, BNP, and NYHA cardiac function classification in children with heart failure with reduced ejection fraction. No hospitalization or death due to the deterioration of heart failure and no serious adverse reactions were observed. The treatment was generally well tolerated, and the weight-stratified dosing strategy showed acceptable short-term safety.