Abstract Body (Do not enter title and authors here): Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are proven to reduce risk of cardiovascular death and hospitalization for heart failure (HF) in adults with reduced or preserved ejection fraction (EF). There are limited data on SGLT2i use in pediatric HF.

Hypothesis: Addition of SGLT2i to standard HF medical therapy in children with left ventricular (LV) systolic dysfunction is associated with improved clinical outcomes.

Methods: Single-center observational analysis of 65 pediatric patients (≤ 21 years old) with LV systolic dysfunction (n=44 dilated cardiomyopathy; n=21 repaired biventricular congenital heart disease) who had SGLT2i added to standard HF medical therapy since January 2020. Patients must have received SGLT2i for minimum of 3 months to be included. Patients with single ventricular physiology or already supported by a ventricular assist device (VAD) were excluded.

Results: Median age at SGLT2i initiation was 11.2 years (range 2 months to 21 years), 54% were female, and 46% were started on SGLT2i (89% dapagliflozin; 11% empagliflozin) during an inpatient hospitalization. Median daily SGLT2i dose received was 5 mg or 0.14 (IQR 0.11-0.17) mg/kg/day. Sixty percent had a HF hospitalization within the prior year preceding SGLT2i start. Chronic HF medications at latest follow-up included sacubitril/valsartan (82%) or ACE inhibitor (6%), beta-blocker (83%), and mineralocorticoid receptor antagonist (77%). Median follow-up was 16.2 months (IQR 8.1-27.1). Median LVEF increased significantly from 35% (IQR 27-41) to 41% (IQR 32-52) and B-type natriuretic peptide (BNP) decreased from 300 pg/mL (IQR 84-728) to 86 pg/mL (IQR 18-308) (both p<0.01). There was a significant difference in NYHA/Ross Class from baseline (I: 12%; II: 62%; III: 20%; IV: 6%) to latest follow-up (I: 35%; II: 49%; III: 6%; IV: 9%) (p<0.01) with 32% improved, 62% unchanged, and 6% worsened. HF hospitalization occurred for 20% of the patients at median time of 7.9 months (IQR 3.2-16.5) after SGLT2i initiation. Eleven percent of the cohort were listed for transplant, died, or underwent VAD implant at latest follow up.

Conclusion: Long-term use of SGLT2i in addition to standard HF medications in children with LV systolic dysfunction is associated with significant improvement in LVEF, BNP, and NYHA/Ross class. Use of SGLT2i in pediatric HF is evolving and further larger scale studies should be supported to determine efficacy.