Abstract 12806: Attributable Mortality Benefit of Digoxin Treatment in Hypoplastic Left Heart Syndrome After the Norwood Operation

Introduction: Observational studies have demonstrated an association between digoxin treatment and lower interstage mortality after Norwood operation for hypoplastic left heart syndrome (HLHS), but the attributable mortality benefit has not been measureable without a clinical trial. Application of an instrumental variable can overcome confounding by indication and unmeasured confounding through pseudo-randomization. Methods: A multicenter retrospective cohort study of neonates with HLHS born 1/1/2007-12/31/2021, undergoing a Norwood operation at Pediatric Health Information Systems Database hospitals, and surviving >14 days post-operatively was performed evaluating the association of digoxin and 1-year transplant-free survival. Traditional multivariable logistic regression models were supplemented with instrumental variable analyses using hospital-specific 60-day likelihood of administering digoxin. Results: The study population included 5,148 subjects treated at 47 hospitals (63% male, 46% non-Hispanic white); 44% (n=2,184) received digoxin. Receipt of digoxin was associated with superior 1-year transplant-free survival in unadjusted analyses (85% vs. 82%, p=0.02). This persisted after adjustment for measurable confounders (OR: 0.66, p<0.001) and in an instrumental variable analysis (OR: 0.71, p=0.01, Figure). Conclusions: This observational study of patients with HLHS after Norwood used instrumental variable techniques to demonstrate a significant benefit in one-year transplant-free survival attributable to digoxin. In the absence of clinical trial data, this should encourage the use of digoxin in this vulnerable population..