Outcomes in infants with restrictive atrial septum and pre-stage 1 palliation septal intervention

Infants diagnosed with hypoplastic left heart syndrome (HLHS) who have a restrictive or intact atrial septum (RAS) have worse outcomes in single center analyses. Multi-center studies are lacking, and optimal identification and management of atrial restriction remains unclear.

Multicenter retrospective cohort study of infants undergoing stage 1 palliation (S1P) from 2016 to 2024 and included in the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC). Infants were classified based on atrial septal anatomy and intervention as follows: RAS with pre-S1P intervention, RAS without pre-S1P intervention, and no RAS. Primary analysis compared outcomes between infants with RAS and pre-S1P intervention versus infants without RAS. Primary outcomes included operative survival, post-S1P length of stay (LOS), and one-year mortality. Secondary outcomes included peri-operative and S1P discharge characteristics. Analyses were adjusted for demographic and clinical factors through multivariable regression.

Among 3644 infants who underwent S1P at 70 centers, 5% (n=164) had RAS with pre-S1P septal intervention, 10% (n=369) had RAS without intervention, and 85% (n=3111) did not have RAS. Compared to infants without RAS, those with RAS and pre-S1P septal intervention had greater pre-operative instability with increased inotrope use (43% vs 15%), mechanical ventilation (57% vs 19%), and persistent shock (18% vs 7%), all p<0.001, and were more likely to undergo hybrid S1P (23% vs 10%, p<0.001). In risk-adjusted analysis, infants with RAS and pre-S1P septal intervention had higher operative mortality (aOR 2.01 [95% CI 1.22-3.33] p=0.007) and one-year mortality (aOR 2.2 [1.44,3.38] p<0.001) than infants without RAS.

RAS identifies a high-risk phenotype with early instability and excess early and one-year mortality. These findings highlight the need for improved risk stratification and more effective, standardized atrial decompression strategies for infants with clinically significant atrial restriction.