Fetal cardiac intervention in hypoplastic left heart syndrome with intact or restrictive atrial septum, systematic review, and meta-analysis

To investigate outcomes of fetuses with hypoplastic left heart syndrome (HLHS) with an intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI PubMed, Scopus, and Web of Science were searched systematically from inception until April 2023. Outcomes were classified by those who had FASI and those who had expectant management (EM). To estimate the overall proportion of each endpoint, a meta-analysis of proportions was employed using a random-effects model. Heterogeneity was assessed using the I-2 value. Thirty-two studies reporting on 746 fetuses with HLHS and I/RAS met our inclusion criteria. Eleven studies (123 fetuses) were in the FASI group and 21 studies (623 fetuses) were in the EM group. Among the 123 FASI cases, 107 (87%) were reported to be technically successful. The mean gestational age (GA) at diagnosis was comparable between the groups (26.2 weeks FASI vs. 24.4 weeks EM group). The mean GA at FASI was 30.4 weeks (95% CI 28.5, 32.5). The mean GA at delivery was also comparable (37.7 weeks FASI vs. 38.1 weeks EM group). Neonatal outcomes, including live birth, neonatal death, and survival to hospital discharge pooled proportions, were also comparable between groups (live birth: 92% (95% CI 64, 99) FASI versus 93% (95% CI 79, 98) in EM, neonatal death: 32% (95% CI 11, 65) FASI versus 30% (95% CI 21, 41) EM, survival to hospital discharge: 37% (95% CI 25, 52) FASI versus 52% (95% CI 42, 61) EM). Age at neonatal death was higher in the FASI group (mean: 17 days FASI vs. 7.2 days EM group). There was a lower rate of postnatal atrial restrictive septum in the FASI group 38% (95% CI 17, 63) compared to the EM group 88% (95% CI 57, 98). Our review shows variations across centers in the selection criteria and techniques used for FASI. Although survival including livebirth, neonatal death, and survival to hospital discharge did not differ between groups, the procedure may translate into a less restrictive septum at birth. Future multicenter studies are needed to better identify the subset of cases that might have improved outcomes, use standardized definitions, unified techniques, utilize core outcome set, and assess long-term benefits.

Automated summary

This study investigated the outcomes of fetuses with hypoplastic left heart syndrome (HLHS) and intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI). The study found no differences in survival rates between the two groups, but FASI may lead to a less restrictive septum at birth. Future multicenter studies are needed for better identification of cases with improved outcomes and standardized techniques and definitions.