Abstract

Objective Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain a biventricular circulation (BV). We assessed FV efficacy by comparing survival and postnatal circulation between FV (performed between 2005 and 2012) and natural history (NH) cohorts in a retrospective, multicenter study. Methods Main outcome measures were overall survival, BV survival, and survival after birth. Secondary outcomes were hemodynamic change, and left heart growth. We created a propensity score model including 54/67 FV and 60/147 NH fetuses. Analyses used logistic, Cox, or linear regression models with inverse probability of treatment weighting (IPTW), restricted to fetuses with propensity score 0.14-0.9 to create a final cohort for analysis of 42 FV and 29 NH. Results FV was technically successful in 59/67 at median age 26 weeks (21-34). There was a 7/72 (10%) procedure-related loss and 22/53 (42%) FV babies were delivered at <37 weeks. IPTW demonstrated improved survival of liveborn infants following FV: HR 0.38 (95%CI: 0.23-0.64), p=0.0001, after adjusting for circulation and postnatal surgical center. Similar proportions were BV: FV 36% and NH 38% and survival was similar between final circulations. Successful-FV showed improved hemodynamic response, and less deterioration of left heart growth, compared with NH (p=0.01 to 0.002). Conclusions We report improvements in fetal hemodynamics and preservation of left heart growth following successful-FV compared to NH. While the proportion of those achieving a BV outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation out to 10 years. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with NH and therefore the risk-benefit ratio remains uncertain. We recommend a carefully designed trial, incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy versus surgical strategy can be clearly demonstrated.