Thinking Outside the “Flow-Mediated” Box: An Analysis of Aortic Dilation in 100 Fetuses with Tetralogy of Fallot Compared to Matched Controls

Abstract

ABSTRACTBackgroundAortic dilation in tetralogy of Fallot (TOF) is primarily attributed to increased aortic flowin utero. An alternative hypothesis is abnormal neural crest cell migration, with unequal septation of the truncus arteriosus resulting in a larger aorta and inherently hypoplastic pulmonary artery (PA). If so, we hypothesize the aorta to PA ratio (Ao:PA) in TOF is stable throughout gestation, and the total sum of dimensions of the great arteries is similar to controls.MethodsWe performed a single-center retrospective study of all fetuses with TOF (2014-2020) and gestational age-matched controls. We compared sums of diameters, circumferences, and cross-sectional areas of the aorta and PA and evaluated the Ao:PA across gestation in TOF with pulmonary stenosis (TOF-PS) and atresia (TOF-PA). We analyzed data with two-tailed t-tests and Pearson’s correlation.ResultsThere were 100 fetuses with TOF (36% TOF-PA) with median gestational age of 31 weeks [IQR 26.5, 34.4] and median maternal age of 34 years [IQR 30, 37]. There were no differences in sums of great artery dimensions between TOF-PS and controls. In TOF-PA, sums were significantly lower than controls. The Ao:PA was stable throughout gestation.ConclusionsThe aorta in fetal TOF is large but grows proportionally throughout gestation, with a sum of great artery dimensions similar to controls. TOF-PA appears to be distinct from TOF-PS (with overall smaller dimensions), and is a group that warrants further investigation. In conclusion, our findings do not support the flow-mediated model of aortic dilation in TOF, and instead suggest an intrinsic developmental mechanism.Clinical PerspectiveWhat’s New?The aorta in fetal Tetralogy of Fallot (TOF) is large, but grows proportionally throughout gestation with a total sum of great artery dimensions similar to controls.Fetuses with TOF with pulmonary atresia have smaller great artery dimensions than TOF with pulmonary stenosis; this distinct group warrants further investigation.Our findings suggest that aortic dilation in TOF may be secondary to an intrinsic developmental mechanism, rather than from increased flow to the aortain utero.What are the clinical implications?The mechanisms of aortic dilation in fetal TOF have not been previously investigated.While aortic dilation is commonly seen in TOF, the degree of its progression over time and risk of dissection are not well understood.A better understanding of the etiology of aortic dilation in TOF could help to inform management decisions, particularly regarding the need for prophylactic surgical repair.