Intrinsic histological abnormalities of aortic root and ascending aorta in tetralogy of Fallot - Evidence of causative mechanism for aortic dilatation and aortopathy

Background - Dilatation of the aortic root is a known feature in tetralogy of Fallot (TOF) patients with pulmonary stenosis (PS) or pulmonary atresia (PA). We hypothesized that intrinsic histological abnormalities of the aortic wall present since infancy are an important causative factor leading to aortic root dilatation. Methods and Results - We examined the aortic histology of 17 cases with TOF and PS/PA from our cardiac morphology archive and compared them with a control group of normal aortas. Measured circumference of the aortic root at the sinotubular junction and at the ascending aorta was indexed to the left ventricle. Aortic walls were studied by light microscopy with the use of various stains. Seventeen TOF cases (7 with PS, 10 with PA) including 7 infants, 2 children, and 8 adults were compared with 11 hearts with normal aorta. Aortic root circumference to left ventricular index and ascending aortic circumference to left ventricular index were 1.24 +/- 0.25 and 1.37 +/- 0.24, respectively, in the TOF group versus 0.89 +/- 0.10 and 0.88 +/- 0.11, respectively, in the control group (P < 0.001). Histological changes of grade 2 or 3 were present in 29% (medionecrosis), 82% (fibrosis), 35% (cystic medial necrosis), and 59% (elastic fragmentation) in the ascending aorta of the TOF group. Histology grading scores were significantly higher in the TOF group (median score, 7; range, 1 to 12) compared with normal controls (median score, 2; range, 0 to 6) and correlated with the ascending aortic circumference to left ventricular index (r = 0.525, P = 0.03). Conclusions - There are marked histological abnormalities in the aortic root and ascending aortic wall of patients with TOF present from infancy, suggesting a causative mechanism for subsequent aortic root dilatation.