Aortic Hypoplasia in Homozygous Familial Hypercholesterolemia

H familial hypercholesterolemia (HFH) is a rare condition characterized primarily by early development of malignant atherogenesis, frequently terminating in premature myocardial infarction and cerebrovascular accidents.1 A less common, yet still devastating, complication is hemodynamically significant valvular and/or supravalvular aortic stenosis.2–4 It has been assumed that the intimal thickening of atherosclerosis resulted in luminal narrowing and compromised blood flow in the ascending aorta.1,5 We report 4 patients with supravalvular aortic stenosis in HFH in whom the decreased inner and outer diameters of the aorta were shown using ultrafast computed tomography. • • • Computerized tomography scans were performed using an Imatron C-100XL electron beam CT scanner (Imatron Corporation, Oyster Point, California). Images were generated using 3-mm contiguous sections from the aortic arch to below the heart. This was accomplished with 3 to 4 sets of 20 images each. Technical factors were 130 kV, 630 mA, and 100-ms duration; electrocardiographic gating to 80% of the RR interval was performed for every other heartbeat. All 4 patients had a markedly narrowed and calcified aortic root by ultrafast computed tomography, confirmed by other imaging studies. Because of progressive symptoms of aortic stenosis, 3 of the 4 patients have undergone surgery. Surgical procedures in these 3 patients required a specialized surgical approach because of the small size of the aortic root (Table I). Homozygous familial hypercholesterolemia is a rare disorder estimated at 1:1,000,000 births in the U.S. It is autosomal codominant in inheritance with variable penetrance. Because of a defect in the lowdensity lipoprotein receptor gene, elevation in levels of low-density lipoprotein particles result. Patients may develop stigmata of the disease at an early age such as arcus corneae and cutaneous xanthomas. But of more clinical importance is that they are subject to valvular and ischemic heart disease and to early atherosclerosis which has an affinity for the ascending aorta. The small circumference of the aortic root was described in early case reports based on the results of autopsy of patients for HFH and aortic valvular stenosis.2,3 In later reports the supravalvular stenosis was demonstrated by aortography.4 Echocardiography has also been used to diagnose and quantify supravalvular stenosis.6 Narrowing of the external diameter of the ascending aorta (measured from outside wall to outside wall) is readily apparent on cross-sectional imaging such as computerized tomography (Figure 1). The diminished size of the aorta would not be appreciated on aortography, which would demonstrate the luminal narrowing only and cannot differentiate luminal encroachment by plaque from hypoplasia of the aorta. Ultrafast computerized tomography is used to screen for and monitor calcium deposits in atherosclerotic lesions7 and can demonstrate decreased aortic caliber; similarly, magnetic resonance imaging can show both early intimal plaque and decreased aortic size. The narrowed aortic root appears to be due in part to the extensive atheromatous change involving the ascending aorta. However, there is some evidence that the degree of stenosis is disproportionately severe compared with the amount of intimal proliferation. This could be accounted for by hypoplasia of the aortic root. The normal growth of the vessel may be impaired due to perturbed hemodynamics or altered intercellular communication associated with atherosclerotic lesions in these young patients. In 3 of these cases, this impaired growth is manifested clinically during rapid growth in body mass during puberty. Detection of this lesion has profound clinical implications for these patients. If surgical procedures are under consideration for the aortic valve and/or supraFrom the Department of Radiology of the Clinical Center of the National Institutes of Health, Cardiology Branch, and Molecular Disease Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland; and Pediatric Cardiothoracic Surgery of the Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. Dr. Hoeg’s address is: Building 10, Room 7N115, 10 Center Drive MSC 1666, Bethesda, Maryland 20892-1666. Manuscript received July 28,1997; revised manuscript received and accepted January 28, 1998. TABLE I Clinical Data on Homozygous Familial Hypercholesterolemic Patients With Aortic Stenosis