AHA/ACC Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease (2010)

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Commentary by Reed E. Pyeritz, MD, PhD

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Genetic syndromes

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Scientific evidence confirms that genetic alterations or mutations predispose some individuals to aortic diseases. Therefore, identification of the genetic alterations leading to these aortic diseases has the potential for early identification of individuals at risk.

Genetic SyndromeCommon Clinical FeaturesGenetic DefectDiagnostic TestComments on Aortic Disease
Marfan syndrome • Skeletal features (see text) • Ectopia lentis • Dural ectasiaFBNI mutations*• Ghent diagnostic criteria (2010) • DNA for sequencing • Surgical repair when the aorta reaches 5.0 cm unless there is a family history of AoD at <5.0 cm, a rapidly expanding aneurysm or presence or significant aortic valve regurgitation
Loeys-Dietz syndrome• Bifid uvula or cleft palate • Arterial tortuosity Hypertelorism • Skeletal features similar to Marfan • Craniosynostosis • Aneurysms and dissections of other arteriesTGFBR2 or TGFBR1 mutationsDNA for sequencing• Surgical repair recommended at an aortic diameter of ≥4.2 cm by TEE (internal diameter) or 4.4 to ≥4.6 cm by CT and/or MR (external diameter)
Ehlers-Danlos syndrome, vascular form• Thin, translucent skin • Gastrointestinal rupture • Rupture of the gravid uterus • Rupture of medium-sized to large arteriesCOL3A1 mutations• DNA for sequencing • Dermal fibroblasts for analysis of type III collagen• Surgical repair is complicated by friable tissues • Noninvasive imaging recommended
Turner syndrome• Short stature • Primary amenorrhea • Bicuspid aortic valve • Aortic coarctation • Webbed neck, low-set ears, low hairline, broad chest45,X karyotypeBlood (cells) for karyotypeanalysis• AoD risk is increased in patients with bicuspid aortic • Valve, aortic coarctation, hypertension, or pregnancy
* The defective gene at a second locus for Marfan is TGFBR2 but the clinical phenotype as Marfan is debated. AoD indicates aortic dissection; COL3A1, type III collagen; CT, computed tomographic imaging; FBN1, fibrillin 1; MR, magnetic resonance imaging; TEE, transesophageal echocardiogram; TGFBR1, transforming growth factor-beta receptor type I; and TGFBR2, transforming growth factor-beta receptor type II.

Recommendations for management

Class I1. An echocardiogram is recommended at the time of diagnosis of Marfan syndrome to determine the aortic root and ascending aortic diameters and 6 months thereafter to determine the rate of enlargement of the aorta. (LOE: C) 2. Annual imaging is recommended for patients with Marfan syndrome if stability of the aortic diameter is documented. If the maximal aortic diameter is 4.5 cm or greater, or if the aortic diameter shows significant growth from baseline, more frequent imaging should be considered. (LOE: C) 3. Patients with Loeys-Dietz syndrome or a confirmed genetic mutation known to predispose to aortic aneurysms and aortic dissections (TGFBR1, TGFBR2, FBN1, ACTA2, or MYH11) should undergo complete aortic imaging at initial diagnosis and 6 months thereafter to establish if enlargement is occurring. (LOE: C) 4. Patients with Loeys-Dietz syndrome should have yearly magnetic resonance imaging from the cerebrovascular circulation to the pelvis. (LOE: B) 5. Patients with Turner syndrome should undergo imaging of the heart and aorta for evidence of bicuspid aortic valve, coarctation of the aorta, or dilatation of the ascending thoracic aorta. If initial imaging is normal and there are no risk factors for aortic dissection, repeat imaging should be performed every 5 to 10 years or if otherwise clinically indicated. If abnormalities exist, annual imaging or follow-up imaging should be done. (LOE: C)
Class IIa1. It is reasonable to consider surgical repair of the aorta in all adult patients with Loeys-Dietz syndrome or a confirmed TGFBR1 or TGFBR2 mutation and an aortic diameter of 4.2 cm or greater by transesophageal echocardiogram (internal diameter) or 4.4 to 4.6 cm or greater by computed tomographic imaging and/or magnetic resonance imaging (external diameter). (LOE: C) 2. For women with Marfan syndrome contemplating pregnancy, it is reasonable to prophylactically replace the aortic root and ascending aorta if the diameter exceeds 4.0 cm. (LOE: C) 3. If the maximal cross-sectional area in square centimeters of the ascending aorta or root divided by the patient’s height in meters exceeds a ratio of 10, surgical repair is reasonable because shorter patients have dissection at a smaller size and 15% of patients with Marfan syndrome have dissection at a size smaller than 5.0 cm. (LOE: C)
Class IIb2. In patients with Turner syndrome with additional risk factors, including bicuspid aortic valve, coarctation of the aorta, and/or hypertension, and in patients who attempt to become pregnant or who become pregnant, it may be reasonable to perform imaging of the heart and aorta to help determine the risk of aortic dissection. (LOE: C)