DESCRIPTION 
- Supravalvular aortic stenosis (SVAS) may be caused rarely by a discrete membrane above the valve.
- The most common type is due to a defect in elastin, which causes aortic wall narrowing beginning at the sinotubular junction (the area just above the sinuses of Valsalva). In some patients, the narrowing is focal, causing a classic hourglass configuration. In others the ascending aorta is diffusely narrowed. Williams-Beuren syndrome (WBS) patients constitute the vast majority of these SVAS patients. Peripheral pulmonary artery stenosis is present in a majority of patients, along with characteristic physical appearance, mental retardation, and other organ system abnormalities.
- Rarely discrete supravalvular aortic stenosis is caused by a membrane above the valve with a small opening.
- Genetic counselling is appropriate in those with the familial autosomal dominant (nonsyndromic) disorder.
EPIDEMIOLOGY
Incidence
Reported incidences: 0.05% of congenital heart disease and 1/10,000 of people across all ethnic and racial groups.
Prevalence
Rare
RISK FACTORS
Genetics
- The majority of SVAS patients have WBS.
- Familial autosomal dominant and sporadic isolated cases also occur.
- Defect in elastin gene ELN on chromosome 7q11.23. The abnormality in WBS is a microdeletion and in the autosomal dominant and sporadic cases, a translocation.
PATHOPHYSIOLOGY
- In the most common form, a marked thickening of the aortic wall forms a constricting ridge at the sinotubular junction resulting in a so-called hourglass deformity.
- In other cases the thickening may cause diffuse narrowing of a variable length of the ascending aorta.
- Histologically there is disorganization and fragmentation of elastic fibers and an excess of vascular smooth muscle cells and collagen accumulation. The intima-media is thickened, and the arterial lumen of medium and large arteries is narrowed.
- The membranous type of SVAS results from a fibrous membrane stretched across the aortic lumen with a small central opening.
- Human and mouse studies have shown that elastin is required for terminal differentiation and quiescence of vascular smooth muscle cells.
- Elastin deficiency during development leads to hyperproliferation and hypertrophy of vascular smooth muscle cells, increased collagen accumulation, and wall thickening which tends to be inward.
- Elastin deficiency and fragmentation leads to loss of elasticity, distensibility, and normal recoil of the elastic arteries, likely a factor in the development of systemic HTN.
- Supravalvular (aortic) obstruction leads to LV hypertrophy.
- Pulmonary arterial narrowing leads to RV hypertrophy.
- Thickening of the supraaortic ridge may involve the coronary artery ostia, with resultant atypical coronary artery obstruction (nonatherosclerotic) and cause MI. Involvement of the valve cusp insertion has been reported to cause aortic insufficiency.
- High pressure in the aortic root below the level of obstruction subjects the coronary arteries to high systolic pressure, which may accelerate atherosclerosis. High pressure also causes accelerated degenerative change of the aortic valve cusps.
- Ventricular hypertrophy makes patients vulnerable to conditions of decreased preload such as dehydration or vasodilating agents.
ETIOLOGY
Genetic defect
COMMONLY ASSOCIATED CONDITIONS
- Peripheral pulmonary artery stenosis
- Williams-Beuren syndrome (WBS)
Outline
History
- WBS has classic features: Elfin faces (prominent forehead, epicanthal folds, hypertelorism, small upturned nose, and mandible) dental abnormalities, short stature, abnormalities in calcium metabolism, and mental retardation. Patients have specific cognitive disorders as well as anxiety, phobias, perseveration, and often a "cocktail party" personality (ie, they may be very sociable).
- Also associated with failure to thrive in infancy, GI hypomotility causing constipation and colic, and hyperacusis. Hypercalcemia and HTN are not uncommon, although the renal arteries are usually not involved in the arteriopathy.
- Adults with WBS often have HTN, urinary tract problems, and gastrointestinal abnormalities.
- The autosomal dominant and sporadic patients with SVAS have normal intelligence. They do not have the neighboring gene defects which cause the nonvascular manifestations of WBS.
Physical Exam
- There may be an increased aortic valve closure sound secondary to increased pressure proximal to the stenosis.
- A systolic ejection murmur is common along the left sternal border with thrill radiating to the suprasternal notch. A diastolic murmur component may be heard if the supravalvular stenosis distorts the valve architecture or has caused valve degeneration.
- BP is frequently higher in the right arm as opposed to the left arm due to preferential flow down the brachiocephalic vessels (Coanda effect).
- A continuous systolic murmur may be heard with associated pulmonary artery stenosis, if present.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
- ECG often shows signs of LV hypertrophy. Biventricular hypertrophy may be noted when pulmonary artery stenosis coexists.
- Fluorescent in situ hybridization FISH testing for the 7q11.23 deletion confirms the clinical diagnosis.
Imaging
- CXR:
- In contrast to both valvular and subvalvular aortic stenosis, ascending aortic dilation is rare on the chest radiograph.
- The sinuses of Valsalva may be dilated.
- Echo:
- Diagnostic tool of choice to identify the location and severity of the supravalvular aortic obstruction, as well as the presence and degree of ventricular hypertrophy.
- In SVAS, the sinuses of Valsalva are dilated relative to the size of the sinotubular junction.
- The location of the aortic outflow gradient can usually be identified and measured by Doppler.
- Dilation of the proximal pulmonary artery and RV hypertrophy in the absence of pulmonic valve stenosis suggest possible peripheral pulmonary arterial obstruction.
DIFFERENTIAL DIAGNOSIS
- Valvular aortic stenosis, subvalvular aortic obstruction, hypertrophic obstructive cardiomyopathy.
- A diffusely narrowed ascending aorta due to the elastin arteriopathy must be differentiated from hypoplastic left heart. In the latter, the aortic root and LV cavity are small/hypoplastic.
Outline
ADDITIONAL TREATMENT
General Measures
- Prophylaxis against bacterial endocarditis is not currently recommended in the absence of previous endocarditis.
- Echo should be performed if any change occurs in clinical findings or symptoms.
Pregnancy Considerations
- Severe SVAS may require repair prior to conception.
- Because of significant LV hypertrophy and outflow obstruction, dehydration and use of vasodilating agents should be avoided during pregnancy.
- If symptoms of CHF develop in the presence of SVAS, surgical repair may be indicated.
Referral
Because of the multisystem abnormalities, patients with WBS should be evaluated by a medical geneticist, and possibly a nephrologist and gastroenterologist, as well as a cardiologist for multidisciplinary assessment.
SURGERY
- Surgery should be considered if the patient is symptomatic, and has a significant gradient, and/or evidence of LVH with strain on EKG.
- Surgical repair of supravalvular aortic stenosis is less favorable than repair of valvular aortic stenosis.
- Aortotomy with excision of the fibrous obstruction is performed, often with a fabric prosthesis inserted into the area of the supravalvular narrowing to expand the lumen; sometimes complete root reconstruction is necessary.
- The diffuse tubular type may require replacement of the ascending aorta and proximal arch.
- Transcatheter balloon angioplasty is not an effective treatment for SVAS, but may be useful for treatment of peripheral pulmonary artery stenosis in patients undergoing SVAS surgery.
Outline
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Dependent on the severity of the hemodynamic abnormality:
- Severe obstruction should be monitored every 6–12 mo, and mild obstruction every 2–5 yr.
- A change in symptomatology demands immediate evaluation.
PATIENT EDUCATION
Activity:
- Patients with mild stenosis without symptoms may participate in full activities.
- Patients with moderate stenosis without symptoms may participate in low-impact activities.
- Patients with severe stenosis should not participate in vigorous activities.
PROGNOSIS
Depends on severity of arterial involvement. Long-term follow-up series have usually been in severely affected patients or those undergoing surgery. The peripheral pulmonary artery stenoses often do not require treatment and may improve with age.
COMPLICATIONS
Arterial HTN, LV hypertrophy, sudden death, endocarditis, secondary aortic valve disease.
Outline
CODES
ICD9
747.22 Congenital atresia and stenosis of aorta
SNOMED
7169009 congenital supravalvular aortic stenosis (disorder)