Supravalvular Aortic Stenosis

Supravalvular aortic stenosis (SVAS) is a fixed narrowing of the ascending aorta that starts at the sinotubular junction. It takes three forms: a localised hourglass narrowing (the most frequent), a discrete fibrous membrane, and diffuse hypoplasia of the ascending aorta that may extend into the arch and its branches.

The cause is loss of function of the elastin gene (ELN, chromosome 7q11.23). This occurs either as an isolated autosomal dominant mutation with variable penetrance, or as part of the contiguous deletion of Williams-Beuren syndrome (about 1 in 7,500 to 10,000 live births), in which about half or more of patients have SVAS.

Associated lesions are peripheral and supravalvular pulmonary stenosis, renal artery and mid-aortic narrowing, mitral valve prolapse and bicuspid aortic valve.

Pathophysiology. Elastin deficiency produces a thickened media with smooth muscle hyperplasia, disorganised elastic lamellae and intimal thickening, so the vessel is stiff and narrow. The fixed obstruction causes concentric left ventricular hypertrophy.

Because the narrowing lies distal to the valve, the coronary ostia sit in the high pressure zone. The coronary arteries become dilated and tortuous, and the aortic leaflets can tether to the narrowed ridge and obstruct ostial flow.

Coronary perfusion depends on diastolic pressure and falls with tachycardia, hypovolaemia and vasodilatation. The consequences are subendocardial ischaemia, ventricular arrhythmia and sudden death, especially during anaesthesia or sedation in Williams-Beuren syndrome.

The stenotic jet is directed towards the innominate artery (Coanda effect), so right arm systolic pressure exceeds left arm pressure by 10 mm Hg or more.

• Isolated SVAS: a murmur found in childhood; exertional dyspnoea, angina, presyncope or syncope when obstruction is severe; sudden death.
• Williams-Beuren syndrome: periorbital fullness, short nose with a bulbous tip, long philtrum, wide mouth and full lips; infantile hypercalcaemia in about 15%; hoarse voice; hyperacusis; mild to moderate intellectual disability with a hypersocial manner and anxiety; short stature; joint laxity then contractures; hypertension; hypothyroidism; renal anomalies; diverticular disease and impaired glucose tolerance in adults.
• Examination: ejection systolic murmur loudest at the right upper sternal edge, radiating to the neck with a carotid thrill; no ejection click; right arm systolic pressure higher than left by 10 mm Hg or more; additional murmurs over the back and axillae from peripheral pulmonary stenosis.

Red flags.

• Exertional syncope, angina or dyspnoea
• ST depression on ECG or ventricular arrhythmia
• Bilateral (left and right) outflow obstruction in Williams-Beuren syndrome
• Coronary ostial involvement
• Planned anaesthesia, sedation or catheterisation in Williams-Beuren syndrome
• Rising gradient or severe left ventricular hypertrophy
• New or severe hypertension (renal artery stenosis)

• ECG: left ventricular hypertrophy with strain; right ventricular hypertrophy when pulmonary stenosis coexists.
• Echocardiography: parasternal long axis and suprasternal views show the narrowing at the sinotubular junction. Measure its diameter (as a Z-score), the continuous wave Doppler peak and mean gradient, left ventricular wall thickness, aortic leaflet mobility, left main stem flow on colour Doppler, arch branch vessels and pulmonary artery branches.
• CT or MR angiography: the whole aorta and its branches, coronary ostia, renal arteries and pulmonary arteries.
• Cardiac catheterisation with coronary angiography: for suspected ostial disease or when gradients are discordant. It carries a high risk of arrest in Williams-Beuren syndrome and is done only in a centre with congenital cardiac anaesthesia and mechanical circulatory support available.
• Genetic testing: chromosomal microarray or FISH for the 7q11.23 deletion; ELN sequencing when no deletion is found.
• Other tests: serum calcium (infancy and when symptomatic), creatinine, thyroid function, glucose in adults; renal ultrasound; blood pressure in all four limbs.

Differential diagnosis.

• Valvar aortic stenosis (bicuspid or dysplastic valve with an ejection click)
• Subaortic stenosis
• Hypertrophic obstructive cardiomyopathy
• Coarctation or mid-aortic syndrome
• Peripheral pulmonary artery stenosis from other causes (Alagille syndrome, Noonan syndrome, congenital rubella)
• Takayasu arteritis
• Homozygous familial hypercholesterolaemia with xanthomatous aortic root disease
• Atherosclerotic coronary disease in adults

• Medical therapy. No drug relieves the obstruction. Avoid dehydration, hypovolaemia, prolonged fasting, tachycardia and agents that lower diastolic pressure. Beta blockers are used cautiously for angina or ventricular ectopy. In hypertension, first exclude renal artery stenosis by duplex or CT or MR angiography, then start low dose therapy.
• Indications for surgery: symptoms attributable to the obstruction, ischaemia, left ventricular dysfunction, or a peak Doppler gradient of 50 mm Hg or more (mean 30 mm Hg or more) with left ventricular hypertrophy. Surgery is considered at lower gradients with coronary ostial involvement, before pregnancy, and before competitive sport.
• Operation: patch augmentation of the aortic root and ascending aorta (single patch repair into the non-coronary sinus, or three patch repair of all three sinuses) with enlargement of any stenotic coronary ostium and release of tethered leaflets. Diffuse arch disease needs extended patch repair. Balloon angioplasty and stenting do not relieve the aortic lesion. Reoperation for recurrent obstruction is needed in a minority.
• Anaesthesia or sedation in Williams-Beuren syndrome: cardiac arrest risk is many times that of the general population. Use a congenital cardiac anaesthesia team, maintain preload with intravenous fluids during fasting, avoid hypotension, tachycardia and hypovolaemia, place defibrillator pads before induction, and have mechanical circulatory support available for high risk patients.
• Peripheral pulmonary stenosis: often improves in infancy; catheter balloon angioplasty or stenting for significant right ventricular hypertension.
• Infantile hypercalcaemia: stop calcium and vitamin D supplements, give low calcium formula, ensure hydration, and check calcium weekly until normal. Refractory cases need specialist treatment.
• Endocarditis prophylaxis: only for prosthetic material, previous endocarditis or unrepaired cyanotic disease.

Special groups.

• Williams-Beuren syndrome: lifelong surveillance for hypertension, renal artery stenosis, hypercalcaemia, hypothyroidism and diabetes.
• Pregnancy: tolerated with mild obstruction and normal ventricular function. With symptoms or a peak gradient of 50 mm Hg or more, repair before conception.

Monitoring. Echocardiography every 6 to 12 months in children and every 1 to 2 years in stable adults, shortened when the gradient rises. Four limb blood pressure and renal duplex at diagnosis and when hypertension appears. Exercise testing before sport. After repair, CT or MR angiography of the aortic root, arch and coronary ostia at 6 to 12 months, then every 2 to 3 years.

Referral and escalation. Refer to a congenital heart disease centre at diagnosis. Urgent for syncope, angina, ischaemic ECG changes or any planned anaesthesia, sedation or catheterisation in Williams-Beuren syndrome.