Pediatric Supravalvar Aortic Stenosis

Supravalvar aortic stenosis (SVAS) is a fixed form of congenital left ventricular outflow tract (LVOT) obstruction that occurs as a localized or diffuse narrowing of the ascending aorta beyond the superior margin of the sinuses of Valsalva.[1] It accounts for less than 7% of all fixed forms of congenital LVOT obstructive lesions. SVAS is demonstrated in the images below.[2]

SVAS may occur sporadically, as a manifestation of elastin arteriopathy, or as part of Williams syndrome (also known as Williams-Beuren syndrome), an autosomal dominant genetic disorder. The sporadic form of SVAS is the most common (>50%) presentation. There is no known risk factor to account for these cases. (See Epidemiology and Etiology.)

A less common presentation of SVAS is a familial form caused by autosomal dominant inheritance. Like the sporadic form, it is not a part of Williams syndrome.

Patients with SVAS are usually asymptomatic, but cases associated with Williams syndrome are usually identified during infancy. The diagnosis of Williams syndrome can be established with cytogenic analysis, which means that this diagnosis can be made in utero using chorionic villus tissue. Therefore, SVAS can be detected prenatally, particularly in patients with Williams syndrome, if it is revealed with fetal echocardiography. (See Workup.)

The anatomic diagnosis of SVAS can reliably be made from 2-dimensional (2D) echocardiography that uses multiple views, including parasternal, apical long-axis, and suprasternal (see Workup). Cardiac catheterization or MRI may be indicated to evaluate the coronary artery or aortic arch anatomy. Surgery is the primary treatment for SVAS. The choice of procedure varies with the type and severity of the stenosis. (See Treatment.)

Go to Aortic Stenosis for more complete information on this topic.

Supravalvar aortic stenosis (SVAS) has three commonly recognized morphologic forms. An external hourglass deformity of the aorta with a corresponding luminal narrowing at a level just distal to the coronary artery ostia is present in 50-75% of patients.[3] In approximately 25% of patients, a fibrous diaphragm is present just distal to the coronary artery ostia. In fewer than 25% of patients, a diffuse narrowing along a variable length of ascending aorta is present.

Similarly, the following three anatomic subtypes of coronary lesions have been recognized in SVAS[4] :

• Circumferential narrowing of the left coronary ostium

• Ostial obstruction due to fusion of the aortic cusp to the supravalvar ridge

• Diffuse narrowing of the left coronary artery

The origins of the coronary arteries proximal to the obstruction site have the same systolic pressure as the left ventricle (LV), which is abnormally elevated based on the severity of obstruction.[3] Consequently, they become dilated and tortuous over time, with hypertrophy and intimal thickening. These changes predispose them to premature atherosclerosis. The hemodynamic consequences of coronary artery changes are increased total mean coronary flow but significantly decreased diastolic coronary flow, which is the major determinant of the development of myocardial ischemia.

Concentric LV hypertrophy caused by supravalvar aortic stenosis (SVAS) exacerbates the problem of myocardial ischemia. In most patients, the jet of blood flow from SVAS has a preferential trajectory into the brachiocephalic vessels, the so-called Coanda effect[5] ; this accounts for a marked increase in the right upper extremity systolic pressure relative to the left.

Complications of SVAS also include progressive coronary osteal stenosis, infective endocarditis, and sudden death.[6]

The precise etiology of supravalvar aortic stenosis (SVAS) is unknown. The disease’s high association with Williams syndrome, a genetic disorder caused by a hemizygous deletion or mutation of the elastin gene at band 7q11,[7] suggests that defective connective tissue formation contributes to its pathology.

Patients with the sporadic form of SVAS may have associated peripheral pulmonary artery stenosis. There is no known risk factor for sporadic SVAS.

As previously stated, a less common presentation of SVAS is a familial form caused by autosomal dominant inheritance.

The crude incidence of congenital heart defects is approximately 8 cases per 1000 live births. SVAS accounts for less than 0.05% of congenital heart defects. The sporadic form of SVAS is more common than the autosomal dominant form.[8]

As previously mentioned, the sporadic form of SVAS is the most common (>50%) presentation.

In one series, the actuarial survival rate following operative repair of supravalvar aortic stenosis (SVAS) was approximately 85% at 15 years. Overall survival, including operative mortality, was 98% at 10 years and 97% at 20 years and at 30 years.[9]

Postoperatively in this study, 73% of patients were in class I of the New York Heart Association's (NYHA) functional classification, and 27% were in NYHA functional class II.[9] Most patients did not require reoperation.

Prognosis is influenced by the presence of genetic disorders, coronary artery lesions, and associated obstructive lesions of pulmonary arteries.[10] SVAS is a progressive lesion, whereas peripheral pulmonary artery stenosis remains unchanged or decreases in severity over time.[11] The mortality rate is higher in patients with diffuse SVAS than in those with the localized form.

The risk of sudden cardiac death, including in patients who have undergone surgery, is 1 case per 1000 patient years and is 25-100 times higher than in the normal population.[12] Patients with SVAS are vulnerable to cardiac arrest or significant hemodynamic instability during induction of anesthesia secondary to hypotension and decreased coronary artery perfusion.

Anatomic abnormalities that predispose individuals with SVAS and Williams syndrome to sudden death include coronary artery stenosis and severe biventricular outflow tract obstruction. The mechanisms for sudden death for both anatomic subgroups are believed to include myocardial ischemia, decreased cardiac output, and arrhythmia.[13]

Preoperative recommendations for restriction of physical activities should be followed (see Activity). Physical activity restrictions are not required postoperatively if no residual lesion is present (including coronary artery involvement) and the pressure gradient is less than 20 mm Hg across the LVOT, which is similar to the preoperative recommendation.

In general, persons with SVAS should have risk stratification for coronary artery disease early in adult life, because SVAS may predispose the coronary artery to premature atherosclerotic changes.

Symptoms caused by supravalvar aortic stenosis (SVAS) usually develop in childhood. Rarely, symptoms may develop in infancy; in some cases, symptoms develop in the second or third decade of life.

Most pediatric patients present because of a heart murmur or the features of Williams syndrome. Patients with Williams syndrome may also develop systemic hypertension and involvement of joints, peripheral pulmonary artery stenosis, coarctation of aorta, and mitral insufficiency.[14]

Dyspnea on exertion, angina, and syncope develop in the course of the disease if SVAS is untreated. These symptoms indicate at least a moderate degree of left ventricular outflow tract (LVOT) obstruction. Because of the coronary artery involvement, angina may arise early and more often than in other obstructive LVOT lesions. Because of the risk of sudden death in SVAS, the development of angina and syncope should prompt immediate investigation.

The physical examination focuses on upper extremity pulses, the precordium, heart sounds, and heart murmurs.

Asymmetrical upper extremities pulses

Discrepancies between carotid pulsations and upper extremity pulses and blood pressure are the characteristic clinical findings in supravalvar aortic stenosis (SVAS) . The discrepancies occur because the jet of blood flow from SVAS has a preferential trajectory into the brachiocephalic (innominate) artery (ie, Coanda effect).

Precordium

The precordium is usually hyperdynamic, and the apex of the heart is displaced laterally and inferiorly because of ventricular hypertrophy. A thrill in the suprasternal notch is usually felt because of the trajectory of the blood flow jet from SVAS.

Heart sounds

The first heart sound is generally normal. A narrowly split, single, or paradoxically split second heart sound and a fourth heart sound are present in severe SVAS.

Heart murmurs

The characteristic systolic murmur of SVAS is crescendo-decrescendo in shape, low pitched, and best heard at the base of the heart, sited higher than in valvular aortic stenosis. It mainly radiates to the right carotid artery and tends to peak during the last two thirds of ventricular systole if the obstruction is severe.

A high-pitched, short, early diastolic aortic regurgitation murmur is uncommon in SVAS unless the aortic valve has become damaged due to the supravalvar obstruction and has become regurgitant.  An ejection click is absent.

Supravalvar aortic stenosis (SVAS) produces abnormalities that are evident on electrocardiography (ECG) and chest radiography. These include increased left ventricular voltages from left ventricular hypertrophy. ST and T wave changes may be present if there is coronary involvement. Additionally, if right ventricular outflow tract obstruction is present, there may be voltage criteria for right ventricular hypertrophy. Chest radiography is of low sensitivity, although the cardiac silhouette may be variably increased and the ascending aorta may be asymmetrically dilated. The presence of both findings indicates hemodynamically significant SVAS.

The principal diagnostic test, however, is two-dimensional echocardiography. Cardiac catheterization along with angiography may be performed at an increased risk as indicated, but it may be necessary to evaluate the severity of the lesion and to confirm the coexisting anomalies prior to surgery if they cannot be accurately assessed with other modalities. Magnetic resonance imaging (MRI) may be utilized to evaluate for stenosis of the arch vessels or for better delineation of the anatomy if cardiac catheterization is not performed.

Go to Imaging in Aortic Stenosis for more complete information on this topic.

The anatomic diagnosis of supravalvar aortic stenosis (SVAS) can reliably be made from two-dimensional echocardiography that uses multiple views, including parasternal, apical long-axis, and suprasternal (seen in the image below).

In SVAS with hourglass deformity and diffuse hypoplasia, the diameter of the ascending aorta is smaller than that of the aortic root. In SVAS with fibrous diaphragm, the external ascending aortic diameter is normal, although an echogenic membrane is commonly observed above the sinuses of Valsalva.

Turbulent color flow mapping indicates the site of hemodynamically significant obstruction in relation to the origin of the coronary ostia. The incidence of coronary artery involvement is high in SVAS.[16]

Doppler peak gradient overestimates and, therefore, does not predict catheter-measured gradient well in patients with SVAS and may not be reliable in assessing its severity and guiding the need for intervention.[17]

A retrograde aortic catheterization with an end-hole catheter can be used to localize the site of obstruction by showing the pressure gradient above the aortic valve on pullback tracing. Cutting balloon angioplasty and endovascular stenting have been utilized with variable success for associated peripheral pulmonary artery stenosis when conventional balloon angioplasty fails.[18]

Complications include blood vessel rupture, tachyarrhythmias, bradyarrhythmias, and vascular occlusion. Postcatheterization precautions are for hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm.

Cardiac asystole and mortality due to coronary events have been reported during catheterization and during the postprocedure period. Cardiac catheterization should therefore be performed only if clearly indicated. General anesthesia should be undertaken with close supervision and by an experienced anesthesiologist. Any form of anesthesia should avoid hypotension or a decrease in systemic vascular resistance which may precipitate coronary artery ischemia.

ECG usually reveals left ventricular hypertrophy, depending on the severity of stenosis. ST/T segment changes may be present with involvement of coronary ostia and the coronary arteries. Right ventricular hypertrophy may be present if there is associated right ventricular outflow tract obstruction.

A biplane left ventriculogram and an aortogram can reveal the morphology of supravalvar narrowing, stenosis of the arch vessels, aortic root abnormalities, and location of the coronary artery ostia in relation to the site of supravalvar obstruction (see the image below). The coronary arteries may or may not appear abnormal. Right ventricular or pulmonary arterial angiography should be performed simultaneously in order to discern the presence of peripheral pulmonary artery stenosis, particularly in Williams syndrome.

Although magnetic resonance imaging (MRI) can provide high definition of supravalvar aortic stenosis (SVAS), obtaining an MRI in infants and young children may require sedation, which carries a risk of sudden death. Therefore, this study should be undertaken with close supervision and administered by an experienced anesthesiologist. MRI may be particularly useful in delineating aortic arch anatomy and evaluating for stenosis of the arch vessels.

Multislice computed tomography (CT) scanning with angiography can generate high-resolution images of aortic valve lesions within seconds. However, this test exposes the pediatric patient to radiation, although it can now be performed without sedation (ultrafast flash CT).

Myocardial hypertrophy, coronary intimal hyperplasia, and atherosclerotic changes can be observed in most cases of supravalvar aortic stenosis (SVAS). Subendocardial fibrosis may be present in severe cases of SVAS. Abnormal deposition of elastin in arterial walls of patients with SVAS has been seen, which leads to the increased proliferation of arterial smooth muscle cells, resulting in the formation of hyperplastic intimal lesions.[19]

Obtain a genetic evaluation for patients with SVAS to confirm the diagnosis of Williams syndrome, which is often associated with SVAS. Molecular diagnosis of Williams syndrome can be made by fluorescent in situ hybridization (FISH) using Williams probe.

Surgery is the primary treatment for supravalvar aortic stenosis (SVAS). Children and adolescents with catheter peak-to-peak (or Doppler mean) gradient of 50 mm Hg or more should have surgical intervention. The choice of procedures in these patients is similar to that indicated for valvar aortic stenosis.[20]

Children and adolescents with catheter peak-to-peak (or Doppler mean) gradient of 30-50 mm Hg may be considered for surgical intervention if they are symptomatic, with angina, syncope, or dyspnea on exertion (class I). Asymptomatic patients who have developed ST/T-wave changes over the left precordium on ECG at rest or with exercise should also be considered for surgical intervention (class I). Aortic valve involvement and lower supravalvar gradients may also warrant surgical intervention.

Surgical resection of the supravalvar obstruction and patch aortoplasty and multiple-sinus reconstructions (inverted bifurcated patch plasty and 3-sinus reconstruction) are the procedures of choice for the fibrous diaphragm and hourglass deformities.[21]

Associated coronary artery involvement is addressed with the following measures, which are performed at the same time as aortoplasty:

• Patch aortoplasty encompassing the left main ostium for circumferential narrowing of the left main ostium

• Excision of the fused leaflet from the aortic wall for ostial obstruction caused by a fusion of the aortic cusp to the supravalvar ridge[22]

• Bypass grafting for diffuse narrowing of the left main coronary artery

In patients who have SVAS with diffuse narrowing, the ascending aorta and the arch of the aorta can be reconstructed using an aortic allograft or a pulmonary autograft.

Surgical treatment of associated abnormalities of aortic valve and aortic arch vessels should be undertaken at the same time to optimize the overall surgical outcome.[23]

Standard postoperative care and precautions for pediatric cardiac patients are also required for patients with SVAS. Postoperative complications include aortic insufficiency (in 25% of patients).

Activity restrictions may be indicated, depending on the severity of the disorder. Exercise recommendations for children with SVAS and no coronary artery involvement are as follows:

• Mild stenosis (< 20 mm Hg), normal ECG findings, no symptoms - Full sports participation

• Moderate stenosis (21-49 mm Hg), mild left ventricular hypertrophy (LVH), no symptoms - Low static or moderately dynamic sports participation

• Severe stenosis (>50 mm Hg) or moderate degree of stenosis with symptoms - No competitive sports participation (at most recreational)

• Coronary artery stenosis or abnormal anatomy - No competitive sports participation (at most recreational and dependent on the level of obstruction)

Williams syndrome, which is found in many children with supravalvar aortic stenosis (SVAS), may be associated with infantile hypercalcemia with some risk of nephrocalcinosis, osteosclerosis with progressive joint limitation and abnormal gait, and neurodevelopmental delay. These children require multidisciplinary support. Use a coordinated management approach. They are also at risk of higher mortality than the normal population is, because of cardiac and noncardiac causes.

No published reports have documented the outcome of pregnancy in postoperative patients with SVAS. Address pregnancy on an individual basis, taking into account the type of lesion and surgical procedure performed, the presence of residual lesion, and the associated cardiac and noncardiac conditions and syndromes.

Follow-up care is recommended for all patients with SVAS, whether or not their condition has been surgically corrected, and the frequency is based on the severity of the obstruction and whether there is coronary artery involvement. Rapid progression of SVAS may occur preoperatively.

Detailed cardiac examination and echocardiography should be performed at the follow-up visit. Changes in intensity of the murmur may indicate progressive stenosis; the development of ST-segment or T-wave changes may signal coronary involvement.

Consult a pediatric cardiologist and a pediatric cardiac surgeon, as needed.

Aortic valvuloplasty

In 2011, the American Heart Association (AHA) released guidelines for interventions in pediatric cardiac disease that included the following class I recommended indications for aortic valvuloplasty in children[20] :

• In newborns with isolated critical valvar aortic stenosis (AS) who are ductal dependent regardless of valve gradient
• In children with isolated valvar AS who have the following characteristics:

  • Depressed left ventricular systolic function
  • ​Resting peak systolic valve gradient (by catheter) of ≥50 mm Hg
  • Resting peak systolic valve gradient (by catheter) of ≥40 mm Hg in the presence of anginal or syncopal symptoms or ischemic ST-T-wave changes on electrocardiography at rest or with exercise

According to these guidelines, aortic valvuloplasty may be considered in an asymptomatic child or adolescent with a resting peak systolic valve gradient (by catheter) of ≥40 mm Hg or without ST–T-wave changes if pregnancy or participation in strenuous competitive sports is desired (class IIb).

Aortic valve balloon dilation is not indicated in children with isolated valvar AS who also have a degree of aortic regurgitation that warrants surgical aortic valve replacement or repair (class III).

Transcatheter aortic valve replacement (TAVR)

In 2017, the AHA/American College of Cardiology released a focused update of their 2014 guidelines for managing patients with valvular heart disease, including their TAVR recommendations, which are summarized below.[24, 25]

Anticoagulation with a vitamin K antagonist (VKA) is indicated for patients with rheumatic mitral stenosis (MS) and atrial fibrillation (AF).

Anticoagulation is indicated in patients with AF and a CHA2DS2-VASc score of 2 or greater with native aortic valve disease, tricuspid valve disease, or mitral regurgitation (MR).

Surgical aortic valve replacement is recommended for symptomatic patients with severe AS (stage D) and asymptomatic patients with severe AS (stage C) who meet an indication for AVR when surgical risk is low or intermediate.

TAVR is recommended for symptomatic patients with severe AS (stage D) and a prohibitive risk for surgical AVR who have a predicted post-TAVR survival greater than 12 months.

Mitral valve surgery is recommended for symptomatic patients with chronic severe primary MR (stage D) and left ventricular ejection fraction (LVEF) greater than 30%.

Mitral valve surgery is recommended for asymptomatic patients with chronic severe primary MR and LV dysfunction (LVEF 30%-60% and/or LV end-systolic diameter [LVESD] ≥40 mm, stage C2).

Mitral valve repair is recommended in preference to mitral valve replacement (MVR) when surgical treatment is indicated for patients with chronic severe primary MR limited to the posterior leaflet.

A bioprosthesis is recommended in patients of any age for whom anticoagulant therapy is contraindicated, cannot be managed appropriately, or is not desired.

Anticoagulation with a VKA and international normalized ratio (INR) monitoring is recommended in patients with a mechanical prosthetic valve.

Anticoagulation with a VKA to achieve an INR of 2.5 is recommended for patients with a mechanical bileaflet or current-generation single-tilting disc AVR and no risk factors for thromboembolism.

Anticoagulation with a VKA is indicated to achieve an INR of 3.0 in patients with a mechanical AVR and additional risk factors for thromboembolic events (AF, previous thromboembolism, LV dysfunction, or hypercoagulable conditions) or an older-generation mechanical AVR (such as ball-in-cage).

Anticoagulation with a VKA is indicated to achieve an INR of 3.0 in patients with a mechanical MVR.

Aspirin 75-100 mg daily is recommended in addition to anticoagulation with a VKA in patients with a mechanical valve prosthesis.

Continuation of VKA anticoagulation with a therapeutic INR is recommended in patients with mechanical heart valves undergoing minor procedures (eg, dental extractions or cataract removal) where bleeding is easily controlled.

Temporary interruption of VKA anticoagulation, without bridging agents while the INR is subtherapeutic, is recommended in patients with a bileaflet mechanical AVR and no other risk factors for thrombosis who are undergoing invasive or surgical procedures.

Urgent evaluation with multimodality imaging is indicated in patients with suspected mechanical prosthetic valve thrombosis to assess valvular function, leaflet motion, and the presence and extent of thrombus.

Urgent initial treatment with either slow-infusion low-dose fibrinolytic therapy or emergency surgery is recommended for patients with a thrombosed left-sided mechanical prosthetic heart valve presenting with symptoms of valve obstruction.

Repeat valve replacement is indicated for severe symptomatic prosthetic valve stenosis.

Surgery is recommended for operable patients with mechanical heart valves with intractable hemolysis or heart failure (HF) due to severe prosthetic or paraprosthetic regurgitation.

Early surgery (during initial hospitalization before completion of a full therapeutic course of antibiotics) is indicated in patients with infective endocarditis (IE) who present with valve dysfunction resulting in symptoms of HF.

Early surgery (during initial hospitalization before completion of a full therapeutic course of antibiotics) is indicated in patients with IE who present with valve dysfunction resulting in symptoms of HF.

Early surgery is indicated in patients with left-sided IE caused by S aureus, fungal, or other highly resistant organisms.

Early surgery is indicated in patients with IE complicated by heart block, annular or aortic abscess, or destructive penetrating lesions.

Infective endocarditis prophylaxis

The 2011 AHA guidelines defined the following patient groups as at highest risk for adverse outcomes from IE[20] :

• Those with prosthetic cardiac valves or prosthetic material used for cardiac valve repair
• Those with previous IE
• Those with unrepaired cyanotic congenital heart disease (CHD), including palliative shunts and conduits
• Those with CHD and completely repaired congenital heart defect that was repaired with prosthetic material or device, regardless of placement by surgery or catheter intervention, during the first 6 months after the procedure
• Those with repaired CHD who have residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device
• Recipients of cardiac transplantation who develop cardiac valvulopathy

In a 2015 scientific statement updating its recommendations on IE in childhood, the AHA advocated for a shift in focus from antibiotic prophylaxis to an emphasis on oral hygiene and prevention of oral disease. However, the AHA recommends considering prophylactic antibiotic drugs before certain dental procedures for children in the highest-risk groups (class IIb), such as those discussed above.[26]

Surgery is the primary treatment for SVAS.