Continuing Education Activity

Subvalvular aortic stenosis (SAS), also called subaortic stenosis, is a rare disorder seen in infants. In most cases, it involves the presence of a membrane that is typically muscular just below the aortic valve, which causes a fixed obstruction to blood flow across the left ventricular outflow tract. The course of subvalvular aortic stenosis is gradual and patients rarely present with isolated symptoms. SAS may co-occur with a ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, bicuspid aortic valve, abnormal left ventricular papillary muscle, and/or atrioventricular septal defect, among others. In the majority of the patients, SAS is incidentally found when evaluating patients for other congenital heart defects. This activity describes the evaluation, diagnosis, and management of subvalvular aortic stenosis and highlights the role of team-based interprofessional care for affected patients.

Objectives:

• Explain the pathophysiologic basis of subvalvular aortic stenosis.
• Describe the details pertinent to the evaluation of infants with congenital heart defects.
• Outline the treatment strategy for an infant with subvalvular aortic stenosis.
• Demonstrate interprofessional team strategies for improving care coordination and communication to enhance outcomes for patients affected by subvalvular aortic stenosis.

Introduction

Subvalvular aortic stenosis (SAS), also called subaortic stenosis, is a rare disorder seen in infants. In most cases, there is a membrane (usually muscular) just below the aortic valve which causes a fixed obstruction to the blood flow across the left ventricular outflow tract. Despite being classified as a congenital heart defect, the fact that it is rare at birth and infancy, its gradual course and its high rate of postoperative recurrence propose that it may be an acquired defect.

Anatomy

The anterior leaflet of the mitral valve along with the intravalvular fibrosa form the posterolateral border and the muscular and membranous portions of the intraventricular septum form the anteromedial borders of the left ventricular outflow tract.

Anatomic Variants

There is a spectrum of variants of subvalvular aortic stenosis that occurs alone or in combination with the others. These are as follows:

1. A thin discrete membrane: The most common lesion
2. A fibromuscular ridge 
3. A diffuse fibromuscular tunnel-like narrowing of the left ventricular outflow tract  (LVOT)[1],[2]
4. Accessory or anomalous mitral valve tissue

In most patients, membrane attached to the ventricular septum or encompassing the left ventricular outflow tract causes the obstruction.[3],[4],[5]. Its position is anywhere from immediately below the aortic valve to further down into the left ventricle. The base of the aortic valve leaflets is noted to be involved by this subaortic tissue thus restricting the mobility and adding to the left ventricular outflow tract.

Natural History

As mentioned previously, the course of subvalvular aortic stenosis is gradual. It is rarely an isolated presentation. SAS is associated with congenital heart defects including a ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, bicuspid aortic valve, abnormal left ventricular papillary muscle, atrioventricular septal defect, among others. In the majority of the patients, SAS is incidentally found when evaluating patients for other congenital heart defects.

Etiology

Many mechanisms contribute to the development of fixed subvalvular aortic stenosis, for example, genetic factors, hemodynamic abnormalities seen in other cardiac lesions, or underlying left ventricular outflow tract morphology that increases the turbulence at the outflow tract.[6] A narrow LVOT, exaggerated aortic override, increased mitral-aortic septation, and steep atrioventricular septal angle may result in a chronic flow disturbance. These factors increase the fluid shear stress on the interventricular septum and induce an abnormal endothelial and muscle proliferation resulting in the formation of a fibromuscular ridge. This may account for the development of subvalvular aortic stenosis. The repair of associated congenital heart defects may modify the left-sided outflow increasing the turbulence and fluid shear stress on the interventricular septum contributing to the development of subvalvular aortic stenosis.

Epidemiology

Subvalvular aortic stenosis is a rare disorder seen in infants and newborns but is the second most common type of aortic stenosis. It is responsible for approximately 1% of all congenital heart defects (8 in 10,000 births) and 15% to 20% of all fixed left ventricular outflow tract obstructive lesions.

Ten percent to 14% of subvalvar aortic stenosis is observed amongst children with congenital aortic stenosis.[7],[8] It is more common in males and is responsible for 65% to 75% of the cases.[7],[8] with a male to female ratio of 2:1. The prevalence of SAS is 6.5% of all the adult congenital heart diseases.[9]

SAS is associated with other cardiac malformations in 50% to 65% of cases [10],[3],[11]. In a report of 35 patients, associated lesions were found.

• Ventricular septal defect (VSD) (20%)
• Patent ductus arteriosus (34%)
• Pulmonic stenosis (9%)
• Aortic coarctation (23%)
• Miscellaneous other lesions (14%)

Pathophysiology

Subvalvular aortic stenosis causes clinically significant obstruction to the blood flow ejecting out of the left ventricle resulting in the development of concentric left ventricular hypertrophy, frequently with a septal bulge. This, in turn, results in the further obstruction and hyperdynamic function. In isolated subvalvular aortic stenosis, cardiac output and systolic function are well maintained until severe obstruction develops. The rate of progression of subvalvular aortic stenosis is variable and unpredictable in children, while its progression is slow in adults.

Aortic Regurgitation

The deformity in the aortic valves may develop during the course of subvalvular aortic stenosis. The membrane's fibroblastic tissue may encroach onto the aortic valve, and the high-velocity jet of blood flowing through the stenosis traumatizes the aortic valve and partly contributes to the thickening and asymmetrical post stenotic dilatation of the ascending aorta. Sixty-five percent of patients develop aortic regurgitation, which is progressive and persists even after the subvalvular aortic stenosis is surgically removed. Aortic regurgitation is usually mild; however, the severity may raise with an increasing left ventricular outflow tract pressure gradient. Due to aortic regurgitation, the left ventricle, which is already pressure-overloaded, becomes volume overloaded further increasing the left ventricular oxygen demand.

Furthermore, the decrease in aortic diastolic pressure decreases the coronary perfusion. This decrease in coronary perfusion and increase in the left ventricular oxygen demand makes the left ventricular myocardium prone to ischemic injury. Some patients may need aortic valve replacement or repair during the subvalvular aortic stenosis repair.

Histopathology

The histologic findings in subvalvular aortic stenosis are similar to the tunnel like and fibromuscular ridge lesions. Irregularly oriented dense collagen fibers and thin, short elastic fibers in ample amounts are observed. Vascularity is usually absent. Sparse fibroblasts with elongated nuclei and smooth muscle cells are observed as well.

History and Physical

Subaortic stenosis is usually detected at birth while working up the infant for another congenital heart disorder. Most infants are asymptomatic at birth or may have a murmur during evaluation. Among infants who are symptomatic, dyspnea on exertion, angina, effort syncope and presyncope, orthopnea and sudden cardiac death are commonly observed. Heart failure may be seen in infants with severe obstruction of the left ventricular outflow tract.

Exertional dyspnea is the most common symptom seen in 40% of symptomatic patients, and it reflects pulmonary venous hypertension that is induced by an increase in left ventricular filling pressure caused by the impaired diastolic compliance of the hypertrophied left ventricle.

In the presence of a severe obstruction, the cardiac output decreases resulting in systemic vasodilation causing a decline in arterial pressure and in cerebral perfusion hence causing syncope on exertion. In pediatric patients, syncope and presyncope are rare and if present, indicates a cardiac arrhythmia. The decrease in coronary perfusion coupled with an increase in oxygen demand causes angina in 25% of the symptomatic patients with a left ventricular outflow tract obstruction.

The physical examination helps to distinguish from the other causes of left ventricular outflow tract obstruction.

• Children with subvalvular aortic stenosis have a normal pattern of growth and development. Peripheral pulses are symmetrical except in cases of severe left ventricular outflow tract obstruction.
• One-third of the patients with mild subvalvular aortic stenosis is noted to have a palpable carotid thrill and a left parasternal thrill. Patients with moderate to severe subvalvular aortic stenosis have a forceful left ventricular apical impulse.
• During the first year of life, more than one-half of affected patients have a cardiac murmur. It becomes more prominent and typical of the left ventricular outflow tract obstruction as the patient gets older.[3] A low-pitched ejection systolic murmur is appreciated in the second and third left parasternal spaces, and it radiates to the suprasternal notch. The duration of the murmur is directly proportional to the degree of obstruction.
• The ejection click is absent in isolated subvalvular aortic stenosis and is an important differentiating point from the murmur of aortic valve stenosis.
• A high pitched early diastolic murmur of aortic regurgitation is heard in 30% to 50% of patients.
• The Valsalva maneuver decreases the intensity of the murmur in subvalvular aortic stenosis.

Evaluation

There are no specific laboratory blood tests that are ordered to diagnose subvalvular aortic stenosis.

Subaortic stenosis is diagnosed and confirmed using an echocardiogram.

The echocardiogram helps characterize and assess the following:

• The extent of the involvement of the left ventricular outflow tract
• The integrity of the aortic and mitral valves
• Definition and location of the subaortic valve stenosis
• The degree of left ventricular hypertrophy
• Post-stenotic aortic dilatation
• Filling characteristics
• Associated congenital heart defects
• The function of the left ventricle

However, the degree of obstruction of outflow in subvalvular aortic stenosis on a 2-dimensional echocardiogram is difficult to assess, and for this reason, Doppler imaging is indicated.[12] This noninvasive method assists in determining the precise gradient and the extent of obstruction across the left ventricular outflow tract. Using Doppler makes it possible to diagnose small subaortic membranes that cause acceleration of left ventricular outflow tract flow but without a hemodynamically significant pressure gradient.[14]

Two-dimensional echocardiography and three-dimensional echocardiography helps in evaluating the positions of the lesions, the extent of involvement of the left ventricular outflow tract and the associated defects[13]. The different views determine the relationship of the subvalvular aortic stenosis to the surrounding structures. The parasternal and the subcoastal view reveals the proximity of the subvalvular aortic stenosis to the aortic valve.

In some cases, the hypertrophied ventricular septum obstructing the left ventricular outflow tract may conceal the presence of the subaortic membrane. In such cases, transesophageal echocardiography is more reliable for the accurate diagnosis of the subaortic membrane and to distinguish subvalvular aortic stenosis from the hypertrophied ventricular septum.[9]

Other Tests

Electrocardiogram:  ECG reveals a varying degree of left ventricular hypertrophy in 50% to 80% of patients. The presence of a prominent Q wave in the left precordial leads may indicate septal hypertrophy. ECG findings may be normal in patients with severe subvalvular aortic stenosis.

Chest radiograph: The chest radiograph is often normal. Some patients, including those with mild stenosis, have mild cardiomegaly or LV prominence.

Cardiac catheterization: Cardiac catheterization is not routinely indicated in isolated subvalvular aortic stenosis. If multiple levels of obstruction are suspected, it is frequently performed to interpret the extent of subaortic obstruction further. Catheterization provides both hemodynamic and anatomic data, such as the measurement of cardiac output, the gradient across the valve, and estimates of the degree of aortic regurgitation. Associated lesions, such as aortic coarctation, can be observed. It is not indicated in the diagnosis of subvalvular aortic stenosis but can be utilized as a part of a preoperative workup to rule out significant coronary artery disease.

Treatment / Management

Since most pediatric patients are asymptomatic, medical therapy has no role in the treatment of subvalvular aortic stenosis. As it is progressive, intervention is needed at some point to relieve the left ventricular outflow tract obstruction. Surgical correction of the obstruction is the definitive therapy for the subvalvular aortic stenosis. This may range from simple removal of the membrane to extensive ring resection, with or without myectomy. However, if the patient develops heart failure or clinically significant left ventricular dysfunction, the patient is started on medical treatment until the surgery can be performed.

Indications for Intervention

The criteria and timing of intervention for subvalvular aortic stenosis are controversial. Early intervention in these patients is counterbalanced by the high postoperative incidence of recurrence, late reoperation and development of aortic regurgitation after relieving the obstruction.[14],[15]

• In children and adolescents with Doppler mean gradient of less than 30 mm Hg and no left ventricular hypertrophy, the management of subvalvular aortic stenosis is nonintervention and medical follow up.[17]
• In children and adolescents with Doppler mean gradient of 50 mm of Hg or more should be surgically treated
• In children and adolescents with Doppler mean gradients of 30 to 50 mm Hg, may be considered for surgery if they are symptomatic with angina, syncope, or dyspnea on exertion if they are asymptomatic but develop changes on ECG at rest or with exercise or older age at diagnosis.[17],[18],[4]
• Prevention of aortic regurgitation alone is generally not a criterion for surgery. However, the progression and worsening of regurgitation to a significant grade is an indication for surgery.

Interventional Procedures

Surgery requires the use of the heart-lung machine. The subaortic membrane is usually resected via the aorta (myomectomy). Some children with subvalvular aortic stenosis may require an aortic valve repair or replacement at the same time. In infants who are too ill to undergo open-heart surgery, percutaneous balloon dilatation can be performed. If successful it will reduce the aortic gradient and symptoms. This palliative procedure will last for a few months or even years, and the child can undergo formal surgery when stable.

Discrete fibromuscular subvalvular aortic stenosis is treated surgically by complete resection with myotomy, with or without myomectomy through an aortotomy. Clinically significant aortic regurgitation may require aortic valve repair or replacement.

In tunnel-type subvalvular aortic stenosis with a small LV-aortic junction, Konno procedure (aortoventriculoplasty) may be needed. This includes excision and replacement of the aortic valve with a prosthesis, and patch augmentation of ventricular septum to enlarge the left ventricular outflow tract, and then pericardial patch closure of the right ventriculotomy used to gain access to the left ventricular outflow tract.

In cases of recurrent subvalvular aortic stenosis and tunnel-type subvalvular aortic stenosis with the normal LV-aortic junction and aortic valve, modified Konno procedure, in other words, without aortic valve excision and replacement may be performed.

Endocarditis Prophylaxis

In the 2007 American Heart Association guidelines, antibiotic prophylaxis to prevent bacterial endocarditis is no longer recommended in patients with subvalvular aortic stenosis, except in those with a prior history of endocarditis or with a repair that required prosthetic material or device. 

In the latter case, antibiotic prophylaxis is recommended for the first 6 months after repair. However, if a residual defect is present, prophylactic antibiotics are continued beyond the 6-month period.

Differential Diagnosis

Subvalvular aortic stenosis commonly presents with a ventricular septal defect, coarctation of the aorta, patent ductus arteriosus, bicuspid aortic valve, and atrioventricular septal defect. 

The following congenital heart conditions mask symptoms of subvalvular aortic stenosis:

1. Hypertrophic cardiomyopathy
2. Bicuspid aortic valve
3. Supravalvular aortic stenosis
4. Valvular aortic stenosis

Prognosis

Infants and children should be followed up frequently (every 4 to 6 months) to understand the rate of progression as subvalvular aortic stenosis is a progressive disorder.

The survival in patients who undergo surgery to excise the subaortic membrane is excellent, but these individuals need to be followed up as the left ventricular outflow tract gradient increases slowly over time. Long-term follow-up care in postoperative patients is important. Most patients will need reoperation for recurrence at some point in their lifetime.[12]

The independent predictors for increased reoperation rate are as follows[12]:

1. Female gender
2. Peak instantaneous LVOT gradient progression over time
3. Difference between preoperative and postoperative peak instantaneous LVOT gradients
4. Preoperative peak instantaneous LVOT gradient greater than or equal to 80 mm Hg
5. Age older than 30 years at diagnosis

Complications

Postoperative complications of bundle branch or complete heart block, iatrogenic ventricular septal defect, mitral valve injury, aortic regurgitation as well as incomplete relief and/or recurrence of obstruction and infective endocarditis (IE) have been reported.

Postoperative and Rehabilitation Care

Activity restrictions depend on the degree of residual hemodynamic abnormality. Avoid participation in strenuous activities and competitive sports.

Competitive sports and games and strenuous exercises should not be permitted in the following situations:

1. Clinically significant left ventricular outflow tract obstruction (peak echo pressure gradient greater than 50 mm Hg)
2. Marked left ventricular hypertrophy
3. Clinically significant ventricular or supraventricular arrhythmia
4. More than mild aortic regurgitation

Consultations

Consultation with a pediatric cardiologist and a cardiac surgeon as needed is advisable.

Enhancing Healthcare Team Outcomes

The diagnosis and management of subaortic stenosis is best accomplished with an interprofessional team that consists of a pediatrician, cardiologist, radiologist, cardiac surgeon, neonatologist, and specialty trained nurses. Management requires assistance of a specialty trained nurse to assist with patient monitoring, coordination of care, and family education. The follow up of these infants is usually by the primary care provider and nurse practitioner. Surgical resection of the membrane is the only treatment for subaortic stenosis. The surgery is palliative as in most cases, the membrane will recur later in life, making another open-heart procedure necessary. Most infants have a good outcome after surgery, provided that they do not have other congenital problems. Life long follow-up is necessary as many will require REDO surgery to resect the membrane again later in life. [16] (Level V)