Patients with left ventricular outflow tract (LVOT) obstruction comprise a diverse group of neonates, infants, children, and young adults, accounting for up to 6% of adults with congenital heart disease (CHD). Congenital LVOT obstruction can occur at three levels; in approximately 50% of cases the obstruction is valvar, in around 30% it is subvalvar, and in the remainder it is supravalvar or multilevel. A small proportion of patients with subvalvar aortic stenosis (SAS) may present for the first time as adults, but more commonly there has been recurrence of previously resected subvalvar obstruction. Likewise, significant supravalvar aortic stenosis (SVAS) rarely presents as an isolated lesion in adults and is more often due to residual obstruction following a surgical repair in childhood or as part of the spectrum of pathologic processes in patients with Williams syndrome.
The physical findings of SAS and SVAS are similar, but the epidemiology, natural history, and treatment are quite different. They are therefore discussed as separate clinical entities.
Subvalvular Aortic Stenosis
Definition and Morphology
SAS comprises 8% to 30% of all forms of congenital LVOT obstruction. It spans a spectrum of anomalies ranging from a simple fibrous membrane to a tunnel-like fibromuscular band. The lesion itself is produced by an accumulation of fibroelastic tissue. The most common clinical presentation, in approximately 84% of cases, is as a fibrous crescent or ring that completely encircles the LVOT to produce a discrete obstructive lesion. In its more severe form, a fibromuscular band encircles the complete length of the LVOT, producing a diffuse, tunnel-like narrowing. This tunnel-like obstruction commonly occurs in association with a small aortic root. The resultant outflow obstruction causes myocardial hypertrophy, which may in turn add to the severity of the obstruction.
Subaortic stenosis may also result as a consequence of abnormal mitral valve insertion, accessory mitral apparatus tissue, abnormal insertion of papillary muscles, abnormal muscular bands in the LVOT, or posterior displacement of the infundibular septum. Subaortic stenosis can develop after surgical repair of atrioventricular septal defects, ventricular septal defects, double-outlet right ventricle, or after the arterial switch operation.
Associated Lesions
SAS can be isolated or found in association with other heart defects (∼60% of cases), particularly multilevel LVOT obstruction. Other associated congenital cardiac anomalies include ventricular septal defect, coarctation of the aorta, Shone syndrome (aortic coarctation, parachute mitral valve, supramitral valve ring, subaortic stenosis), patent ductus arteriosus, left superior vena cava, and valvular aortic stenosis. There may be an association between SAS and familial hypertrophic cardiomyopathy.
Genetics and Etiology
There is clinical and experimental evidence that isolated discrete SAS is an acquired lesion. There have also been reports of familial occurrence implying a genetic predisposition. There are, however, no antenatal reports of this lesion and it has never been described in neonates. Furthermore, no SAS has been described in experimental genetic mouse models. The pathological initiator of SAS is likely to reside in the myocardium, but the mechanism by which the abnormal hypertrophic response within the LVOT is generated is as yet unclear. Subtle morphologic abnormalities of the LVOT (a steeper aortoseptal angle) may result in altered shear stress on the outflow septum, triggering cell proliferation in this region in the genetically predisposed individual.
Early Presentation and Management
SAS is usually a progressive lesion. The rate of progression is variable, but it tends to be more rapid in those with tunnel-type obstruction. Progression of subaortic stenosis in children may be quite rapid, particularly in patients with a higher LVOT gradient at baseline and those diagnosed at a younger age. In contrast, the rate of progression of obstruction in patients diagnosed in adulthood tends to be slower, with an annual increase in LVOT gradient of less than 1 mm Hg and a median intervention-free survival of 16 years. The presence of associated congenital lesions may identify those at risk of more rapid progression, but neither age at diagnosis or baseline LVOT gradient appear to be predictive in adults. Campbell reported a 1.4% annual mortality and 0.9% sudden death rate per year in a review of 2816 nonsurgically treated cases of valvar or subvalvar aortic obstruction from six separate series.
The predominant pathophysiologic features of SAS are progressive left ventricular hypertrophy and a variable degree of aortic valve regurgitation. It is believed that the “jet lesion” through the obstructed outflow tract causes shear stress on the aortic valve cusps, initiating a secondary fibrous thickening of the valve endothelium. More rarely, there can be fibrous attachments from the subaortic membrane to the valve cusps, which impair valve function. Mild to moderate aortic regurgitation is therefore common (60% of cases).
Outpatient Assessment
Clinical presentation depends on the severity of outflow tract obstruction and whether there are associated lesions. Those patients presenting for the first time in adulthood are often referred for evaluation of a heart murmur. Symptoms are rare if the obstruction is mild, but exertional breathlessness, chest pain, or syncope may occur if there is moderate or severe obstruction.
On physical examination, the pulse volume may be reduced if the outflow obstruction is severe or increased if there is moderate to severe aortic regurgitation. There may be a left ventricular heave if there is left ventricular hypertrophy (LVH) and/or a palpable systolic thrill over the mid-left (tunnel stenosis) or upper right sternal edge (discrete stenosis). The first heart sound is normal. The second heart sound may be normal or diminished (reduced intensity of A 2 ) depending on the severity of the stenosis. A crescendo-decrescendo systolic ejection murmur is audible either at the left mid-sternal border (tunnel) or right-upper sternal border (discrete). Transmission into the carotids is inconsistent. Unlike valvular aortic stenosis, no ejection click is heard. A blowing, decrescendo diastolic murmur is heard if there is aortic regurgitation.
On the electrocardiogram, LVH is seen in 65% to 85% of all patients and in up to 50% of those with even mild stenosis. Left atrial enlargement may be present. In postoperative patients, there may be left bundle-branch block.
The chest radiograph is often normal, or there may be prominence of the left ventricle with associated dilation of the ascending aorta. Left ventricular dilation may be seen if there is significant aortic regurgitation.
Transthoracic echocardiography will demonstrate a narrow LVOT, seen best in the parasternal long-axis (PLAX) view. A “membrane” or ridge is sometimes visualized (owing to limited acoustic window), or a long area of muscular thickening (tunnel type) may be seen. Fluttering or partial early closure of the aortic valve may be seen on two-dimensional (2D) or M-mode echocardiography.
Transesophageal echocardiography usually allows direct imaging of the subaortic “membrane” or ridge, especially if multiplanar imaging is used. The transverse and longitudinal views of the aortic valve and LVOT provide comprehensive definition of discrete membranes ( Fig. 36.1 ) and evaluation of aortic valve competence. The five-chamber transgastric view allows color flow demonstration of the level of obstruction and estimation of pressure gradients by spectral Doppler imaging. Advanced real-time three-dimensional transesophageal echocardiographic techniques have been increasingly used for spatial assessment of subaortic membranes and in quantification of the extent of subaortic stenosis for preoperative planning.
Continuous wave and color flow Doppler imaging quantifies the severity of subaortic obstruction. The severity of discrete stenosis can be estimated using the simplified Bernoulli equation (peak gradient = 4 V 2 ), which calculates a peak instantaneous Doppler gradient. This gradient can be higher than the numerical figure of the peak-to-peak gradient recorded at cardiac catheterization and may vary with different loading conditions, heart rate, cardiac output, and circulating catecholamines, with beat-to-beat and respiratory variation.
The Doppler mean gradient is also useful, taking an average of all instantaneous gradients throughout systole (calculated by tracing the outside border around the continuous wave Doppler velocity profile, using commercially available computer software). Doppler gradient estimation is less accurate with the tunnel form of obstruction, because it neglects the pressure drop caused by viscous friction along its flow path and invalidates some of the physical assumptions in the Doppler gradient calculation. Three-dimensional (3D) echocardiography may also provide more accurate definition of these lesions.
Magnetic resonance imaging (MRI) provides an accurate noninvasive assessment of this lesion in both its forms. Spin-echo images define morphology, and gradient reversal images can be utilized to estimate the severity of obstruction. Associated anomalies can also be detected.
Right-sided and left-sided heart catheterization can assess the severity of outflow obstruction by recording pressure withdrawal gradients (peak-to-peak pressure gradients) across the respective outflow tracts. Left or right ventriculography can assess ventricular function and delineate the level of obstruction of both discrete and diffuse forms. End-hole or micromanometer-tipped catheters can be used to obtain accurate measurements. Aortography will confirm the presence and severity of aortic regurgitation and associated arch abnormalities.
A combination of investigations may be needed to confirm the diagnosis, define the anatomy, assess the severity of the lesion, and detect associated anomalies.
Management
SAS tends to be a progressive lesion with a variable rate of progression. The management of asymptomatic patients is not well defined. The timing of intervention and choice of surgical technique remains controversial. Some advocate early surgery even in the absence of symptoms, to prevent aortic valve damage and recurrence, whereas others adopt a more conservative “watch and wait” approach before performing myectomy and membrane excision.
In the asymptomatic young adult, a resting peak instantaneous Doppler gradient of more than 50 mm Hg, a mean Doppler gradient of more than 30 mm Hg, the presence of moderate-to-severe aortic regurgitation, and left ventricular dilation, are used as criteria for intervention. In patients with lower peak gradients, symptoms can be investigated with exercise testing or exercise Doppler imaging to document the gradient increase with exertion.
The controversy regarding timing of surgical intervention reflects conflicting outcome data from mid- and long-term surgical follow-up. A persistent problem is a high postoperative recurrence of SAS (occurring in up to 27% of cases) and the need for late reoperation. The development of progressive aortic regurgitation is also seen (12% to 20% cases) even after successful relief of obstruction. Although recurrence of stenosis is reportedly lower (15%) in those who have early surgical repair, reoperation will be required in some.
For symptomatic patients, who may or may not have had prior surgery, relief of outflow obstruction is needed. Balloon dilation of discrete thin membranes has been described as a safe and effective method of reducing subaortic obstruction, but surgery is traditionally regarded as the preferred treatment option. Surgery is particularly preferred in adults when definitive repair can be performed. The choice of surgical technique remains an area of discussion.
Percutaneous balloon dilation for discrete SAS was first described in 1985. Adolescents or young patients with a thin membrane causing a significant gradient (>50 mm Hg), with or without symptoms, may be candidates for this intervention. The membrane should be no more than 1 to 2 mm thick, and transesophageal echocardiography and fluoroscopy should be used to define the anatomy and guide intervention. A balloon diameter 1 to 2 mm bigger than the aortic valve annulus diameter is used, with a balloon length of 40 to 60 mm. A visible notch in the balloon can be seen during fluoroscopy that should then disappear as the membrane is torn. Early relief of obstruction has been described, but there are few long-term follow-up studies, and a recurrence rate of up to 15% is reported. The technique seems ineffective for membranes with a fibromuscular collar or tunnel-type lesions.
The surgical technique used to relieve SAS depends on the nature of the obstructive lesion. For a discrete obstruction, a membranectomy with or without myomectomy is performed. Myomectomy is favored by several authors who demonstrated better initial and long-term results, with a reduction in recurrence rates of SAS. Others, however, have found no difference in recurrence rates between membranectomy alone or membranectomy plus myectomy. Whichever technique is used, it appears that the main determinant of long-term outcome is the quality of the initial relief of obstruction. The operative mortality is low (0% to 6%).
For tunnel obstruction, the operative mortality is higher in all series. Several types of repair can be performed depending on the size and function of the aortic valve. The valve-sparing (modified Konno) procedure involves patch augmentation of the LVOT to the aortic annulus without aortic valve replacement (aortoventriculoplasty with sparing of the aortic valve). If there is significant aortic regurgitation, then aortic valve replacement is necessary in addition to aortoventriculoplasty (Konno procedure).
The Ross-Konno procedure has also been used in infants with tunnel obstruction and a diminutive aortic annulus. This procedure incorporates the principle of aortic root replacement with a pulmonary autograft and outlet septum enlargement. This procedure provides a new alternative for definitive treatment of this anomaly. Short- and mid-term follow-up data are encouraging with a low operative mortality (1.5%) and good durability.
Surgical complications include complete atrioventricular block necessitating permanent pacemaker implantation, perforation of the interventricular septum (acquired ventricular septal defect), and damage to the mitral valve apparatus causing mitral regurgitation.
Late Outcomes and Complications
Recurrence or persistence of outflow tract obstruction is common in most published series with recurrence rates between 14% and 27%. An average time to recurrence of 3.6 to 4.7 years has been reported. The quality of initial relief of obstruction is the main determinant of recurrence. A peak postoperative systolic LVOT gradient greater than 30 mm Hg, by direct pressure measurement or by Doppler assessment (using the Beekman formula: Peak systolic gradient = 6.02 + 1.49 [mean systolic gradient] − 0.44 [pulse pressure]), has been shown to be an independent risk factor for recurrence of SAS. A resection that reduces immediate postoperative peak LVOT gradient to less than 30 mm Hg is therefore recommended. The preoperative LVOT gradient is also recognized as a risk factor for recurrence with a preoperative catheter or mean Doppler gradient greater than 40 mm Hg associated with a higher rate of recurrence. For patients with discrete SAS, proximity of the lesion to the aortic valve may predict recurrence. Recurrence rates are also higher and more rapidly progressive in those with diffuse tunnel-type obstruction.
Moderate-to-severe late aortic regurgitation is reported in 25% to 40% of cases during long-term follow up. The strongest single predictor of late aortic regurgitation is a significant degree of preoperative aortic regurgitation, even when relief of obstruction has been adequate. A preoperative peak LVOT gradient greater than 40 mm Hg also predicts late progression of aortic regurgitation. Similarly, in children who have not had percutaneous intervention or surgical repair, higher gradients are associated with late moderate-to-severe aortic regurgitation. Thin mobile aortic valve leaflets and an associated ventricular septal defect seem to be protective. Reoperation rates vary between 12% and 20%. Indications for reoperation include relief of recurrent subaortic obstruction, severe aortic regurgitation, and aortic valve endocarditis ( Box 36.1 ).
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Subvalvar aortic stenosis is usually progressive.
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Balloon angioplasty may be useful in symptomatic patients with a thin discrete membrane (no long-term data are available).
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Surgery is recommended for symptomatic patients or if there is a peak Doppler instantaneous left ventricular outflow tract gradient greater than 50 mm Hg or mean gradient greater than 30 mm Hg with or without severe aortic regurgitation and left ventricular dilation.
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Recurrence of subvalvar aortic stenosis and moderate-to-severe aortic regurgitation are common postoperative occurrences.
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Long-term follow-up and surveillance of all patients is needed.
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Endocarditis prophylaxis is recommended only in those with prosthetic material used in the surgical repair.
Valvular aortic stenosis requiring surgical intervention is also common and surgical intervention may be required more frequently for this condition than for regurgitation. Associated bicuspid aortic valves and coarctation are associated with a higher prevalence of valvar aortic stenosis in this cohort.
Level of Follow-up
Long-term surveillance is needed for all patients with SAS whether asymptomatic operated, asymptomatic unoperated, or reoperated. For asymptomatic unoperated patients, regular clinical review and transthoracic echocardiography are needed to assess symptom status, LVOT gradient, left ventricular wall and cavity dimensions, and monitoring of aortic regurgitation. Patients who have undergone prior surgical resection of SAS require surveillance for recurrence of obstructive SAS and development of progressive or late aortic regurgitation. At least yearly follow-up is recommended for these groups. Young women should be counseled that the hemodynamic effects of pregnancy will increase any preexisting gradient, possibly making them symptomatic.
Guidelines regarding endocarditis prophylaxis have recently changed in the United Kingdom. Differences in various guidelines are detailed in Table 36.1 .
| European Society of Cardiology, 2015 | Antibiotic prophylaxis recommended for
Not recommended in other forms of valvular or congenital heart disease. (Class III, Level of Evidence C) |
| American Heart Association/American College of Cardiology, 2008 | Antibiotic prophylaxis is recommended for
|
| National Institute of Health and Clinical Excellence Guidelines (UK), 2008 |
|
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