Morphology and classification

Subaortic stenosis may occur in isolation or in association with other congenital heart defects such as ventricular septal defect, atrioventricular canal defect, bicuspid (bicommissural) aortic valve, aortic valve stenosis, coarctation of the aorta, interruption of the aortic arch, and double‐chambered right ventricle [18–20]. In addition, subvalvar aortic stenosis may accompany conotruncal anomalies and complex anomalies, including transposition of the great arteries, double‐outlet right ventricle, and single ventricle. Abnormalities of the insertion of the mitral valve or accessory mitral valve tissue may also coexist [21]. Variation in the morphology of the left ventricular outflow tract obstruction can have several causes:

1. Hypertrophic cardiomyopathy: hypertrophy of the ventricular septum can result in muscular obstruction of the left ventricular outflow tract. This may be accompanied by abnormal systolic anterior motion of the mitral valve. This is dealt with in more detail in Chapter 35.
   
2. Discrete “membranous” subaortic stenosis (Figures 20.1 and 20.2, Video 20.1): this form of subaortic stenosis usually manifests during childhood and is rare during infancy [22]. In some cases, there may be multilevel obstruction due to chordal attachments in the left ventricular outflow tract (Figures 20.3 and 20.4, Video 20.2). It is important to assess the morphology of the aortic valve and assess for aortic valve regurgitation (Videos 20.3 and 20.4). The morphology of the left ventricular outflow is characterized by a steeper angle between the plane of the ventricular septum and the aortic root (aortoseptal angle), elongation of the intervalvular fibrosa between the anterior mitral leaflet and the aortic valve, and an exaggerated aortic override above the ventricular septal crest [23]. There is a frequent association with a membranous ventricular septal defect, and abnormal shear stresses have been implicated by causing abnormal proliferation of fibrous tissue. Although such discrete obstruction is amenable to surgical repair, regrowth of tissue may lead to recurrence of subaortic obstruction [24–27]. Note that the obstructive subaortic tissue may not be limited to the ventricular septum and may extend onto the anterior leaflet of the mitral valve (Figure 20.2, Video 20.1) as well as the ventricular aspect of the aortic valve leaflets. Use of 3D echocardiography can assist in visualizing the anatomy of subaortic stenosis, with visualization possible from both the aortic side and ventricular side of the suboartic obstruction (Videos 20.4 and 20.5).

   

   

   
   
3. “Tunnel‐type” subaortic stenosis (Figure 20.5, Video 20.6): as the name implies, this form of subaortic stenosis involves a long segment of narrowing of the left ventricular outflow tract and is often caused by muscle. The muscular narrowing can involve an accessory anterolateral papillary muscle, septal hypertrophy, or a combination of the above. This form of obstruction frequently occurs early in life and is often associated with other forms of left heart obstruction. The clinical implication is that a more extensive type of surgical repair will be required compared with repair of the discrete fibrous form of obstruction [28,29].
   
4. Posterior deviation of the infundibular (outlet, conal) septum may cause subaortic obstruction [30]. This typically occurs in association with conditions such as type B interruption of the aortic arch or, less commonly, coarctation of the aorta with ventricular septal defect, where the aortic valve and ascending aorta may be hypoplastic.

Pathophysiology

The development of subaortic stenosis is thought to be due to abnormal shear forces in the left ventricular outflow tract, leading to abnormal growth of fibrous tissue [15,17,31]. Such shear forces are increased in the presence of an abnormal aortoseptal angle and other lesions such as a ventricular septal defect. The obstruction to the left ventricular outflow tract leads to compensatory ventricular hypertrophy. Contractile function of the left ventricle is usually well maintained initially but may worsen with time if severe outflow tract obstruction is not relieved. The fibrous tissue below the aortic valve may extend onto the aortic valve leaflets and contribute to obstruction of the left ventricular outflow tract. The turbulent jet across the subaortic region may also interfere with optimal motion of the aortic valve and may contribute to dysfunction of the aortic valve, including aortic valve regurgitation. Consequently, some centers have advocated early surgical resection of the subaortic lesion to reduce the risk of aortic regurgitation [25,26], a strategy that has not been consistently adopted [31,32]. There is a clear indication for surgical intervention where there is severe left ventricular outflow tract obstruction. The indications for intervention in children with relatively mild outflow tract obstruction are less clear‐cut. As a minimum, serial echocardiographic examination is required because rapid progression of subaortic stenosis may occur in infancy and early childhood [26]. For adults with relatively low Doppler‐derived gradients (<50 mmHg), a conservative approach may be adopted although progression may occur during adult life, albeit more slowly than in infancy and early childhood [26,33].

Imaging

The goals of echocardiographic assessment of subvalvar aortic stenosis are to comprehensively characterize the morphologic features of the obstructive lesion, to evaluate the hemodynamic severity, and to delineate associated anomalies.

The assessment of severity of left ventricular outflow tract obstruction can be done in a manner analogous to that of aortic valve stenosis (see “Aortic valve stenosis” later in this chapter). Muscular subaortic obstruction may be accompanied by an increase in the Doppler velocity in late systole leading to an asymmetric Doppler trace consistent with dynamic obstruction. To obtain optimal Doppler signals, imaging is undertaken from the apical and from the suprasternal notch views. PW Doppler is helpful to localize flow acceleration and, in patients with several levels of obstruction, to determine the contribution of each location to the total estimated pressure drop. The maximum instantaneous and mean gradients across the left ventricular outflow are also recorded from both transducer positions by CW Doppler, with particular attention to optimization of the alignment between the ultrasound beam and the direction of flow. A detailed discussion of the principles of assessing stenosis by Doppler can be found in Chapter 6.

Imaging of the morphology of the left ventricular outflow tract is crucial for planning management. In the membranous form of subaortic stenosis the full extent of the fibrous membrane should be defined, as such membranes vary in their distance from the aortic valve itself, and some extend circumferentially to involve the anterior leaflet of the mitral valve. This assessment is best achieved from the parasternal long‐ and short‐axis views. 3D imaging allows en face views of the subaortic obstruction from the left ventricular cavity and through the aortic valve (Figure 20.6). In some patients, accessory tissue related to the mitral valve attaches to the subaortic septum, producing or contributing to subaortic stenosis [34]. The aortic valve may be intrinsically abnormal or be restricted in its motion due to encroachment of fibrous tissue onto the ventricular aspect of the leaflets. The aortic valve leaflets may “flutter” during systole as they are hit by the turbulent jet from the subaortic region (Figure 20.7).

Comprehensive echocardiographic evaluation is crucial for planning subaortic stenosis surgery. Discrete “membranous” subaortic stenosis may be resected with preservation of the native aortic valve. However, “tunnel” forms of subaortic stenosis may not be able to be managed by resection of a localized area of tissue and may require a more extensive resection [24,28,29,35]. It is therefore essential to have all anatomic information before surgical repair. In the tunnel type of subaortic obstruction, the left ventricular outflow tract, including the aortic valve annulus, is often hypoplastic. In selected patients, extensive subaortic resection may have to be combined with insertion of the patient’s pulmonary valve into the aortic position (Ross–Konno operation) [36,37]. In small infants, transthoracic echocardiographic imaging is usually all that is necessary to plan treatment, but in older children and adults, transesophageal echocardiography (TEE) may be necessary to gain all relevant information. In some patients, subaortic obstruction follows the repair of more complex forms of congenital heart disease [38]. An example of this would be subaortic obstruction following a “Rastelli” type of repair for conditions such as transposition of the great arteries with a ventricular septal defect and pulmonary stenosis. In this repair, the outflow from the left ventricle is baffled to the aorta via the ventricular septal defect, using a patch. The tortuous outflow tract is a substrate for subaortic obstruction (Figure 20.8). Subaortic stenosis may also develop following complete repair of an atrioventricular canal defect which may be related to the unwedged position of the native aorta and elongation of the left ventricular outflow tract (Figure 20.9). Other examples include conditions such as double‐inlet left ventricle with transposition of the great arteries, where the outlet of the left ventricle to the ascending aorta is through a ventricular septal defect, which, if restrictive, effectively causes subaortic obstruction.

Intraoperative and postoperative assessment

Intraoperative imaging, either by an epicardial or TEE approach, is typically performed in cases of subaortic stenosis, whatever the anatomic substrate, to confirm adequacy of the surgical relief of obstruction. Alignment of the Doppler cursor to the direction of flow is typically best achieved by a transgastric approach but this can be difficult or impossible when the chest is open during surgery. The severity of aortic regurgitation should be assessed because this can occasionally worsen following removal of the fibrous subaortic obstruction, particularly in cases where fibrous tissue has extended onto the aortic valve leaflets themselves. The mitral valve should be imaged for evidence of mitral valve regurgitation (four‐chamber, 90°, and 120° views) as damage to the anterior leaflet may occur if a circumferential subaortic “membrane” has had to be surgically resected from the anterior mitral valve leaflet. Finally, it is necessary to guard against iatrogenic creation of a ventricular septal defect due to inadvertent perforation of the ventricular septum so this region should be scanned comprehensively.

In the longer term, sequential echocardiography is indicated to exclude the recurrence of subaortic stenosis, which can occur even after initial apparent complete resection of the obstructive tissue. The risk of recurrence is higher when the subaortic “membrane” is closer to the aortic valve and in patients with severe preoperative obstruction [27,39]. Those with previously operated aortic arch interruption are also at particularly high risk for recurrence [40]. Aortic regurgitation should be assessed semiquantitatively and chamber dimensions, wall thickness, and contractile function should be measured.

Morphology and classification

Aortic valve stenosis in children is due to a congenitally abnormal aortic valve rather than degeneration of a normal valve as may occur in late adult life. Morphologically, the anomaly may be due to commissural underdevelopment, myxomatous thickening of the valve leaflets, annular hypoplasia, or a combination of these elements. As a result of commissural underdevelopment, the aortic valve may be unicuspid (when only one commissure, usually the left noncoronary commissure, is well formed), bicuspid (when one commissure is underdeveloped and the other two are well formed), tricuspid (all three commissures are well developed), or, rarely, quadricuspid (when an extra commissure is present). 3D echocardiography has the potential to assist in defining valve morphology by permitting display of a depth of field so that both cusps can be visualized (Figure 20.10, Video 20.7). The morphology of the bicuspid aortic valve has assumed greater importance with recent surgical advances in repair rather than replacement of such valves [41]. In some cases, particularly in infancy, it may be difficult to identify true separate cusps, with the appearance of a single central or eccentric orifice, which has been likened to a “volcano‐type” or “keyhole” orifice [42]. In some patients the valve may be incompetent and stenotic. Aortic regurgitation is almost invariably present following balloon valvuloplasty, either surgical or transcatheter. Post‐stenotic dilation of the proximal ascending aorta also occurs due to the high velocity, turbulent, and often eccentric jet through the valve.

Pathophysiology

Obstruction to the left ventricular outflow tract results in an increased afterload on the left ventricle. The myocardial response to the excess load depends on the stage of development at which it occurs. During fetal life, mild stenosis of the aortic valve is usually well tolerated with good contraction of the left ventricle and normal development of left heart structures. In fetuses with severe aortic valve stenosis, the left ventricle dilates, contractile function decreases, and endocardial fibroelastosis often develops [43]. As gestational age advances, growth of the left ventricle and aorta is inhibited in the majority of cases so that, by term, the left ventricle and aorta are hypoplastic and postnatal management is more akin to that of hypoplastic left heart syndrome [43,44]. Such progression of aortic stenosis provides the rationale for intrauterine intervention to prevent progression of aortic valve stenosis to hypoplastic left heart syndrome, with the potential to improve the likelihood of a biventricular repair postnatally [45–47].

Following birth, once the ductus arteriosus closes, the systemic arterial circulation has to be supported entirely by left heart structures. If there is severe aortic stenosis with significant left ventricular dysfunction and/or underdevelopment of left heart structures, then the left heart may be unable to support the circulation and the infant will present with cardiovascular collapse. In such circumstances, the administration of prostaglandin is life‐saving to allow reopening of the the ductus arteriosus and permit the right heart structures to support the systemic circulation. The term “critical” aortic stenosis is commonly applied to infants where the systemic circulation is dependent on the maintenance of ductal patency. In less severe cases, closure of the ductus arteriosus does not lead to left ventricular failure because the left ventricle hypertrophies in response to left ventricular outflow tract obstruction and maintains an adequate cardiac output. Such infants and children may remain asymptomatic early in life and present for other reasons such as cardiac murmur, reduced exercise tolerance, or exercise‐induced syncope. In adults, aortic valve stenosis may develop due to degeneration of an aortic valve that was not previously stenotic. Individuals with a congenitally bicuspid aortic valve have a higher risk of late degeneration of the valve than if the valve is tricuspid [48].

Imaging

The goals of echocardiographic assessment of aortic valve stenosis are to comprehensively characterize the morphologic features of the obstructive lesion, to evaluate the hemodynamic severity, and to delineate associated anomalies.

The severity of aortic valve stenosis is estimated by measurement of the Doppler‐derived maximum instantaneous and mean pressure drop across the aortic valve. Classification by Doppler‐derived pressure drop is only valid if left ventricular function is well preserved and cardiac output is normal. Assuming this to be the case, and beyond the neonatal age range, mild aortic valve stenosis may be defined as a peak Doppler velocity of less than 3 m/s; moderate aortic valve stenosis has a peak velocity of 3–4 m/s; and severe aortic stenosis is characterized by a peak velocity of more than 4 m/s. Color Doppler flow mapping is extremely helpful in observing the direction of the flow jet, which may be eccentric, and allows optimal alignment of the Doppler cursor with the jet (Figure 20.11). Imaging from the suprasternal notch often has the best alignment with the direction of flow. Use of the low‐frequency CW pedoff Doppler probe is recommended as it provides optimal access to the suprasternal notch, particularly in smaller children. In infants and children an apical three‐chamber projection provides an excellent window for Doppler interrogation of the left ventricular outflow tract. CW Doppler is optimal to determine the maximum instantaneous and mean Doppler‐derived pressure drop, but PW Doppler is extremely helpful in patients with multiple levels of left ventricular outflow tract obstruction. This is because “step up” in velocity at different sites may be observed and allows determination of the relative contribution of the different levels of obstruction.

In older children and in young adults with congenital aortic valve stenosis, an assessment of valve area can be made by employing the continuity equation [49,50] or other formulae [51,52]. In adults with mild aortic valve stenosis, the effective orifice area is >1.4 cm²; in moderate aortic valve stenosis it is 1.0–1.4 cm²; and in severe aortic valve stenosis it is <1.0 cm² [53]. One important group has relatively low “gradients” across the aortic valve due to reduced left ventricular ejection fraction resulting in a reduced cardiac output. In this group, severe aortic valve stenosis coexists with a relatively low Doppler velocity across the aortic valve. Dobutamine stress echocardiography examines for increases in effective orifice area, contractile function, and pressure gradient under stress conditions, permitting stratification of risk for surgery [53].

The morphology of the aortic valve in the assessment for bicuspid or unicuspid valve, is best seen with a parasternal short‐axis view of the aortic valve. The diameter of the aortic valve annulus is measured during systole from the parasternal long‐axis view. If there is aortic regurgitation, the parasternal short‐axis view is ideal for determining the site of regurgitation through the valve. 3D echocardiography can provide further information because the depth of field permits visualization of the whole cusp rather than the single cut plane of cross‐sectional techniques (Figure 20.12). Assessment of aortic regurgitation is discussed in detail in Chapter 6. Briefly, the severity can be assessed by the width of the vena contracta of the aortic regurgitation jet using color flow mapping from the parasternal long‐axis view, relative to the aortic annulus diameter. CW Doppler interrogation of the regurgitant jet can be used to estimate the pressure half‐time, and the degree and duration of reversal of flow in the distal aortic arch or descending aorta during diastole can be helpful to give a semiquantitative assessment of the degree of aortic valve regurgitation [54]. Holodiastolic reversal in the abdominal aorta is generally considered severe aortic regurgitation.

In all cases of left ventricular outflow tract obstruction at any level, left ventricular dimensions and wall thickness should be carefully measured. These measurements can be obtained by cross‐sectional or M‐mode echocardiography of the left ventricle at the level of the tips of the mitral valve in either a parasternal long‐ or short‐axis projection. Alternatively, left ventricular volume, mass, and systolic function can be measured by 2D or 3D techniques (see Chapter 7 for further details). It is essential that Doppler‐derived pressure drop across a stenotic aortic valve is interpreted in light of left ventricular contractile function and blood flow rate. An example of this occurs in small infants with severe aortic stenosis in whom left ventricular contractile function may be so poor that only low‐velocity jets are observed across a critically stenotic aortic valve.

A thorough examination of all left heart structures is essential when aortic valve stenosis is diagnosed. Aortic valve stenosis may coexist with other types of left heart obstruction including supramitral membrane, congenital mitral valve stenosis, subaortic stenosis, and coarctation of the aorta. In infancy, critical aortic stenosis is frequently accompanied by hypoplasia of left heart structures including the mitral valve, left ventricle, and aorta (Figures 20.13–20.15). Endocardial fibroelastosis is observed as a brightly echogenic lining to the left ventricle; in its mildest form this may involve only patchy areas of the papillary muscles but in its severest form it may line the entire left ventricular cavity (Figures 20.14 and 20.15). Estimation of the extent and severity of endocardial fibroelastosis may be assisted by magnetic resonance imaging (MRI) (Figure 20.16). In severely affected infants it may be difficult to judge whether left heart structures are capable of supporting the systemic arterial circulation or not. This poses a major challenge in terms of management because if left heart structures are judged adequate, an intervention to relieve the aortic valve stenosis may be attempted. However, if left heart structures are judged inadequate to support cardiac output a single ventricle (“Norwood”) palliation is generally adopted. Echocardiographic criteria have been developed to aid in decision‐making in this regard [55–57] and an online calculator developed by the Congenital Heart Surgeons’ Society is available (http://www.chssdc.org/content/chss‐score‐neonatal‐critical‐aortic‐stenosis; last accessed January 2021).

Aortic valve stenosis in the fetus

Aortic valve stenosis may be diagnosed accurately during fetal life [43–45]. In mild cases of aortic stenosis, there is an increased Doppler velocity across the aortic valve with good left ventricular function and antegrade flow around the aortic arch. Growth of left heart structures is well maintained with advancing gestational age. Sequential echocardiography is indicated during fetal life to monitor for progression of aortic valve stenosis, as some fetuses will demonstrate progressively increased severity of left ventricular outflow tract obstruction.

In severe cases of aortic stenosis diagnosed during fetal life, the left ventricle is typically dilated early in gestation with reduced systolic function (Figure 20.17, Video 20.8). Endocardial fibroelastosis is a frequent association, although the severity may vary. This appears as a bright echogenic lining of the left ventricular cavity. Mitral valve regurgitation may occur and, if severe, is associated with markedly dilated left atrium and poor prognosis (Figures 20.17 and 20.18, Videos 20.9 and 20.10) [58,59]. Often, retrograde flow can be seen in the transverse arch because antegrade flow across the aortic valve is inadequate (Figure 20.19). The interatrial communication, which normally permits right‐to‐left flow, may reverse due to left heart inflow obstruction. In some cases, the atrial septum may be highly restrictive or even intact (Figure 20.20). Doppler interrogation of the pulmonary veins, with particular attention to the degree and duration of flow reversal during atrial contraction, is extremely helpful in determining the degree of restriction of the atrial septum (Figure 20.21).

With advancing gestational age, growth of left heart structures is almost always limited so that by term, the aorta, left ventricle, and mitral valve are often severely hypoplastic. Judging which fetuses will be managed toward a biventricular circulation versus those that will be managed toward a single ventricle physiology is often difficult. The relative diameters and lengths of the right and left ventricles, presence of endocardial fibroelastosis, degree of mitral valve regurgitation, hypoplasia of the aorta, and direction of flow in the distal aortic arch may all help in prognostication [45]. Fetuses at the severe end of the spectrum will often require management with a single ventricle palliation using a Norwood strategy rather than balloon dilation of the aortic valve or surgical valvotomy. It is the progression of aortic valve stenosis to a situation analogous to hypoplastic left heart syndrome that has led to prenatal intervention being considered for affected fetuses [45–47]. The risks versus benefit of fetal cardiac intervention continues to be controversial but in recent years large international registries have been established to provide data to guide decision‐making in this regard [60].

The echocardiographic approach during fetal life includes all of the assessments listed earlier but in addition should also include:

• Diameters of left and right ventricles
  
• Lengths of right and left ventricles
  
• Diameters of the mitral and tricuspid annuli
  
• Severity of mitral valve regurgitation
  
• Diameters of aortic valve annulus and aortic arch
  
• Direction of systolic flow in the distal aortic arch (antegrade versus retrograde)
  
• Direction of flow across the atrial septum
  
• Flow profile in the pulmonary veins