Introduction
It is well recognized that obstruction within outflow tract of the morphologically left ventricle may be above the arterial valve, at the level of the valve itself, or in the subvalvar region. The arterial valve of the morphologically left ventricle, of course, although usually an aortic valve, can be a pulmonary valve when the ventriculoarterial connections are discordant. From the morphologic stance, the same lesions producing subaortic stenosis or regurgitation in the setting of concordant ventriculoarterial connections will produce obstruction to flow of blood to the lungs when the connections are discordant. However, the specific anatomic details of the latter lesions are discussed in the chapters devoted to the various clinical forms of transposition. Therefore this chapter is concerned with the lesions obstructing the morphologically left ventricular outflow tract in the setting of concordant ventriculoarterial connections.
Such congenital obstruction of the left ventricular outflow tract is said to account for 5% of all cardiac abnormalities. If all those possessing aortic valves with two leaflets were included in this number, the malformed aortic valve may represent the most common congenital cardiac malformation. It is difficult to determine the true incidence because aortic valves with two leaflets may not be recognized in childhood. Considered as a group, 75% of the patients with obstruction to outflow from the left ventricle will exhibit obstruction at valvar level. Apart from the 1 or 2 in each 100 with supravalvar obstruction, the remainder will have obstructive lesions below the level of the valve. The three forms may occur separately or together, and each may be associated with aortic regurgitation. Aortic regurgitation, irrespective of its cause, is discussed later in the chapter.
Morphology
Normal Aortic Root
To understand the mechanisms of obstruction at any level within the left ventricular outflow tract, it is necessary first to understand the normal arrangement. Most accounts remain based on the concept of an aortic “annulus,” albeit that this enigmatic entity is rarely described in consistent and satisfactory fashion. An “annulus,” if defined literally, is no more than a little ring. There are several rings within the normal aortic root, but none of them supports the leaflets of the aortic valve. The essence of normality is that the leaflets are hinged within the arterial root in semilunar fashion ( Fig. 44.1 ).
The root itself is formed by interlocking of the aortic valvar sinuses and the supporting ventricular structures. Because of the interlocking, there is a marked discrepancy between the locus of the hemodynamic, as opposed to the anatomic, ventriculoarterial junctions. The anatomic ventriculoarterial junction is the line over which the fibroelastic walls of the aortic sinuses are supported by the base of the left ventricle. The line is not nearly as well seen in the left ventricular outflow tract as in the right ventricular infundibulum. This reflects the fact that, as shown in Fig. 44.1 , it is only the leaflets supported by the two coronary arterial sinuses that have myocardium forming part of their bases. The noncoronary leaflet of the aortic root and the adjacent parts of the other two leaflets are supported by fibrous tissue formed by the continuity between the leaflets of the aortic and mitral valves. The rightward extent of this area of fibrous continuity also incorporates the membranous part of the ventricular septum (see Fig. 44.1 ). Nonetheless, as in the pulmonary root, the hemodynamic ventriculoarterial junction is marked by the semilunar lines of attachment of the aortic valvar leaflets (see Fig. 44.1 ). As a result, in addition to the myocardium incorporated into the bases of the coronary arterial valvar sinuses, fibrous triangles are incorporated at the distal extent of the ventricular outflow tract. The triangles extend distally to the level of the most distal attachment of the leaflets at the sinutubular junction. This structure is the most obvious ring in the left ventricular outflow tract, marking the line over which the expanded aortic sinuses become continuous with the tubular aorta. It marks the distal extent of the aortic root ( Fig. 44.2 ).
Because it is an integral part of the root and valvar competence depends on its integrity, it is somewhat illogical to describe stenosis at this level as being “supravalvar.” It is also illogical to consider only the peripheral attachment of the valvar leaflets to the sinutubular junction as the “commissures,” as is currently the usual practice. Defined literally, a commissure is a zone of apposition. Therefore, in addition to the peripheral ends of the zones of apposition, it is also necessary to recognize that the zone extends from periphery of the valvar orifice to its center ( Fig. 44.3 ). Competence of the valve depends on snug union of the leaflets along the full extent of these zones of apposition.
Furthermore, all parts of these zones need to open without hindrance if the valve is to function properly. There is one additional potential ring within the outflow tract. However, this ring is a virtual entity. It is made by creating a line that joins together the most proximal attachments of the three valvar leaflets within the left ventricle. It is this virtual basal ring that is usually identified by echocardiographers as the valvar annulus. The entirety of the root, considered in three dimensions, takes the form of a crown ( Fig. 44.4 ).
Therefore it follows that “annulus” does not seem the most obvious word with which to described the support provided for the valvar leaflets within the root. This is the more so because a majority of surgeons describe the semilunar remnants of the leaflets subsequent to the removal of their greater parts during operative procedures as the surgical “annulus.” The overall anatomic arrangement should be taken into account when measurements are made of the outflow tract. When diagrams are made to illustrate the concept of measurement of the “annulus,” they often show a line drawn between proximal points of attachment of the leaflets ( Fig. 44.5 , right ).
Such diagrams must involve a degree of poetic license on behalf of the observer because the section illustrated can never cut the full diameter of the arterial root (see Fig. 44.5 , left ). All of this normal anatomy is of relevance when considering the structure of stenotic lesions within the outflow tract, particularly the fact that so-called supravalvar stenosis involves tethering of the valvar leaflets at the level of the sinutubular junction.
Valvar Stenosis
The stenotic aortic valve is traditionally considered as showing unicuspid, bicuspid, or tricuspid patterns. Strictly speaking, a “cusp” is a point or elevation. Despite its popularity, it is not the ideal adjective to use when accounting for lesions of the abnormal valve. Our preference is to describe unifoliate, bifoliate, or trifoliate valves, according to the number of leaflets present. Nonetheless, we recognize that the abnormal valves will continue to be described in terms of cusps. However, when making such descriptions, it is necessary to take account also of the morphology of the valvar sinuses. This is because, when the curtain of leaflet tissue is compartmented to produce fewer than three component parts, the leaflet tissue itself remains suspended within three obvious sinuses. Examination of the so-called unifoliate and unicommissural valve from its the arterial aspect, for example, usually reveals a solitary slitlike opening within the valvar curtain ( Fig. 44.6A ). Careful examination also reveals the presence of raphes within the skirt of leaflet tissue, with examination from the ventricular side revealing the presence of three interleaflet triangles, albeit with two of them being vestigial.
Similarly, examination of the majority of the valves showing a bifoliate pattern of the leaflets ( Fig. 44.7 ) reveals that they are formed within a trisinuate prototype.
In the unifoliate, or unicommissural, valve (typically seen in infants with so-called critical stenosis), it follows that the keyhole opening within the valvar curtain represents the only properly developed zone of apposition (see Fig. 44.6 ). It is found between the hinges of the left and noncoronary aortic leaflets and “points” toward the mitral valve. Because of the vestigial nature of the putative zones of apposition between the other leaflets, they are abnormally attached to the ventricular wall in annular fashion. Therefore it is paradoxic that valvar leaflets possessing a ring-like attachment are likely to be stenotic or regurgitant. When seen in pathologic archives, the unicuspid and unicommissural valves are often housed in small fibroelastotic left ventricles, the hearts themselves fulfilling many of the anatomic criterions for inclusion within the hypoplastic left heart syndrome (see Chapter 69 ).
The bifoliate aortic valve is also often described in association with critical aortic stenosis, albeit again formed on a trisinuate prototype, but is also found in asymptomatic individuals. The leaflets themselves guard markedly dissimilar parts of the valvar orifice, with the larger leaflet formed by fusion of two putative leaflets, typically with a raphe showing the line of nonseparation between them (see Fig. 44.7 ). The conjoined leaflet usually represents either fusion of the two coronary leaflets (see Fig. 44.7 ) or fusion of the right and noncoronary leaflets. Truly bisinuate and bifoliate valves do exist but are rare, as are trisinuate but bifoliate valves without evidence of a raphe between the presumed conjoined leaflets. Stenosis, when it occurs, is the result of fusion of the ends of the zone of apposition between the two leaflets. Bifoliate valves can also produce problems when they become incompetent due to prolapse or if they provide a nidus for endocarditis. This is more likely to occur in adult life and is rarely seen in childhood. Stenosis producing problems in childhood can also be seen in the setting of a trifoliate valve, but more usually such valves are the seat of senile aortic calcification. When seen in childhood, the trifoliate valve, with dysplastic leaflets, is encountered most frequently in infants. A stenotic trifoliate valve is rare in older children and adolescents unless they have undergone previous surgery.
Calcification of the aortic valve can develop from the third decade in all patients with mildly stenotic or bifoliate valves. It may start as early as the second decade, particularly if the valves are dysplastic and myxomatous. However, most patients present in later life with severe calcific aortic stenosis in what was initially no more than a mildly stenosed valve or a valve with leaflets initially of markedly dissimilar size. The changes are more common in males than females. Patients with familial hypocholesterolemia, progeria, and rickets develop calcification earlier, even if the aortic valve is only mildly abnormal. Patients with bifoliate valves producing minimal stenosis usually do not develop calcific stenosis until the sixth or seventh decade, but presence of moderate or severe stenosis in childhood can lead to quite heavy calcification in the third and fourth decades.
Subvalvar Stenosis
A variety of lesions can obstruct the subaortic outflow tract, with or without a coexisting ventricular septal defect. When there is an interventricular communication, posterocaudal deviation of the muscular outlet septum is usually the most important lesion. This lesion is discussed in the chapters devoted to ventricular septal defect and interruption of the aortic arch. Obstruction can also be produced by hypertrophy of the ventricular septum, as seen in hypertrophic cardiomyopathy ( Chapter 61 ), by anomalous tissue tags derived from the membranous septum or the leaflets of the atrioventricular valves or by anomalous attachment of the tension apparatus of the left atrioventricular valve ( Fig. 44.8 ).
The last two lesions are also more likely to be found when there is a ventricular septal defect or in the setting of common atrioventricular junction and deficient atrioventricular septation. When the ventricular septum is intact, the most significant lesion is the subvalvar fibrous ridge, or diaphragm ( Fig. 44.9 ).
This lesion has been described in many ways. Although often termed “membranous,” almost always the lesion is a firm fibrous shelf that encircles the outflow tract, often extending to be attached also to the aortic valvar leaflets. The septal component of the obstructive lesion overlies the left bundle branch as it crosses the ventricular septum. A discrete plan of cleavage almost always exists between the shelf and the musculature. Because of this, it can readily be stripped away by surgery (see Fig. 44.9B ).
Because the lesion is acquired, there is always the likelihood of recurrence. The position can vary with regard to its proximity to the valvar leaflets. If extensive, it can produce tunnel stenosis. In florid cases, there is a marked abnormality in the alignment between the plane of the aortic root and the ventricular septum. This has been promoted as a potential cause of the malformation.
Supravalvar Aortic Stenosis
Supravalvar stenosis accounts for only 1% to 2% of cases of aortic stenosis seen in childhood. The condition may be familial or may be associated with disorders of calcium metabolism. The original description included failure to thrive, gastrointestinal upset, and mental retardation. The stenosis typically lies above the aortic sinuses and the coronary orifices but incorporates the sinutubular junction ( Fig. 44.10 ).
The aortic sinuses themselves are enlarged and bulge laterally, whereas the aortic leaflets are often slightly thickened and are disproportionately long in relation to the portion of sinutubular junction to which they are related. The coronary arteries, which take origin below the obstruction, are typically dilated, thick walled, and ectatic. The nature of the narrowing is variable. The most common form is the “hourglass” variety with dilation of the distal aorta (see Fig. 44.10 ). There are also diffuse or tubular varieties and, very rarely, a diaphragmatic or localized form. Irrespective of the type, the ascending aorta is usually grossly abnormal, with a thickened wall and disorganization of the media. The narrowing and scarring are not exclusive to the aorta and may be found in the iliac arteries and in the abdominal and renal vessels. Stenosis of the origin of the carotid and subclavian arteries, and less frequently the renal and mesenteric arteries, occurs in up to half the patients. The pulmonary circulation is also affected. In 20% of patients, there are multiple pulmonary arterial stenoses. These are mostly peripheral, being seen where the major vessels enter the lung. Consequently, supravalvar aortic stenosis in most, but not all, patients is part of a more widespread abnormality of the cardiovascular system involving the major conducting arteries. Histologic findings away from the site of the obstruction in the aorta show irregular thickening and branching of medial elastic fibers. This appearance has been dubbed a mosaic pattern or “higgledy-piggledy” arteriopathy.
Aortic Regurgitation
The stenotic aortic valve can also be regurgitant if the lesions producing stenosis also prevent the valvar leaflets coapting snugly during ventricular diastole. Isolated aortic regurgitation is much rarer than stenosis. If seen as an isolated finding in the neonatal period, reflux through an aorto–left ventricular tunnel should be excluded. In this entity, one of the valvar leaflets is suspended across the ventriculoarterial junction, so that blood is able to flow around the part that should be attached within the aortic root (see Chapter 51 ). Regurgitation can also be produced by abnormalities of the leaflets, such as perforations produced by infectious endocarditis or iatrogenic damage subsequent to balloon dilation. Dilation of the sinutubular junction will also prevent the valvar leaflets coapting, but this is an acquired rather than a congenital malformation ( Fig. 44.11 ).
Morphogenesis
We know that, as was the case for the pulmonary root (see Chapter 42 ), the aortic root develops within the intermediate component of the outflow tract. When initially formed, the outflow tract, which is supported above the cavity of the developing right ventricle, has myocardial walls to the margins of the pericardial cavity. It is at the margins of the pericardial cavity that the common lumen of the outflow tract becomes continuous with the cavity of the aortic sac, which gives rise to the arteries of the pharyngeal arches (see Chapter 3 ). By the time it becomes possible to recognize the potential site of formation of the arterial roots, the walls of the distal part of the outflow tract have been replaced by addition of nonmyocardial tissues from the second heart field. Growth of a protrusion from the dorsal wall of the aortic sac, developing between origins of the arteries of the fourth and sixth arches, divides the distal outflow tract into the intrapericardial components of the arterial trunks. Major outflow cushions are formed to separate the more proximal parts of the outflow tract, which retain their myocardial walls, into the aortic and pulmonary channels. As well as the major outflow cushions, there are additional intercalated cushions formed in the more distal part of the myocardial outflow tract. However, the component containing the intercalated cushions occupies the intermediate part of the overall outflow tract ( Fig. 44.12A ). It is in this intermediate component that the positioning of the intercalated cushions relative to the margins of the major cushions produces the primordiums of the arterial roots (see Fig. 44.12B ).
At the stage at which the roots begin to form, the outflow tract itself remains supported above the cavity of the right ventricle. It is not until embryonic day 13.5 in the developing mouse that the aortic root begins its transfer to the developing left ventricle. Concomitant with the transfer of the root, the initial embryonic interventricular communication becomes reoriented to form the entrance to the developing left ventricular outflow tract ( Fig. 44.13A ). As the aortic root achieves its transfer, a component of the proximal outflow tract myocardium is similarly transferred into the left ventricle, where it forms the summit of the parietal left ventricular wall. At the same time, the proximal outflow cushions themselves fuse with each other and muscularize, fusing at the same time with the crest of the muscular ventricular septum. This permits the tubercles from the ventricular aspects of the atrioventricular cushions to close the persisting embryonic interventricular communication, thus completing ventricular septation (see Fig. 44.13B ).
The parietal unfused margins of the distal outflow cushions have already begun to cavitate and separate away from the walls of the root while the root itself retains a location above the cavity of the right ventricle (see Fig. 44.13A ). As the cushions cavitate to form the leaflets, there is additional growth of nonmyocardial tissue from the second heart field to form the walls of the valvar sinuses. This growth of the nonmyocardial tissues continues up to term in the mouse, which takes place at the end of embryonic day 18.5. It is the nonmyocardial tissues that form the valvar sinuses, with the cushions cavitating so as to form the semilunar leaflets ( Fig. 44.14 ).
When initially transferred to the left ventricle, all three developing valvar leaflets are supported by proximal outflow tract myocardium. It is only at the end of embryonic day 15.5 in the mouse that the area between the nonadjacent, or noncoronary, leaflet becomes transformed into fibrous tissue. It has now been established that excessive fusion of the parietal margins of the major outflow cushions is the mechanism producing the bifoliate aortic valve with fusion of the two leaflets arising from the coronary arterial sinuses. This process has been demonstrated in a colony of Syrian hamsters. It has also been shown that mice with knockout of the eNOS gene develop bifoliate valves with fusion of the leaflets developed from the rightward of the major cushions and the intercalated aortic cushion. Therefore it can reasonably be presumed that excessive fusion of the major cushions, combined with fusion with the intercalated cushion, will produce the unifoliate and unicommissural variant. It is also currently known that cells derived from the neural crest populate the major cushions to form the valvar leaflets, with which the valvar sinuses are formed by tissues derived from the second heart field. However, the cells from the neural crest are less abundant in the aortic intercalated cushion. Evidence from other knockout mice suggests that failure of formation of the intercalated cushion produces a bifoliate valve that is also bisinuate.
Valvar Aortic Stenosis
Introduction
Valvar aortic stenosis is the most common type of left ventricular outflow tract obstruction. In the pediatric population, a congenitally malformed aortic valve (i.e., bicuspid or bifoliate aortic valve) is by far the most common cause of aortic stenosis. Rheumatic aortic stenosis due to fusion of the commissures with scarring and progressive calcification of the cusps is a less common cause in the high-income nations. Calcific degeneration of a tricuspid aortic valve is a common etiology for aortic stenosis in the older adult population.
Genetics and Epidemiology
A bicuspid aortic valve has an estimated prevalence in the general population of between 0.5% and 2%, making it the most common congenital heart defect. There is a male predominance of approximately 2:1 to 3:1. Bicuspid aortic valve is often associated with other congenital heart defects, most commonly with ventricular septal defect and other left-sided obstructive lesions, including interrupted aortic arch, coarctation of the aorta, hypoplastic left heart syndrome, and Shone syndrome with concomitant subvalvar aortic stenosis and mitral valve stenosis. Approximately 50% to 75% of patients with coarctation will have a bicuspid aortic valve ( Box 44.1 ).
Ventricular septal defect
Coarctation of the aorta
Interrupted aortic arch
Hypoplastic left heart syndrome
Subaortic stenosis
Mitral valve stenosis
The genetic determinants of bicuspid aortic valve are still not well defined. Certain genetic syndromes have a clear association with bicuspid aortic valve. Most notably, women with Turner syndrome, due to a complete or partial loss of a second X chromosome, have a prevalence of bicuspid aortic valve of greater than 20% to 30%. Bicuspid aortic valve is also more common in familial aortopathy syndromes including Loeys-Dietz syndrome, associated with pathogenic variants in the TGFBR1 and TGFBR2 genes, and certain forms of familial thoracic aortic aneurysm and dissection syndrome.
The genetics of nonsyndromic forms of bicuspid aortic valve appears to be more complex. Familial clustering is well recognized and suggestive of a mendelian pattern of inheritance. Studies report an incidence of bicuspid aortic valve or other left-sided obstructive congenital heart defects in 5% to 24% of first-degree relatives of patients with bicuspid aortic valve. In a prospective study of asymptomatic family members of patients with bicuspid aortic valve who underwent screening echocardiograms, 36.7% of the families had at least one additional family member with bicuspid aortic valve.
Variants in the signaling and transcriptional regulator gene NOTCH1 have been implicated in some familial cases of bicuspid aortic valve. The ACTA2 gene, which encodes for smooth muscle α-actin, has also been implicated in families with bicuspid aortic valve, along with a predisposition for aortic aneurysms and dissections. However, in the majority of cases of bicuspid aortic valve, no single-gene model clearly explains the inheritance, suggesting there are important multigenetic, epigenetic, and environmental modifiers that are responsible for the variable penetrance and phenotypic expression.
Progressive dilation of the thoracic aorta is a well-described complication in both syndromic and nonsyndromic forms of bicuspid aortic valve disease. Both the aortic sinuses of Valsalva and proximal ascending aorta above the sinotubular junction are larger compared with patients with normal trileaflet aortic valves. Mechanical factors related to the abnormal postvalvar turbulence in the setting of aortic stenosis have been implicated in the pathogenesis of aortic dilation, called poststenotic dilation. However, progressive aortic dilation has been documented even in patients with functionally normal bicuspid aortic valves, suggesting there is a genetic basis that results in an intrinsic structural developmental abnormality of the aortic wall. Histologically, the aortopathy in the setting of bicuspid aortic valve disease is similar to that of other familial aortopathies, such as Marfan syndrome, with fragmentation of elastin, loss of smooth muscles cells, and increase in collagen. However, the genetic basis for this aortic wall pathology, and its link to aortic valve morphogenesis in the setting of bicuspid aortic valve disease, is still not well understood.
Pathophysiology
Valvar aortic stenosis physiologically results in increased wall stress, or afterload, on the left ventricle. The left ventricle must generate a systolic pressure greater than aortic pressure to overcome the pressure load imposed by aortic stenosis during ejection. Chronic increase in left ventricular afterload from hemodynamically significant aortic stenosis, in turn, triggers compensatory structural changes characterized by concentric remodeling (reduction of the chamber diameter/wall thickness ratio) and hypertrophy (increase in mass) of the left ventricle. In accordance with Laplace’s law, concentric remodeling and hypertrophy of the left ventricle reduce wall stress and maintain cardiac output despite elevations in left ventricular systolic pressure.
On a cellular level, left ventricular hypertrophy results from an increase in protein synthesis and in the size and organization of sarcomeres within individual myocytes. However, recruitment of contractile elements occurs in parallel with fibroblast activation and leads to pathologic increases in cardiac extracellular matrix and fibrosis. Progressive hypertrophy also results in an imbalance between coronary supply and myocardial demands, resulting in microvascular and subendocardial ischemia that further contribute to myocardial fibrosis and myocardial dysfunction. Subendocardial ischemia may be exacerbated by a short diastolic coronary filling period that results from prolonged systolic ejection across a stenotic aortic valve, as well as from the tachycardia during periods of exercise. These pathologic fibrotic changes of the left ventricular myocardium can be detected by cardiac magnetic resonance imaging in patients with congenital aortic valve stenosis with evidence of variable degrees of late gadolinium enhancement.
Over time, if the degree of aortic stenosis is severe and not relieved by intervention, these compensatory mechanisms may fail. The wall thickness does not increase in proportion to the left ventricular systolic pressure. Subsequently, wall stress and afterload increases, resulting in progressive left ventricular chamber dilatation with concomitant increase in end-diastolic volume and pressure and eventually decreased contractility.
Clinical Features
Newborn/Infancy
The newborn or young infant presents in one of three ways. Newborns with critical aortic stenosis present with symptoms consistent with cardiogenic shock following closure of the arterial duct. The second mode of presentation is seen in neonates or young infants with left-sided cardiac failure but without dependency on the arterial duct to maintain systemic perfusion. In the third situation, patients may be referred for evaluation of a systolic murmur but are otherwise asymptomatic without signs of congestive cardiac failure.
Older Child
Older children, outside of the infancy period, are typically asymptomatic. These patients typically present when a murmur is detected during routine evaluation. Patients with moderate or severe aortic stenosis may present with complaints such as fatigue, exertional dyspnea, chest pain, and syncope. These symptoms result from the inability of the left ventricle to increase its output appropriately with exercise. Suspected aortic stenosis with these associated symptoms warrants urgent evaluation.
Physical Examination
Newborn/Infancy
Newborns who present with critical aortic stenosis are dependent on the patency of the arterial duct to sustain systemic cardiac output. They demonstrate features consistent with cardiovascular shock after spontaneous closure of the arterial duct within 1 week of age. These neonates are tachypneic and tachycardic. The physical examination reveals hepatomegaly, right ventricular enlargement, and diffusely weak pulses. A systolic ejection murmur may not be heard if there is severe left ventricular systolic dysfunction. A gallop rhythm may be noted. An ejection click is uncommon. If they have right ventricular hypertension and failure, they may have a systolic murmur of tricuspid valvar regurgitation.
Infants who present without ductal dependency can demonstrate physical exam findings consistent with left-sided cardiac failure. In this setting, the patients are tachypneic and have pulses that are usually low volume. Hepatomegaly may be present. Auscultatory findings may reveal an ejection click and a typical harsh crescendo-decrescendo systolic ejection murmur heard at the right upper sternal border. An associated thrill may be felt in the suprasternal notch even in mild valvar stenosis, but a parasternal thrill is typically felt only in severe obstruction.
Older Child
Physical exam findings in an older child can be similar to the asymptomatic infant with an ejection click and harsh crescendo-decrescendo systolic ejection murmur. Congestive cardiac failure is rare because, with time, patients are able to stabilize their left ventricular wall stress by increasing mass and thus preserving left ventricular systolic function.
The physical examination depends on the severity of the stenosis. The peripheral pulses are usually normal in those patients with mild, and even moderate, stenosis. Those with significant stenosis have low volume or plateau pulses. In some patients the right carotid and brachial pulses have a rapid upstroke when compared with the left-sided pulses. This is due to transmission of the impulse toward the brachiocephalic artery. A systolic thrill may be felt in the right infraclavicular region, over the carotid artery or suprasternal notch.
The first heart sound is normal and is frequently followed by a high-pitched ejection click, which is best heard at the lower left sternal border and may be maximal at the apex. This latter finding differentiates it from a click produced by the pulmonary valve, which is often lower pitched, heard along the upper left sternal border with respiratory variation in intensity (louder during expiration). Clinical cardiomegaly is uncommon in the absence of associated aortic regurgitation.
Investigations
Electrocardiogram
The electrocardiogram is usually normal or may demonstrate evidence of left ventricular hypertrophy, depending on the severity of the stenosis. These changes include increased voltages in the left precordial leads, with or without strain pattern characterized by T wave inversions and associated ST segment depression in the inferolateral leads. Despite these common findings, left ventricular hypertrophy and strain pattern is neither highly sensitive nor highly specific for severe stenosis. The presence of Q waves in the left precordial leads is uncommon and may suggest associated lesions. The electrical axis is usually normal.
Chest Radiograph
Patients who present with critical aortic stenosis in the neonatal period or severe aortic stenosis in infancy may have radiographic findings consistent with cardiomegaly with enlargement of the left heart borders and pulmonary edema. The majority of older asymptomatic patients will have an unremarkable chest radiograph with normal cardiothymic silhouette. Dilation of the ascending aorta and calcification of the aortic valve may be evident on radiograph in older adult patients.
Echocardiogram
Transthoracic echocardiogram is currently the mainstay for serial assessment and decision-making in children with aortic valve disease. The valvar morphology is best seen from the parasternal short-axis view ( Figs. 44.15 and 44.16 ; ), where the number of leaflets and their zones of apposition can be seen. The parasternal long-axis view is used for assessment of leaflet mobility, as well as measurement of the left ventricular outflow tract and aortic valve annulus, which can have variable degrees of hypoplasia (see Figs. 44.15 and 44.16 ; through ).
The degree of aortic stenosis can be quantified by echocardiography in different ways. In pediatrics, the Doppler-derived measurements of the flow velocity, as well as the calculated maximum instantaneous and mean pressure drop, across the aortic valve are the primary methods used to determine the severity of aortic stenosis. The gradients are derived from continuous wave Doppler interrogation of flow across the left ventricular outflow tract in the apical, suprasternal, and high right parasternal locations, and the highest velocity spectral Doppler is typically used ( Fig. 44.17 ). These measurements are also used as part of decision-making on timing for intervention, in conjunction with left ventricular function and clinical symptoms. The degree of stenosis is a continuum that extends from those without hemodynamic significance to severe obstruction of flow. The current recommendations of grading aortic stenosis severity are shown in Table 44.1 .
| Aortic Stenosis Severity | Jet Velocity (m/s) | Mean Pressure Gradient (mm Hg) |
|---|---|---|
| Mild | 2.0–2.9 | <20 |
| Moderate | 3.0–3.9 | 20–39 |
| Severe | >4.0 | >40 |
Alternatively, echocardiography can be used to estimate the area of the orifice of the stenotic valve, which is also used to categorize the severity of stenosis. In the pediatric and young adult population, absolute pressure gradients are preferred over valve orifice area in assessing the degree of aortic stenosis, primarily due to practical limitations with the measurements and calculations involved in valve orifice area that are magnified in the pediatric population.
A thorough evaluation by echocardiography of associated cardiac defects is important, especially in the neonate and infant with severe aortic stenosis. Associated defects include endocardial fibroelastosis, mitral valve abnormalities, coarctation of the aorta, and ventricular septal defects ( Fig. 44.18 ). These associated defects can impact both timing and type of intervention. Due to risk for progressive dilation of the ascending aorta, individuals should also have serial echocardiograms to track the dimensions of their aorta and compare the results to age-matched controls.
Magnetic Resonance Imaging
The role of cardiac magnetic resonance imaging in the assessment of aortic stenosis is to identify the level of obstruction, determine its mechanism, assess the ascending aortic dimension, and evaluate for associated aortic insufficiency. This can be a useful tool, particularly in older patients, if echocardiographic evaluation is suboptimal due to difficult imaging windows. The use of cardiac magnetic resonance also can provide an accurate evaluation for myocardial fibrosis by quantifying late gadolinium enhancement.
Cardiopulmonary Exercise Testing
Older children and adolescents with aortic valve stenosis are at risk for exercise-associated symptoms and even sudden death. As described previously, with progressive valvar obstruction, left ventricular hypertrophy and an imbalance between coronary supply and myocardial demands can result in microvascular and subendocardial ischemia. During exercise the pressure within the left ventricle rises and increases oxygen demand, while the associated tachycardia results in reduced diastolic coronary filling. This results in a myocardial oxygen supply and demand mismatch. This may give rise to myocardial ischemia and potential for malignant dysrhythmias and sudden death.
Exercise stress testing has long been correlated with disease severity in patients with aortic stenosis, but the primary role is the evaluation and risk stratification of asymptomatic patients with severe disease. Symptom-limiting stress testing has been shown to be safe in patients with severe aortic stenosis, and normal results predict a decreased risk in adverse cardiac events when compared with abnormal findings. Exercise testing may be considered in asymptomatic patients to ensure that they can tolerate desired physical activities with the absence of symptoms, exercise-induced hypotension, or ischemia. Symptomatic patients with severe aortic stenosis should avoid testing.
Cardiac Catheterization
Due to advances in noninvasive imaging, cardiac catheterization is used primarily for intervention rather than for diagnosis. However, it can be used selectively for invasive hemodynamic measurements when noninvasive tests are inconclusive or when there is a discrepancy between noninvasive tests and clinical findings regarding the severity of aortic stenosis ( Fig. 44.19 ).
Natural History
Valvar aortic stenosis has a wide spectrum of anatomic and clinical variations. Critical aortic stenosis in newborns and infants represents a distinct and challenging group with severe obstruction at the valvar level and ductus-dependent systemic circulation. They may become severely ill when the ductus closes, manifesting with low cardiac output, inadequate systemic perfusion, and severe metabolic acidosis.
Most patients, especially those with bicuspid aortic valves, will remain asymptomatic during childhood. Over time, the leaflets become thickened and fibrotic, resulting in progressive aortic stenosis. If untreated, chronic severe aortic valve stenosis will result in symptoms of exercise intolerance and risk for complications such as congestive heart failure and sudden death.
The rate of progression of aortic stenosis can be highly variable. Patients who were diagnosed at a younger age and/or had a higher degree of stenosis at the time of presentation typically have more rapid progression. However, the majority of children with bicuspid aortic valve will remain asymptomatic, with only 1 in 50 having clinically significant valve disease by adolescence. Due to progressive calcification and/or thickening of bicuspid aortic valves overtime, the majority of patients develop significant valve stenosis and/or regurgitation by the fourth and fifth decade of life.
Younger age and higher degree of aortic stenosis at the time of diagnosis are risk factors for more rapid progression and need for intervention. In the Joint Study of the Natural History of Congenital Heart Defects, patients presenting with aortic stenosis at younger than 2 years were more likely to have progression and 68% ultimately required surgical intervention during the 4- to 8-year follow-up period. In the long-term follow-up study of this same cohort, those patients who originally had a mild degree of stenosis, with catheter-derived aortic valve gradients less than 25 mm Hg, had a 20-year freedom from aortic valve surgery of 87%, which was significantly higher than 38% freedom from surgery in those patients with original gradients greater than 50 mm Hg.
Chronic severe aortic valve stenosis may be tolerated without overt symptoms, but eventually as the left ventricle decompensates, symptoms of angina, syncope, or heart failure can develop. After the onset of symptoms, the average survival is 2 to 3 years, with a higher risk of sudden death relative to asymptomatic patients. Sudden death occurred in 5% of the Natural History Study cohort and was related to severity of valve stenosis and previous history of valve intervention. However, in a more recent study of more than 500 patients with congenital aortic stenosis, sudden death was an uncommon event with an estimated incidence of 0.18 per 1000 patient years. In a longitudinal study of 622 adults with asymptomatic but hemodynamically severe aortic stenosis followed for up to 5 years, sudden death occurred at a rate of 1% per year.
Endocarditis is also a well-known complication in patients with bicuspid aortic valve. The Second Joint Study of the Natural History of Congenital Heart Defects estimated the risk for endocarditis of 0.27% per year for patients with congenital aortic valve stenosis, which was 70-fold higher than the general population. A more recent population-based study of Olmstead County, Minnesota estimated the incidence of endocarditis of patients with native bicuspid aortic valves of 9.9 per 10,000 patients years, which was 16.9 times higher compared with the general population.
Management of Critical Aortic Stenosis
Medical Management
Critically ill neonates are stabilized by aggressive resuscitation (ventilatory and inotropic support, correction of acidosis, and protection of multiorgan function), while patency of the arterial duct is maintained by prostaglandin E1 infusion. A trial discontinuation of prostaglandins should be undertaken. Intervention (balloon valvuloplasty or open valvotomy) is indicated on a semielective basis if ductal closure is tolerated. However, dependency on the ductal circulation is a clear indication for neonatal intervention. Young infants with severe symptomatic aortic stenosis resulting in heart failure, respiratory insufficiency, or poor growth may also require inotropic medications and diuretics prior to aortic valve intervention.
Timing of Intervention
In the neonate with critical aortic stenosis and ductal-dependent systemic circulation, there may be varying degrees of hypoplasia of the left ventricle and other left heart structures. The key issue in this population is to decide whether left-sided structures are adequate to sustain the systemic circulation and, if so, what kind of treatment is the most beneficial. Studies have proposed formulas incorporating preoperative clinical and echocardiographic features that could predict which subjects with multiple small left heart structures may have improved survival with a Norwood stage 1 single ventricle palliation compared with a biventricular repair that would include aortic valvotomy. Neonates with critical left ventricular outflow tract obstruction who underwent biventricular repair but were predicted to have a survival advantage with single ventricle palliation had worse outcomes, including early need for reintervention and higher mortality.
Factors that would suggest improved outcomes with single ventricle palliation include significant mitral and/or aortic annulus hypoplasia, ratio of left and right ventricular lengths less than 0.8, a cardiac apex not formed by the left ventricle, and presence of endocardial fibroelastosis. Predominantly retrograde flow in the ascending aorta is suggestive of severely hypoplastic left heart structures and most often a single ventricle palliation will be necessary; however, the presence of total or predominant antegrade blood flow in the ascending aorta and transverse aortic arch correlates with survival after a biventricular type of repair.
Catheter Intervention
At many centers, transcatheter balloon aortic valvuloplasty is considered first-line treatment for critical aortic valve stenosis. Ballooning relieves aortic stenosis by causing a rupture along the lines of least resistance, either along the underdeveloped commissures or into the cusp tissue.
Early mortality in critical aortic stenosis after balloon valvuloplasty is between 9% and 14%. Compared with surgical aortic valvotomy for critical aortic stenosis, balloon valvuloplasty was associated with greater reduction in the degree of stenosis but resulted in higher risk for aortic regurgitation. The incidence of moderate or severe aortic regurgitation shortly after balloon valvuloplasty is reported to be between 7% and 33%. However, the survival and freedom from reintervention at 5 years were similar between the surgical and transcatheter aortic valve intervention groups. Adverse events after balloon intervention include a 15% incidence of aortic wall injury, a 2.6% incidence of procedural femoral artery damage, and a 5% incidence of injuries to the heart itself, such as rupture of the valves or myocardial perforation.
Surgical Intervention
New surgical techniques have increased the enthusiasm for open surgical valvotomy as the primary intervention in patients with critical aortic stenosis. Open surgical valvotomy allows construction of a cusp anatomy that is as close as possible to the normal anatomy, potentially allowing for a more durable aortic valve repair. Shaving of thickened cusps, excision of obstructive myxomatous nodularities, and mobilization of the cusps effectively increase the orifice area of the valve in any type of morphology, with a minimal risk of creating regurgitation. If commissural posts are developed, tricuspidalization of the valve is usually possible, thus preserving the native aortic valve in the majority of patients in the long run. Surgical intervention also has the advantage of addressing associated cardiac lesions at the same time ( ).
Early mortality after open valvotomy is reported to be between 6% and 19%. Overall survival is between 70% and 90% at 1 year and usually remains unchanged at 5 years and 10 years of follow-up. The 10-year event-free survival for critical neonates is between 50% and 70%. These figures compare favorably with the 29% to 54% event-free survival at 10 years reported after balloon valvotomy.
Hybrid Approach
A hybrid procedure that incorporates both catheter and surgical modalities serves as a bridge to a more definitive repair for patients with a borderline left ventricle and/or depressed left ventricular function. A hybrid approach may involve some combination of bilateral pulmonary banding, enlargement of the atrial septal communication to decompress the left heart, maintain patency of the arterial duct, and either a balloon or surgical aortic valvotomy ( ). This concept may significantly reduce the risk of a definitive procedure by providing patients more time to recover, mature, and “declare themselves” as either one- or two-ventricle candidates.
Long-Term Outcomes
Both balloon valvotomy and open valvotomy are firmly established as effective initial treatments, with encouraging survival benefits. Mortality is associated with hypoplasia of the left heart structures and the presence of endocardial fibroelastosis. However, both methods are palliative procedures and reintervention is likely. Although patients undergoing open valvotomy are more likely to have residual stenosis, those undergoing balloon valvotomy are more likely to develop progressive insufficiency. Tricuspid valve morphology showed superior long-term outcomes of open valvotomy in comparison with balloon valvotomy regarding preservation of the native aortic valve.
Management of Noncritical Aortic Stenosis
Medical Management
In the older child or adolescent with asymptomatic valvar aortic stenosis, there are no medical therapies that are proven to prevent or delay the progression of stenosis or need for intervention. Treatment of hypertension, if present, is reasonable to reduce the overall afterload on the left ventricle; however, medications for afterload reduction are not indicated in normotensive patients. There is theoretical concern that afterload reduction may precipitate a decrease in cardiac output in the setting of hemodynamically significant aortic stenosis. Antihypertensives, if indicated, should be started at a low dose and gradually titrated up as needed until patients are normotensive.
Lipid-lowering therapy with statin medications has been studied in adults with valvar aortic stenosis with a goal of reducing cusp calcification and hemodynamic progression. However, several prospective randomized controlled trials have not demonstrated benefit with statins with regards to disease progression, and therefore they are not recommended for routine management in patients with valvar aortic stenosis.
Due to risk for sudden death with exercise, activity restrictions should be considered in patients with severe aortic stenosis. The most recent statement from the American Heart Association and American College of Cardiology recommends that patients with severe aortic stenosis be restricted from competitive athletics and participate only in low-intensity activities. Those with mild or moderate aortic stenosis can participate in all competitive sports as long as they have no symptoms with exercise, less than or equal to mild left ventricular hypertrophy, absence of left ventricular strain pattern on electrocardiogram, and normal maximum exercise stress test without evidence of ischemia, arrhythmias, or drop in blood pressure.
Although patients with bicuspid aortic valve are at risk for endocarditis, antibiotic prophylaxis is not recommended prior to dental work or other procedures. However, patients should be counseled on the importance of good oral and skin hygiene to reduce the risk of bacteremia from daily activities.
Timing of Intervention
For asymptomatic children and young adults with severe aortic valve stenosis, the indications and timing for aortic valve intervention are not well defined ( Box 44.2 ). Surgical timing is based on weighing the relative risks of no intervention (i.e., risk of congestive heart failure and sudden death) versus the risks associated with the procedure (catheter or surgical).
