Congenital aortic stenosis: Congenital aortic regurgitation

Congenital aortic stenosis

Normal aortic valves are composed of a connective tissue framework of interstitial cells and a matrix covered by endothelial cells. During valvulogenesis, extracellular matrix proteins direct cell differentiation and cusp formation. Five varieties of congenitally abnormal aortic valves are based on the number and types of cusps and commissures ( Box 7.1 ). A unicuspid aortic valve is either acommissural or unicommissural. A unicuspid acommissural valve is characterized by a single leaflet with a central orifice that is usually stenotic, but can be stenotic and regurgitant. Traces of three rudimentary commissures do not divide the valve ( Fig. 7.1 A , left upper ). This type of congenitally stenotic semilunar valve is found in the pulmonary location (see Chapter 10 ) but rarely in the aortic location. A unicommissural unicuspid valve is characterized by a single commissural attachment to the aorta (see Fig. 7.1 A , left middle , and Fig. 7.2 ). ^, The single (unicuspid) leaflet originates from a single commissural attachment, proceeds across the aortic orifice without making contact with the aortic wall, bends on itself, and returns to reinsert at the same attachment site from which it originated. ^, Remnants of rudimentary raphes are occasionally present. Viewed from above, the orifice resembles an exclamation point (see Fig. 7.1 A , left middle ). The typical unicommissural valve is intrinsically stenotic, but if the free edge is sufficiently redundant and the single commissure is not fused, obstruction is initially absent but subsequently appears when mobility is reduced by fibrosis and calcification.

A bicuspid aortic valve is the commonest congenital anomaly to which that structure is subject (see Fig. 7.1 A , left lower group , and Fig. 7.3 ) ^{, ,} and is the commonest gross morphologic congenital abnormality of the heart or great arteries in adults. Estimated frequency in the general population has been reported as 0.5% to 0.6% and 0.9% to 1.36% with an overall prevalence in the United States of approximately four million. ^, The male/female ratio is 2:1. The bicuspid aortic valve is a genetic disorder, with a transmission pattern suggesting autosomal dominant inheritance. ^, There is a low prevalence of bicuspid aortic valve in African American. Acquired calcification of a congenitally bicuspid aortic valve accounts for approximately half of surgical cases of isolated aortic stenosis in adults. ^, Hypercholesterolemia is an atherosclerotic risk factor for the development of calcification. In bicuspid aortic valve , differentiation of mesenchymal cells into mature aortic valve cells correlates with the expression of the matrix protein fibrillin-1, which is deficient in bicuspid aortic valve tissue. In some embryos, the aortic intercalated valve swelling is displaced proximally, giving rise to a bicuspid aortic semilunar valve more distally, suggesting variations in the structure of the outflow tract of the human embryonic heart may contribute mechanistically to the occurrence of the bicuspid aortic valve.

Three morphologic types of a bicuspid aortic valve based on cusp size are characterized by two cusps of equal size, two cusps of unequal size, and a conjoined cusp twice the size of its nonconjoined mate. Three morphologic types based on commissural fusion are characterized by fusion of the right and left coronary cusps (most common), fusion of the right and noncoronary cusps, and fusion of the left and noncoronary cusps (least common). A false raphe can be well formed, fenestrated, calcified, or absent. ^, If the free edges of the bicuspid leaflets are sufficiently long, if the cusps are thin and mobile, and if the commissures are not fused, the valve is functionally normal—unobstructed—which is the usual condition at birth (see Fig.7.1 A, left lower ). ^{, ,} Conversely, if the commissures are congenitally fused, or if the free edges of the cusps are not longer than the diameter of the aortic ring, the valve is inherently obstructed (see Fig. 7.1 A, left lower ). Fusion of the right and left coronary cusps is strongly associated with coarctation of the aorta. Fusion of the right and noncoronary cusps is associated with valve pathology. Sclerosis of a bicuspid aortic valve begins as early as the second decade and calcification as early as the fourth decade. The fibrocalcific process is more rapid in bicuspid aortic valves with cusps of unequal size because of maldistribution of tension during diastolic closure. Bicuspid aortic and bicuspid pulmonary valves are not known to coexist in humans.

A functionally normal bicuspid aortic valve can continue to function normally throughout a long lifetime, but more often than not, fibrocalcific thickening or acquired commissural fusion decrease mobility and render the valve stenotic (see Fig. 7.1 A , left lower group , and Fig. 7.4 ). ^{, ,} Abnormal mechanical stress is an important factor in promoting fibrosis and calcification of a bicuspid bicommissural aortic valve (see Figs. 7.3 and 7.4 ). An important consequence of a functionally normal bicuspid aortic valve is progressive regurgitation that may be accelerated by infective endocarditis to which a bicuspid valve is highly susceptible (see later). Rarely, a severely incompetent bicuspid aortic valve becomes stenotic with virtual loss of regurgitation.

Dilation of the ascending aorta is consistently associated with a congenitally bicuspid aortic valve (see Figs. 7.1 C, 7.3 , and 7.4 ), but the term post stenotic dilation is a misnomer because the ascending aorta may be dilated whether the bicuspid valve is stenotic, incompetent, or functionally normal. Dilation is due to an inherent medial abnormality that expresses itself as an ascending aortic aneurysm with chronic aortic regurgitation (see Fig. 7.4 ) or dramatically as a dissecting aneurysm. A decrease in ascending aortic elasticity is independent of dilation. ^, Aortic dilation associated with a bicuspid aortic valve relates to sex, hemodynamics, and valve morphology. On a bicuspid aortic valve, predominant aortic regurgitation appears more prevalent in males, while predominant aortic stenosis is more common in females. Aortic regurgitation has been shown to be more associated with diffuse aortic enlargement extending to the ascending aorta, whereas moderate-severe aortic stenosis seems more confined to the ascending aorta. In addition, male sex and right-left cusp pattern of cusp fusion seem associated with larger proximal aortic root diameters.

Trileaflet aortic valves are congenitally abnormal when three cusps and three commissures are miniaturized within a small aortic ring or when an aortic valve is the site of myxoid dysplasia. In a hydraulically ideal aortic valve with three equal cusps, diastolic force is equally distributed among the three cusps and their sinus attachments. Cuspal inequality is a common variation of normal in trileaflet aortic valves but results in unequal distribution of diastolic force (see Fig. 7.1 B). ^, The fibrocalcific process of aging proceeds more rapidly in the cusp or cusps that bear the greatest hemodynamic stress. ^, Accordingly, cuspal inequality in a normal trileaflet aortic valve enhances the aging process, converting a functionally normal trileaflet valve into fibrocalcific aortic stenosis. ^, Similarly, the tendency for a bicuspid aortic valve to become fibrocalcific (see Fig. 7.2 C) is related in part to the mechanical stress inherent in bicuspid cuspal inequality (see Fig. 7.2 B). The quadricuspid aortic valve, first reported in 1862, can function normally or cause incompetence (see Figs. 7.33 and 7.40 , later) but is rarely stenotic. Six-cuspid semilunar valves sporadically occur with truncus arteriosus (see Chapter 25 ).

Fixed subaortic stenosis is the second most common variety of congenital obstruction to left ventricular outflow ^, and accounts for 15% to 20% of all types of congenital aortic stenosis. It occurs in isolation ( Fig. 7.5 ) or with other congenital cardiac defects. ^, Nonfixed muscular subaortic stenosis can coexist with severe aortic valve stenosis and can account for as much as half of the pressure gradient.

This chapter deals with two principal varieties of fixed subaortic stenosis in hearts that are otherwise devoid of congenital heart disease. The first variety is characterized by a thin fibrous crescent-shaped membrane located immediately beneath the aortic valve (see Fig. 7.5 A). ^, The membrane is occasionally relatively thick and forms a fibrous or fibromuscular collar that extends across an otherwise normal left ventricular outflow tract and inserts onto the anterior mitral leaflet. This form of fixed subaortic stenosis occurs in human hearts as well as in dogs, pigs, and cows. The aortic root is not dilated. Aortic regurgitation is associated with malformed leaflets that are damaged by the proximity of the subvalvular membrane or fibromuscular collar and by the impact of the eccentric systolic jet (see Fig. 7.5 B). Tubular subaortic stenosis is a less common variety of fixed obstruction to left ventricular outflow and is represented by a fibromuscular channel that occupies several centimeters within the outflow tract ( Fig. 7.6 ). ^{, ,} A layer of fibrous tissue extends onto the ventricular surface of the anterior mitral leaflet. The aortic cusps show fibrous thickening as with discrete subaortic stenosis. The aortic root is not dilated (see Fig. 7.6 ). ^,

Fixed subaortic stenosis as just defined is not present during intrauterine cardiac morphogenesis is therefore not con genitus , and accordingly is uncommon if not rare in neonates and infants. The disorder becomes manifest after the first year of life and then changes in both severity and morphology. In contrast to rapid progression in infants and children, fixed subaortic stenosis in adults progresses slowly. ^{, , ,} Aortic regurgitation is common but is usually mild and nonprogressive (see Fig. 7.5 B).

Supravalvular aortic stenosis is the least common variety of congenital obstruction to left ventricular outflow . The most frequent type is a localized segmental hourglass deformity immediately above the aortic sinuses with medial thickening and fibrous intimal proliferation ( Fig. 7.7 A). The size of the aorta distal to the obstruction is normal or reduced. The sinuses of Valsalva are enlarged. Localized supravalvular aortic stenosis is occasionally caused by a fibrous membrane with a central opening. An uncommon variety is represented by tubular hypoplasia of the ascending aorta beginning above the sinuses of Valsalva and associated with narrowing of the orifices of the brachiocephalic arteries (see Fig. 7.7 B). ^, The aortic leaflets are usually thickened and adherent to the supravalvular stenosing ridge, ^, are occasionally dysplastic, and may fuse to a coronary ostium. The aortic valve abnormalities usually cause no more than mild regurgitation.

Three additional features of supravalvular aortic stenosis include: (1) the anatomy of the extramural coronary arteries , (2) the condition of the aortic leaflets and aortic sinuses , and (3) the association with Williams syndrome. Obstruction of a coronary ostium can be caused by adherence of a distorted aortic leaflet to the supravalvular stenotic ridge, by aortic medial proliferation, and by the supravalvular ridge itself that can impede diastolic flow into an ostium. Because the coronary ostia are proximal to the supravalvular obstruction, the coronary arteries are exposed to elevated left ventricular systolic pressure and become thick-walled and dilated (see Fig. 7.7 ). Coronary artery aneurysms have been described, and hypertension is a risk factor for premature atherosclerosis.

In 1961, Williams et al. described the association of supravalvular aortic stenosis with distinctive elfin facies and mental retardation. In 1962 and 1964, Beuren and coworkers expanded the syndrome to include pulmonary artery stenosis. Williams syndrome or Williams-Beuren syndrome now includes elfin facies, mental retardation, small stature, infantile hypercalcemia, supravalvular aortic stenosis, pulmonary artery stenosis, and important vascular abnormalities, especially in adults. ^, Renal abnormalities occur in nearly half of afflicted patients and are represented by renal artery stenosis, segmental scarring, cystic dysplasia, nephrocalcinosis, marked asymmetry in kidney size, solitary kidney, and pelvic kidney. ^, Systemic hypertension is not necessarily related to the renovascular abnormalities but instead is related to the stiffness of arterial walls. A generalized arteriopathy is characterized by medial thickening and luminal narrowing of systemic and pulmonary arteries. Long segment narrowing of the aorta may occur with or without localized coarctation. Involvement of cerebral arteries is responsible for strokes. Tortuous retinal arteries similar to those that accompany coarctation of the aorta (see Fig. 8.8 in Chapter 8 ) were described in the original report of Williams and Barratt-Boyes, and in 1985, the observation was confirmed.

The physiologic consequences of congenital aortic valve stenosis are reflected in the response of the left ventricle to increased afterload. An adaptive increase in left ventricular mass in the immature heart is due chiefly to hyperplasia (replication) of cardiomyocytes. In contrast, the increase in left ventricular mass in the mature heart is due to hypertrophy (an increase in cell size) of terminally differentiated cardiomyocytes. The afterloaded immature heart is capable of capillary replication that is proportional to cardiomyocyte replication, so capillary density remains normal and coronary flow reserve remains normal. ^, The increase in left ventricular mass characterized by myocyte hyperplasia with proportionate growth in the microvascular bed sets the stage for low left ventricular systolic wall stress and supernormal ejection performance. The left ventricle thickens concentrically, and the cavity size is normal or small, so distensibility decreases. A greater force of left atrial contraction generates the end-diastolic fiber length necessary for left ventricular performance appropriate for the increased afterload without an increase in end-diastolic volume or left atrial mean pressure. The normal trileaflet aortic valve and its annulus increase in anatomic cross-sectional area with age even after maturity. The normal trileaflet physiologic orifice, which is the cross-sectional area defined by the leaflets in systole, is flow dependent, varying directly with the volume and rate of left ventricular ejection. In the resting state, less than half the cross-sectional area of a normal trileaflet aortic valve is utilized during ejection, so a large reserve is available during high flow states.

The subendocardium of the left ventricle in aortic stenosis is vulnerable to ischemia because of a selective decrease in perfusion. In neonates and infants with severe aortic stenosis, subendocardial ischemia is responsible for papillary muscle infarction with mitral regurgitation and is responsible for endocardial fibrosis and reduced cavity size that depress left ventricular contractility. A progressive rise in left ventricular filling pressure, in left atrial mean pressure, and in pulmonary arterial pressure provokes right ventricular failure. Supravalvular aortic stenosis incurs the additional impediment of compromised coronary perfusion (see earlier).

The physiologic response of the neonate to severe aortic stenosis is best understood in light of the fetal circulation. Intrauterine left ventricular volume is low because pulmonary blood flow is virtually nil. When lungs expand at birth, pulmonary blood flow commences, and a severely obstructed, thick-walled left ventricle with reduced cavity size suddenly receives a sizable increment in volume. Left ventricular filling pressure rises steeply, left atrial pressure rises in parallel, and a left-to-right shunt is established across a stretched valve-incompetent foramen ovale. If a small left ventricular cavity is beset with endocardial fibrosis or fibroelastosis, the hemodynamic consequences are correspondingly worse. Vasoreactive pulmonary arterioles constrict, pulmonary artery pressure rises, and pressure overload is imposed on an already volume-overloaded right ventricle. Temporary patency of the ductus arteriosus diverts right ventricular blood into the aorta and delays the onset of symptoms, but when the ductus closes, that advantage is lost because the entire right ventricular output enters the pulmonary circulation and the left side of the heart.

The response to dynamic exercise mild aortic stenosis is normal, but when stenosis is severe, left ventricular stroke volume is blunted at each level of graded isotonic stress. In congenital aortic valve stenosis, the augmented flow and increased left ventricular systolic pressure induced by exercise result in a larger computed aortic valve area, implying that the stenotic valve is sufficiently mobile to open more widely when stressed. Activation of canine left ventricular baroreceptors in response to an increase in left ventricular pressure or stretch induces hypotension due to skeletal muscle vasodilatation. Reflex vasodilatation and bradycardia induced by activation of left ventricular baroreceptors during isotonic exercise are responsible for hypotension and exertional syncope.

Physical appearance

Williams syndrome (nonfamilial supravalvular aortic stenosis) is characterized by peculiar facies, short stature, and mental retardation. ^{, ,} The chin is small (hypoplastic mandible), the mouth is large, the lips are patulous, the nose is blunt and upturned, the eyes are widely set with occasional internal strabismus, the cheeks are baggy ( Fig. 7.8 ), the teeth are malformed, and the bite is abnormal (malocclusion) ( Fig. 7.9 ). Flat molar regions accentuate the prominence of a wide mouth with full lips, small jaw, and long philtrum. The brow is broad with prominent supraorbital ridges. The nasal tip is broad and the nacres are anteverted. Adults with Williams syndrome are relatively short and tend to have lordosis, kyphoscoliosis, and joint abnormalities of the lower limbs that result in a stiff awkward gait. Friendly temperaments and deep somewhat metallic voices further emphasize the similarities. XO Turner syndrome (see Chapter 8 ) represents another distinctive physical appearance that coexists with a bicuspid aortic valve. Congenital heart disease with Turner syndrome has been known since the initial description by Morgagni and is coupled with different patterns of X monosomies. Abnormal karyotypes consist of 45 X mosaicism and X structural abnormalities. Patients with severe dysmorphic features have a significantly higher prevalence of congenital heart disease, and 45 X Turner patients have the highest prevalence. X structural abnormalities are associated with an increased prevalence of bicuspid aortic valve, but with X deletion, the incidence of congenital heart disease is not increased. In Turner syndrome, aortic dissection may occur in young individuals at smaller aortic diameters than in the general population or other forms of genetically triggered aortopathy. However, aortic dissection in Turner syndrome may occur even in the absence of cardiac malformations or hypertension. In Noonan syndrome (Turner phenotype with normal genotype), obstruction to left ventricular outflow is due to hypertrophic obstructive cardiomyopathy ( Fig. 7.10 ).

The arterial pulse

The pulse pressure is small, the rate of rise is slow, the peak is sustained, and the decline is gentle ( Figs. 7.11 and 7.12 ). This typical configuration is not as frequent in children as in adults with equivalent aortic stenosis. ^, Children with severe obstruction may have a brachial arterial pulse that is interpreted as normal, although palpation of the carotid artery improves accuracy. ^, A bisferiens pulse (twin peaked) implies coexisting aortic regurgitation.

The right and left brachial and carotid arterial pulses are symmetric in valvular or fixed subvalvular aortic stenosis, but in supravalvular aortic stenosis, the rate of rise, the systolic pressure, and the pulse pressure are greater in the right brachial artery and in the right carotid artery (see Fig. 7.12 ) ^, because the hourglass deformity directs the high-velocity jet toward the right wall of the aorta, and the Coanda effect (affinity of a jet stream for adherence to a wall) carries the jet into the innominate artery. Experimental observations utilizing an aortic arch model demonstrated that kinetic energy developed in a jet stream under conditions simulating supravalvular aortic stenosis is sufficient to account for the clinically observed differences in arterial pressure. Selective narrowing of the origins of the left carotid and left subclavian arteries (see Fig 7.7 B) is an uncommon cause of asymmetric pulses. In normal adults, the systolic pressure in the right arm is 10 to 15 mm Hg higher than in the left arm. Simultaneous determination of blood pressure in both arms minimizes these differences, and the technique of palpation shown in Fig. 7.13 is useful in the clinical comparison of the right and left brachial pulses. ^,

In valvular and fixed subaortic aortic stenosis, arterial thrills or shudders are common in the suprasternal notch and over the carotid and subclavian arteries. ^{, ,} In supravalvular aortic stenosis, the thrill is distinctly more pronounced over the right carotid artery which exhibits increased pulsation.

Precordial movement and palpation

Neonates with severe aortic valve stenosis have a prominent right ventricular impulse because of pulmonary hypertension and a left-to-right shunt at an atrial level. With these exceptions, the characteristic precordial impulse is left ventricular, varying from normal in mild aortic stenosis to the strong sustained impulse generated by an hypertrophied left ventricle of severe aortic stenosis. ^, Presystolic distention is in response to the increased force of left atrial contraction ( Fig. 7.14 ), which is evidence that the aortic stenosis is hemodynamically appreciable. Dilatation of the ascending aorta rarely transmits an impulse because the rate of ejection is blunted by the stenotic aortic valve. If an ascending aortic impulse occurs at all, it is likely to do so in patients with mild obstruction and an aortic aneurysm (see Fig. 7.4 ).

Systolic thrills are trivial or absent when aortic stenosis is mild or when severe aortic stenosis occurs with left ventricular failure. The thrill radiates upward and to the right, is maximal in the second right intercostal space, and is detected in the suprasternal notch and over both carotid arteries. The thrill in infants is sometimes maximum to the left of the sternum, inviting a mistaken diagnosis of ventricular septal defect. Even in older children, the thrill is occasionally more pronounced in the second or third left interspace, although radiation is still upward and to the right. In supravalvular aortic stenosis, the thrill is especially prominent below the right clavicle and on the right side of the neck.