page 686"; name_="Valvular and Vascular Conditions: Zipes: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine"; Zipes: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., fengqz and hbhstdx @ dxy 2005
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Valvular and Vascular Conditions

Left Ventricular Outflow Tract Lesions ( Fig. 56-30 )
COARCTATION OF THE AORTA

Aortic arch obstruction may be divided into (1) localized coarctation in close proximity to a PDA or ligamentum, (2) tubular hypoplasia of some part of the aortic arch system, and (3) aortic arch interruption.

Localized Aortic Coarctation
MORPHOLOGY.

This lesion consists of a localized shelf in the posterolateral aortic wall opposite the ductus arteriosus. A neonatal presentation is more often associated with a shelf plus transverse aortic arch and isthmic hypoplasia, whereas with a later presentation these areas are larger.[211] [212]

CLINICAL FEATURES.

Coarctation occurs two to five times more commonly in males, and there is a high degree of association with gonadal dysgenesis (Turner syndrome) and bicuspid aortic valve. Other common associated anomalies include VSD and mitral stenosis or regurgitation. Additional lesions have an impact on outcome.[213]

NEONATES.

Rapid, severe obstruction in infancy is a prominent cause of left ventricular failure and systemic hypoperfusion. Heart failure in this setting is due to a sudden increase in left ventricular wall stress after closure of the arterial duct. Substantial left-to-right shunting across a patent foramen ovale and pulmonary venous hypertension secondary to heart failure cause pulmonary arterial hypertension. Because little or no aortic obstruction existed during fetal life, the collateral circulation in the newborn period is often poorly developed. In these infants, peripheral pulses characteristically are weak throughout the body until left ventricular function is improved with medical management; a significant pressure difference then develops between the arms and the legs, allowing detection of a pulse discrepancy.


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Cardiac murmurs are nonspecific in infancy and commonly are derived from associated lesions.

ECG.

This shows right axis deviation and right ventricular hypertrophy.

Chest Radiography.

This shows generalized cardiomegaly and pulmonary arterial and venous engorgement.

Echocardiography ( Fig. 56-31A ).

This demonstrates the posterior shelf and the degree of associated isthmic and/or transverse arch hypoplasia. Doppler echocardiography is helpful if the ductus is closed or partially restrictive and demonstrates a high-velocity jet during systole and diastole. On the other hand, if the ductus is widely patent, then the usual right-to-left shunting makes the Doppler assessment invalid, because the distal pressure then reflects the high pulmonary artery pressure. With associated tubular hypoplasia, Doppler-derived gradients provide higher and less reliable values compared with those obtained by blood pressure or catheterization measurements.[214] [215]

MRA.

Although this is the gold standard for evaluation of the aortic arch in the older child and adult, it is usually unnecessary in the neonate and infant. [216]

Management usually involves prostaglandin therapy in an attempt to reopen or maintain patency of a ductus arteriosus. After prostaglandin E1 infusion to dilate the ductus arteriosus, the pressure difference may be obliterated across the site of coarctation because the fetal flow pattern is reestablished. This has the additional benefit of improving renal perfusion, which in turn helps reverse the frequently associated metabolic acidosis.

Intervention in this age group usually involves surgical relief of the obstruction with excision of the area of coarctation and extended end-to-end repair or end-to-side anastomosis with absorbable sutures to allow remodeling of the aorta with time.[217] Subclavian flap aortoplasty, which was employed extensively in the past, is now less popular than the earlier-mentioned procedures. It is generally believed that balloon dilation does not play a role in management in this age group. Early surgery is associated with a lower incidence of long-term hypertension.[217]


Figure 56-30 Montage demonstrating the different types of left ventricular outflow tract obstruction (asterisks). The upper left image shows isolated fibromuscular obstruction, the upper right stenosis due to a bicuspid aortic valve, the lower left due to chordal apparatus from the anterior mitral leaflet, and the lower right due to tunnel narrowing at the valve, annular, and subvalve level. AO = aorta; LA = left atrium; LV = left ventricle.

INFANTS AND CHILDREN
Presentation.

Most infants and children with isolated coarctation are asymptomatic, with the findings of reduced femoral pulses and/or hypertension being detected during routine medical care of the pediatric patient. Heart failure is uncommon because the left ventricle has a chance to become hypertrophied, thus maintaining a normal wall stress. Complaints of headache, cold extremities, and claudication with exercise may be noted in the older child and adolescent.

A midsystolic murmur over the anterior chest, back, and spinous processes is most frequent, becoming continuous if the lumen is sufficiently narrowed to result in a high-velocity jet across the lesion throughout the cardiac cycle. Additional systolic and continuous murmurs over the lateral thoracic wall may reflect increased flow through dilated and tortuous collateral vessels, which are commonly not heard until later childhood.


Figure 56-31 A, Montage of a coarctation of the aorta. The left image is a specimen that shows the site of the posterior shelf, as outlined by the arrow. The right image is from an MRI and shows the posterior shelf and some associated transverse arch hypoplasia. B, Angiogram of a coarctation of the aorta, before and after stenting. AO = aorta; DA = descending aorta.


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ECG.

This reveals left ventricular hypertrophy of various degrees, depending on the height of arterial pressure above the obstruction and the patient's age. Coexisting right ventricular hypertrophy usually implies a complicated lesion.

Chest Radiography.

The characteristic posteroanterior film feature is the so-called figure-3 configuration of the proximal descending thoracic aorta due to both prestenotic and poststenotic dilation. Rib notching (unilateral or bilateral, second to ninth ribs) is present in 50 percent of cases. Rib notching is unilateral if the right or left subclavian arteries arise from the aorta distal to the coarctation. Rib notching is noted as an erosion of the undersurface of a posterior rib, usually at its outer third, with a sclerotic margin.

Echocardiography.

This demonstrates a posterior shelf, a well-expanded isthmus and transverse aortic arch (in most cases), and a high-velocity continuous jet through the coarctation site. Of interest there is a slow upstroke on the abdominal aortic velocity profile when compared to that seen in the ascending aorta.

MRI.

This provides detailed information in this age group and may be performed prior to intervention, particularly if balloon dilation is the treatment of choice. This is the best tool for post-intervention imaging and has become routine in many centers.[216]

Angiocardiography.

This is reserved for delineating the coarctation at the time of balloon dilation.

Primary management in those cases with a well-expanded isthmus and transverse aortic arch invariably involves balloon dilation.[218] Surgery is usually reserved for cases where there is associated arch hypoplasia that requires a patch, as well as coarctation resection.

Paradoxical hypertension of short duration is often noted in the immediate postoperative period, a phenomenon much less common after balloon angioplasty. A resetting of carotid baroreceptors and increased catecholamine secretion appears to be responsible for the initial phase of postoperative systemic hypertension, with a later, second phase of prolonged elevation of systolic and particularly diastolic blood pressure related to activation of the renin-angiotensin system. A necrotizing panarteritis of the small vessels of the gastrointestinal tract of uncertain cause occasionally complicates the course of recovery.

Recoarctation.

The risk of recurrent narrowing after repair of coarctation in infancy is 5 to 10 percent. Such narrowing is best screened for with Doppler ultrasonography, with MRI being the gold standard for imaging. Clinical decisions to intervene are usually based on a cuff blood pressure difference between the right arm and leg (for a left aortic arch and normal innominate artery). Although there are no hard and fast rules for absolute blood pressure difference, it has been common practice to reintervene when the blood pressure difference is more than 25 to 30 mm Hg, in the presence of systemic hypertension. Although Doppler measurements can detect the presence of a recurrent obstruction, this technique provides an overestimation of the blood pressure-measured gradients due to the phenomenon of pressure recovery. [214] Recoarctation is usually addressed with balloon dilation if the obstruction is relatively localized. In the presence of long-segment narrowings, surgical intervention may be necessary, with the use of patch augmentation of the hypoplastic segment. More recently in the adolescent or adult, balloon-expandable stents have been employed with good success.[219] This has the advantage of avoiding the risk of potential neurological damage in post-intervention cases that invariably have poorly developed collaterals.

Long-Term Complications.

In those patients who survive the first 2 years of life, complications of juxtaductal coarctation are uncommon before the second or third decade.[220] [221] [222] The chief hazards to patients with coarctation result from severe hypertension and include the development of cerebral aneurysms and hemorrhage, hypertensive encephalopathy, rupture of the aorta, left ventricular failure, and infective endocarditis. Systemic hypertension in the absence of residual coarctation has been observed in resting or exercise-stressed patients postoperatively and appears to be related to the duration of preoperative hypertension.[11] [223] Life-long observation is desirable because of the late onset of hypertension in some postoperative patients.

ADULTS.

Although much of the previous material is also relevant in the adult, there are some differences in the issues faced by adult patients. Complex coarctation is used to describe coarctation in the presence of other important intracardiac anomalies (e.g., VSD, left ventricular outflow tract obstruction, and mitral stenosis) and is usually detected in infancy. Simple coarctation refers to coarctation in the absence of such lesions. It is the most common form detected de novo in adults. Associated abnormalities include bicuspid aortic valve in most cases; intracranial aneurysms (most commonly of the circle of Willis) in up to 10 percent; and acquired intercostal artery aneurysms. One definition of significant coarctation requires a gradient greater than 20 mm Hg across the coarctation site at angiography with or without proximal systemic hypertension. A second definition of significant coarctation requires the presence of proximal hypertension in the company of echocardiographic or angiographic evidence of aortic coarctation. If there is an extensive collateral circulation, there may be minimal or no pressure gradient and acquired aortic atresia.

Death in patients who do not undergo repair is usually due to heart failure (usually > 30 years of age), coronary artery disease, aortic rupture/dissection, concomitant aortic valve disease, infective endarteritis/endocarditis, or cerebral hemorrhage.[224] [225] Of Turner syndrome patients, 35 percent have aortic coarctation.

Clinical Features.

Patients can be asymptomatic, or they can present with minimal symptoms of epistaxis, headache, and leg weakness on exertion or more serious symptoms of congestive heart failure, angina, aortic stenosis, aortic dissection, or unexplained intracerebral hemorrhage. Leg claudication (pain) is rare unless there is concomitant abdominal aortic coarctation (Somerville J, personal communication, 1998). A thorough clinical examination reveals upper limb systemic hypertension as well as a differential systolic blood pressure of at least 10 mm Hg (brachial > popliteal artery pressure). Radial-femoral pulse delay is evident unless significant aortic regurgitation coexists. Auscultation may reveal an interscapular systolic murmur emanating from the coarctation site and a widespread crescendo-decrescendo systolic murmur throughout the chest wall from intercostal collateral arteries. Fundoscopic examination can reveal "corkscrew" tortuosity of retinal arterioles.

INTERVENTIONAL OUTCOMES
Surgical.

After surgical repair of simple coarctation, the obstruction is usually relieved with minimal mortality (1 percent). Paraplegia due to spinal cord ischemia is uncommon (0.4 percent) and may occur in patients who do not have well-developed collateral circulation. The prevalence of recoarctation reported in the literature varies widely, from 7 to 60 percent depending on the definition used, the length of follow-up, and the age at surgery. The appropriateness of the surgical repair for a given anatomy is probably the main factor dictating the chance of recoarctation rather than the type of surgical repair itself.[226] True aneurysm formation at the site of coarctation repair is also a well-recognized entity, with a reported incidence between 2 and 27 percent.[227] [228] [229] Aneurysms are particularly common after Dacron patch aortoplasty and usually occur in the native aorta opposite the patch. Late dissection at the repair site is rare, but false aneurysms, usually at the suture line, can occur. Long-term follow-up after surgical correction of coarctation of the aorta


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still reveals an increased incidence of premature cardiovascular disease and death. [230] [231]

Transcatheter.

After balloon dilation ( Fig. 56-31B ), aortic dissection, restenosis, and aneurysm formation at the site of coarctation all have been documented.[232] [233] [234] [235] [236] These complications may well be reduced if stents are used.[219] The significance of aneurysm formation is often unknown, and longer-term data are needed.[237]

Prior hypertension resolves in up to 50 percent of patients but may recur later in life, especially if the intervention is performed at an older age.[230] [231] In some of these patients this may be essential hypertension, but a hemodynamic basis should be sought and blood pressure control should be attained. Systolic hypertension is also common with exercise and is not a surrogate marker for recoarctation of the aorta.[11] It may be related to residual arch hypoplasia or to increased renin and catecholamine activity from residual functional abnormalities of the precoarctation vessels. The criteria for and significance of exertional systolic hypertension are controversial.[11] Late cerebrovascular events occur, notably in those patients undergoing repair as adults and in those with residual hypertension. Endocarditis or endarteritis can occur at the coarctation site or on intracardiac lesions; and if this occurs at the coarctation site, embolic manifestations are restricted to the legs.

FOLLOW-UP.

All patients should have follow-up examination every 1 to 3 years. Particular attention should be directed toward residual hypertension; heart failure; intracardiac disease, such as an associated bicuspid aortic valve, which can become stenotic or regurgitant later in life; or an ascending aortopathy sometimes seen in the presence of bicuspid aortic valve. Complications at the site of repair such as restenosis and aneurysm formation should also be sought using clinical examination, chest radiography, echocardiography, and periodic MRI or CT scanning. Patients with Dacron patch repair should probably undergo an MRI[238] or spiral CT examination every 3 to 5 years or so to detect subclinical aneurysm formation. Hemoptysis from a leaking or ruptured aneurysm is a serious complication requiring immediate investigation and surgery. New or unusual headaches raise the possibility of berry aneurysms. Endocarditis prophylaxis is recommended for any residual turbulent flow.

AORTIC ARCH HYPOPLASIA
MORPHOLOGY.

The aortic isthmus, the portion of the aorta between the left subclavian artery and the ductus arteriosus, should be narrowed in the fetus and newborn. The lumen of the aortic isthmus is about two-thirds that of the ascending and descending portions of the aorta until age 6 to 9 months, when the physiological narrowing disappears. Pathological tubular hypoplasia of the aortic arch usually is noted in the aortic isthmus and is most commonly associated with presentation of aortic coarctation in the newborn period. Despite this, there is a small group of cases where the arch obstruction is due primarily to tubular hypoplasia, usually involving both the aortic isthmus and transverse aortic arch (between the innominate and subclavian artery). These cases usually present early on in life with similar findings to those with a severe coarctation of the aorta. As with the latter, they are duct dependent and may also be associated with other left-sided obstructive lesions.

MANAGEMENT OPTIONS.

Provided the other left-sided structures are formed well enough to sustain life, the management involves arch reconstruction with a patch, in a similar fashion to those cases undergoing a Norwood procedure for hypoplastic left heart syndrome. If the left-sided structures are hypoplastic, then palliative surgery with a Norwood procedure or cardiac transplantation are the two treatments of choice.

Complex Coarctation.

In some instances the coarctation of the aorta is part of a more complex spectrum of lesions. This can be seen in cases with double-outlet right ventricle, cc-TGA, D-TGA, functionally single ventricle, truncus arteriosus, and AV septal defect. In these cases the decision process involves not only the coarctation repair but the management of the associated lesion(s). In the current era, the general trend is to complete repair of the intracardiac lesion at the same time as the arch repair.

SINUS OF VALSALVA ANEURYSM AND FISTULA
MORPHOLOGY.

The malformation consists of a separation, or lack of fusion, between the media of the aorta and the annulus fibrosus of the aortic valve. The receiving chamber of a right aortic sinus aortocardiac fistula is usually the right ventricle, but occasionally, when the noncoronary cusp is involved, the fistula drains into the right atrium. Five to 15 percent of aneurysms originate in the posterior or noncoronary sinus. The left aortic sinus is seldom involved. Associated anomalies are common and include a VSD, bicuspid aortic valve, and aortic coarctation.

CLINICAL FEATURES.

The deficiency in the aortic media appears to be congenital. Reports in infants are exceedingly rare and are infrequent in children, because progressive aneurysmal dilation of the weakened area develops but may not be recognized until the third or fourth decade of life, when rupture into a cardiac chamber occurs.[239] [240] [241] A congenital aneurysm of an aortic sinus of Valsalva, particularly the right coronary sinus, is an uncommon anomaly that occurs three times more often in males. An unruptured aneurysm usually does not produce a hemodynamic abnormality. Rarely, myocardial ischemia may be caused by coronary arterial compression. Rupture is often of abrupt onset, causes chest pain, and creates continuous arteriovenous shunting and acute volume loading of both right and left heart chambers, which promptly results in heart failure. An additional complication is infective endocarditis, which may originate either on the edges of the aneurysm or on those areas in the right side of the heart that are traumatized by the jetlike stream of blood flowing through the fistula.

The presence of this anomaly should be suspected in a patient with a combination of chest pain of sudden onset, resting or exertional dyspnea, bounding pulses, and a loud, superficial, continuous murmur accentuated in diastole when the fistula opens into the right ventricle, as well as a thrill along the right or left lower sternal border. The physical findings can be difficult to distinguish from those produced by a coronary arteriovenous fistula.

LABORATORY INVESTIGATIONS
ECG.

This may show biventricular hypertrophy, or it may be normal.

Chest Radiography.

This may demonstrate generalized cardiomegaly and usually heart failure.

Echocardiography.

Studies based on 2D and pulsed Doppler echocardiography may detect the walls of the aneurysm and disturbed flow within the aneurysm or at the site of perforation, respectively. TEE may provide more precise information than the transthoracic approach.[242] [243]

Cardiac Catheterization.

This reveals a left-to-right shunt at the ventricular or, less commonly, the atrial level; the diagnosis may be established definitively by retrograde thoracic aortography.

MANAGEMENT OPTIONS AND OUTCOMES.

Preoperative medical management consists of measures to relieve cardiac failure and to treat coexistent arrhythmias or endocarditis, if present. At operation, the aneurysm is closed and amputated, and the aortic wall is reunited with the heart, either by direct suture or with a prosthesis. Every effort should be made to preserve the aortic valve in children because patch closure of the defect combined with prosthetic


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valve replacement greatly enhances the risk of operation in small patients. Rarely, device closure of the ruptured aneurysm has been attempted.[244]

VASCULAR RINGS
MORPHOLOGY.

The term vascular ring is used for those aortic arch or pulmonary artery malformations that exhibit an abnormal relation with the esophagus and trachea, often causing dysphagia and/or respiratory symptoms.[245]

DOUBLE AORTIC ARCH ( Fig. 56-32 ).

The most common vascular ring is produced by a double aortic arch in which both the right and left fourth embryonic aortic arches persist. In the most common type of double aortic arch, there is a left ligamentum arteriosum or occasionally a ductus arteriosus. Although both arches may be patent at the time of diagnosis, invariably the left arch distal to the left subclavian artery is atretic and is connected to the descending aorta by a fibrous remnant that completes the ring. In the setting where both arches are patent, the right arch is usually larger than the left. This usually occurs as an isolated lesion, with the respiratory symptoms being caused by tracheal compression and frequently associated laryngomalacia, usually in the neonate and young infant.

RIGHT AORTIC ARCH.

A right aortic arch with a left ductus or ligamentum arteriosum connecting the left pulmonary artery and the upper part of the descending aorta is the next most important vascular ring seen. Although all with this lesion have a vascular ring, not all cases are symptomatic. Indeed those patients who are symptomatic usually have an associated diverticulum of Kommerrell.[246] This is a large out-pouching at the distal takeoff of the left subclavian artery from the descending aorta. It is the combination of the diverticulum and the ring that causes the airway compression.

ANOMALOUS ORIGIN OF A RIGHT SUBCLAVIAN ARTERY.

This is one of the most common abnormalities of the aortic arch that is encountered. Although the aberrant right subclavian artery runs posterior to the esophagus it does not form a vascular ring unless there is an associated right-sided ductus or ligamentum to complete the ring. During adulthood about 5 percent of patients with an aberrant right subclavian artery (and a left ductus) develop symptoms due to rigidity of the aberrant vessel.

RETROESOPHAGEAL DESCENDING AORTA.

This is a rarer but more problematic type of vascular ring. In this setting there may be either an ascending left and descending right, or an ascending right and descending left, aorta. The retroesophageal component of the descending aorta causes


Figure 56-32 The left image is a three-dimensional reconstruction of a double aortic arch from an MRI, whereas the right image is from an aberrant left subclavian artery as seen by spiral CT. LSA = left subclavian artery; TR = trachea.

the tracheal compression, in conjunction with the left- or right-sided ligamentum. [247] [248]

PULMONARY ARTERY SLING.

This is usually made up of the left pulmonary artery arising from the right pulmonary artery and runs posterior to the trachea but anterior to the esophagus. This is usually seen in isolation and is associated with significant hypoplasia of the bronchial tree, which is the predominant cause of the airway symptoms.

CLINICAL FEATURES.

The symptoms produced by vascular rings depend on the tightness of anatomical constriction of the trachea and esophagus and consist principally of respiratory difficulties including stridor, cyanosis (especially with feeding), and dysphagia. Not all patients with a vascular ring are symptomatic, and cases with an aberrant left subclavian artery are frequently detected at the time of evaluation for associated CHD. Although most patients with a true ring and some airway compression present early on in life, others present later on with dysphagia, with others escaping diagnosis forever.

LABORATORY INVESTIGATIONS
ECG.

This appears normal unless associated cardiovascular anomalies are present.

Chest Radiography.

If there is evidence of a right aortic arch in a symptomatic patient, then a vascular ring should be suspected. In some instances there is evidence of some airway narrowing. The barium esophagogram is a useful screening procedure. Prominent posterior indentation of the esophagus is observed in many of the common vascular ring arrangements, although the pulmonary artery vascular sling produces an anterior indentation.

Echocardiography.

This is a very sensitive tool for evaluating the laterality of the aortic arch, including a detailed assessment of the associated brachiocephalic vessels.[249] In general if there is normal branching of the innominate artery, to the right for a left aortic arch and to the left for a right, along with the correct "sidedness" of the descending aorta, then a vascular ring can be excluded. Most cases with a double aortic arch have a dominant right arch, with the descending aorta appearing to dip posteriorly as it runs behind the esophagus. A patent ductus or ligamentum can usually be identified by echocardiography. When both arches are patent, a frontal plane sweep from inferior to superior demonstrates both patent arches, as well as their brachiocephalic vessels. A right aortic arch with an aberrant left subclavian artery is suspected when it is not possible to identify normal branching of the left-sided innominate artery. A retroesophageal descending aorta should be suspected when the ascending aorta and its brachiocephalic arteries are readily identified but there is difficulty in identifying the descending aorta as it traverses behind the esophagus. A left pulmonary artery sling is suspected when the normal branching pattern of pulmonary arteries cannot be identified. In this setting color Doppler permits the identification of the left pulmonary artery as it arises from the right pulmonary artery and runs in a posterior and leftward direction.

MRI and CT.

MRI and CT play a major role in the evaluation of patients with a vascular ring. In fact MRA has become the gold standard for the evaluation of the aorta and its branches. The only disadvantage for infants is that it often requires general anesthesia to achieve a successful examination. On the other hand, spiral CT is a technique that is fast and provides better definition of the affected airways. This latter technique is particularly valuable for patients with a pulmonary artery sling, where the vascular ring plays a secondary role to the airway abnormalities. The advantages of these techniques are that, unlike echocardiography,


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they permit a precise assessment of the more posterior vascular structures and their relationships to the esophagus and airways. These techniques are particularly valuable in the more complex forms, such as a retroesophageal descending aorta.

Management Options and Outcomes.

The severity of symptoms and the anatomy of the malformation are the most important factors in determining treatment. Patients, particularly infants, with respiratory obstruction require prompt surgical intervention.[250] A left thoracotomy is the surgical approach in most patients with a vascular ring. For the most common vascular rings such as a double aortic arch or aberrant left subclavian artery, the combination of a chest radiograph, barium swallow, and echocardiogram is all that is necessary prior to surgical intervention.

Operative repair of the double aortic arch requires division of the minor arch (usually the left) and the ligamentum. Patients with a right aortic arch and a left ductus or ligamentum arteriosum require division of the ductus or ligamentum and/or ligation and division of the left subclavian artery, which is the posterior component of the ring. Video-assisted thoracoscopy holds promise as an alternative to open thoracotomy for management.[251] [252] In patients with a pulmonary artery vascular sling, operation consists of detachment of the left pulmonary artery at its origin and anastomosis to the main pulmonary artery directly or by way of a conduit with its proximal end brought anterior to the trachea.

CONGENITAL AORTIC VALVE STENOSIS
GENERAL CONSIDERATIONS.

We deal here only with this condition in newborns and children, since the adult presentation is dealt with in Chapter 52 . Congenital aortic valve stenosis is a relatively common anomaly. Congenital aortic valve stenosis occurs much more frequently in males, with a gender ratio of 4:1. Associated cardiovascular anomalies have been noted in as many as 20 percent of patients. PDA and coarctation of the aorta occur most frequently with aortic valve stenosis; all three of these lesions may coexist.

MORPHOLOGY.

The basic malformation consists of thickening of valve tissue with various degrees of commissural fusion. The valve most commonly is bicuspid. In some patients, the stenotic aortic valve is unicuspid and dome shaped, with no or one lateral attachment to the aorta at the level of the orifice. In infants and young children with severe aortic stenosis, the aortic valve annulus may be relatively underdeveloped. This lesion forms a continuum with the hypoplastic left heart syndrome and the aortic atresia and hypoplasia complexes. Secondary calcification of the valve is rare in childhood. When the obstruction is hemodynamically significant, concentric hypertrophy of the left ventricular wall and dilation of the ascending aorta occur.

NEONATAL PRESENTATION.

The newborn presentation is often similar to that seen with other obstructive left-sided lesions, such as coarctation of the aorta or interrupted aortic arch. They present with heart failure and are dependent on ductal patency for survival. There is a frequent association with varying degrees of left ventricular hypoplasia, mitral valve abnormalities, and endocardial fibroelastosis. With the advent of good prenatal screening, many are detected before birth, with deliveries being performed in a high-risk obstetrical unit attached to a congenital heart facility. The decision process around single versus biventricular repair is a complex one and beyond the scope of this chapter. Suffice it to say there are formulas that have been derived to assist the pediatric cardiologist in the decision process.[253]

Clinical Findings.

The newborns generally have weak pulses throughout, signs of heart failure, and often little in the way of murmurs, despite the severe left ventricular outflow tract obstruction.

ECG.

This usually shows right ventricular dominance with evidence of diffuse ST wave changes due to left ventricular strain.

Chest Radiography.

This usually shows cardiomegaly due to a large right ventricle and varying degrees of pulmonary edema.

Echocardiography.

This is currently the diagnostic test of choice. It usually shows a poorly contracting left ventricle with varying degrees of endocardial fibroelastosis and frequently hypoplasia of the left ventricle and aortic root. Doppler assessment of gradients are often unreliable due to poor left ventricular function. The presence of right ventricular hypertension and tricuspid valve regurgitation are common associated findings.

Management.

Prostaglandin therapy is instituted in this patient population to maintain the fetal circulation with retrograde ductal flow that permits coronary and cerebral perfusion. The nature of further treatment depends on whether the left ventricle and aortic root are believed to be of a sufficient size to support a biventricular repair. If so, balloon dilation is rapidly becoming the treatment of choice,[254] though surgical intervention is still preferred by some.[255] If the left heart structures are believed to be too small to sustain life, then either cardiac transplantation or a Norwood procedure can be undertaken.[253]

PRESENTATION BEYOND THE NEWBORN PERIOD.

The diagnosis is invariably made following the detection of a murmur. Occasionally heart failure ensues, usually in the first 1 to 2 months of life when there is a rapid progression of the obstruction and lack of left ventricular mass to maintain a normal wall stress. The natural history studies performed several years ago demonstrated that more rapid progression of aortic valve stenosis is more likely to happen within the first 2 years of life, following which the rate of progressive obstruction is more uniform.[256] [257]

Clinical Findings.

In general the children are asymptomatic, having normal peripheral pulses if the stenosis is less severe and low-volume, slow-rising pulses when it progresses. Exercise fatigue and chest pain are rare complaints and occur only when the stenosis is severe. With severe stenosis there is systolic thrill in the same area that can also be felt in the suprasternal notch and carotid arteries. Beyond the newborn period there is usually an ejection click at the apex that precedes the murmur. The second heart sound is usually normal in children. There is an ejection systolic murmur heard along the left sternal border, with radiation into the right infraclavicular area. Associated aortic regurgitation may be heard.

ECG.

Left ventricular hypertrophy with or without strain are the hallmark features.

Chest Radiography.

Overall heart size is normal, or the degree of enlargement is slight in most children with congenital aortic valve stenosis.

Echocardiography.

2D echocardiography provides detailed information about the morphology of the valve, the left ventricular function, and the presence of associated left-sided lesions. Doppler echocardiography can be used to determine the severity of stenosis and the presence or absence of associated aortic regurgitation. Doppler provides peak instantaneous gradients that are higher than the peak-to-peak gradients determined from cardiac catheterization.[258] [259] The importance of this lies in the fact that the natural history studies and clinical decision-making have thus far been based on peak-to-peak catheterization gradients in the infant, child, and adolescent. Valve areas are usually not calculated in this age group because there are no good data to support their use in pediatric patients. Mean gradients as derived from Doppler and catheterization correlate closely, but again there is lack of data to support their use in clinical decision-making. Some data exist that convert the Doppler-derived mean gradients to


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peak to peak, with the addition of the pulse pressure as obtained from blood pressure measurements. Whatever absolute number is chosen to work with, the additional finding of left ventricular hypertrophy on ECG and echocardiography provide supportive data regarding timing for intervention. There is general agreement in the pediatric population that a peak-to-peak gradient of 60 mm Hg or more probably warrants intervention.

Diagnostic Cardiac Catheterization.

Cardiac catheterization is now rarely used to establish the site and severity of obstruction to left ventricular outflow. Instead, catheterization is undertaken when therapeutic interventional balloon aortic valvuloplasty is indicated.

Management Options.

In this current era balloon dilation has almost completely replaced primary surgical valvotomy in children.

FOLLOW-UP.

Follow-up studies indicate that aortic valvotomy is a safe and effective means of palliative treatment with excellent relief of symptoms. Aortic insufficiency can occasionally be progressive and require valve replacement.[260] [261] [262] Moreover, after commissurotomy, the valve leaflets remain somewhat deformed, and it is likely that further degenerative changes, including calcification, will lead to significant stenosis in later years. Thus, prosthetic aortic valve replacement is required in approximately 35 percent of patients within 15 to 20 years of the original operation. For those children and adolescents requiring aortic valve replacement, the surgical options include replacement with a mechanical aortic valve, an aortic homograft, or a pulmonary autograft in the aortic position. Accumulating evidence shows that the pulmonary autograft may ultimately be preferable to the aortic homograft. In the pulmonary autograft, called the Ross procedure, the patient's pulmonary valve is removed and used to replace the diseased aortic valve, and the right ventricular outflow tract is reconstructed with a pulmonary valve homograft.[262] [263] We consider it likely that the Ross procedure will emerge as the approach of choice in the future,[263] although caution is needed when applied to patients with bicuspid aortic valve and aortic regurgitation.[264] This surgical approach can be applied from neonatal through to adult life. Neither homografts nor autografts require anticoagulation.

SUBAORTIC STENOSIS
MORPHOLOGY
Discrete Fibromuscular.

This lesion consists of a ridge or fibrous ring encircling the left ventricular outflow tract at varying distances from the aortic valve.[265] The subvalvular fibrous process usually extends onto the aortic valve cusps and almost always makes contact with the ventricular aspect of the anterior mitral leaflet at its base. In other cases with fibrous discontinuity between the mitral and aortic valves, it forms more of a tunnel obstruction.

Focal Muscular.

Rarely there is no fibrous element, but rather a focal muscular obstruction on the crest of the interventricular septum, which differs from cases with hypertrophic cardiomyopathy.

Hypoplasia of the Left Ventricular Outflow Tract.

In some cases, valvular and subvalvular aortic stenoses coexist with hypoplasia of the aortic valve annulus and thickened valve leaflets, producing a tunnel-like narrowing of the left ventricular outflow tract. Additional findings often include a small ascending aorta.

Discrete Subaortic Stenosis and VSD.

This combination is frequently encountered in the pediatric age group, with the fibromuscular component often being absent at the initial echocardiographic evaluation. The association should be suspected in those VSDs with some associated anterior malalignment of the aorta and a more acute aortoseptal angle.[266] These hearts frequently develop subpulmonary stenosis. In a different subset of patients with aortic arch interruption and a VSD, there is muscular subaortic stenosis due to posterior deviation of the infundibular septum.

Complex Subaortic Stenosis.

Various anatomical lesions other than a discrete ridge may produce subaortic stenosis. Among these are abnormal adherence of the anterior leaflet of the mitral valve to the septum and the presence in the left ventricular outflow tract of accessory endocardial cushion tissue.[267] [268] These are frequently associated with a "cleft in the anterior mitral valve leaflet," which is to be differentiated from that seen in an AV septal defect. These types of obstruction are seen more commonly in those cases with abnormalities of the ventriculoarterial connection in association with a VSD (e.g., double-outlet right ventricle, transposition, and VSD).

CLINICAL FEATURES.

These types of obstruction are usually identified as secondary lesions in those cases with associated VSDs, with or without abnormalities of the ventriculoarterial connections or aortic arch obstruction. In general the substrate for left ventricular outflow tract obstruction is present, though in some cases actual physiological obstruction is absent. In other cases the patients are referred with a systolic murmur for evaluation. In the those cases with a gradient across their left ventricular outflow tract, there is an ejection systolic murmur heard along the lower left sternal border with the absence of an ejection click.

LABORATORY INVESTIGATIONS
ECG.

In those with associated defects the ECG reflects the major abnormality rather than the associated left ventricular outflow tract obstruction. With isolated forms of left ventricular outflow tract obstruction, there may be left ventricular hypertrophy when the obstruction is significant.

Chest Radiography.

This is usually unhelpful in these cases.

Echocardiography.

Echocardiography is the current standard diagnostic tool in this lesion.[269] Not only can it permit an accurate delineation of the mechanisms of obstruction but it provides detailed data regarding associated lesions. In all forms the parasternal long-axis view is key to providing an accurate diagnosis. The presence of mitral aortic discontinuity, the relationship of a fibromuscular ridge to the aortic valve, the presence of accessory obstructive tissue, and the dimensions of the aortic annulus and root all are well imaged in this view. As well, color-flow mapping permits the identification of associated aortic valve regurgitation and provides hemodynamic evidence of the site of onset of obstruction. The extension of a fibromuscular ridge onto the anterior mitral leaflet is best appreciated in the apical five-chamber view. As well, this provides the best site for pulsed or continuous-wave Doppler assessment of the maximum gradient across the left ventricular outflow tract. In the older patient TEE plays an important role in delineating the pathology.[270]

Cardiac Catheterization.

This technique is no longer of importance in evaluating this lesion. Although balloon dilation has been attempted, it is generally believed that this is a surgical lesion.

MRI.

In general, MRI is unnecessary unless there are problems obtaining the needed information by echocardiography.

INTERVENTIONAL OPTIONS.

Surgical intervention is indicated either at the time of the repair of the underlying primary lesion or in those cases with discrete obstruction when the obstruction is severe enough to raise concerns.

Discrete Subaortic Stenosis (Fibrous and Muscular).

The rate of progression is varied and may be slow.[271] In general the approach to the latter group has been to intervene when there is a mean gradient across the left ventricular outflow tract of greater than 30 mm Hg to avoid future aortic leaflet damage.[272] Surgery involves a fibromectomy, with care to avoid damage to the aortic valve or to create a traumatic VSD.[273] There is a recurrence rate of subaortic stenosis requiring


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reoperation in up to 20 percent of cases. In some the recurrence is in the form of a fibrous ridge, whereas in others there is acquired pathology of the aortic valve in the form of stenosis as well as regurgitation. Reoperation may involve just repeat resection of a recurrent fibrous ridge, or it may involve surgery for the aortic valve in those cases with significant aortic regurgitation.

Complex Forms of Left Ventricular Outflow Tract Obstruction and an Intact Ventricular Septum.

In cases with an intact ventricular septum the indications for intervention are similar to those cases with discrete obstruction. The difference lies in the fact that the surgical approach has to be modified according to the underlying pathology. Resection of any fibromuscular component or accessory tissue (provided it is not a primary support mechanism for the mitral valve), a valve-sparing Konno operation, and, in those cases with a hypoplastic aortic annulus, a classic Konno procedure with aortic valve replacement, are the potential surgical options.[274] [275]

Left Ventricular Outflow Tract Obstruction and Complex Forms of CHD.

In general, surgery to the left ventricular outflow tract is part of the general repair of the lesion and is not dependent on the precise degree of obstruction across this site.

OUTCOMES.

Immediate complications related to surgery include complete AV block, creation of a VSD, or mitral regurgitation from intraoperative damage to the mitral valve apparatus. Long-term complications include recurrence of fibromuscular subvalvular left ventricular outflow tract obstruction (up to 20 percent). Clinically important aortic regurgitation is not uncommon (up to 25 percent of patients). In some cases with predominant acquired aortic valve stenosis, balloon dilation has been the treatment of choice.

FOLLOW-UP.

Particular attention should be paid to patients with residual or recurrent subaortic stenosis or those with an associated bicuspid aortic valve or important aortic regurgitation because they are most likely to require surgery eventually. Patients with bioprosthetic aortic valves in the aortic position (following the Konno procedure) or the pulmonary position (following the Ross-Konno procedure) need close follow-up. Endocarditis prophylaxis should be used for prosthetic valves or in the presence of any residual lesions.

SUPRAVALVULAR AORTIC STENOSIS
MORPHOLOGY.

Three anatomical types of supravalvular aortic stenosis are recognized, although some patients may have findings of more than one type. Most common is the hourglass type, in which marked thickening and disorganization of the aortic media produce a constricting annular ridge at the superior margin of the sinuses of Valsalva. The membranous type is the result of a fibrous or fibromuscular semicircular diaphragm with a small central opening stretched across the lumen of the aorta. Diffuse hypoplasia of the ascending aorta characterizes the third type.

Because the coronary arteries arise proximal to the site of outflow obstruction in supravalvular aortic stenosis, they are subjected to the elevated pressure that exists within the left ventricle. These vessels often are dilated and tortuous, and premature coronary arteriosclerosis has been described. Moreover, if the free edges of some or all of the aortic cusps adhere to the site of supravalvular stenosis, coronary artery inflow may be compromised. The left ventricle may have a "ballerina foot" configuration, which can result in muscular left ventricular outflow tract obstruction, particularly when associated with significant supravalvular obstruction.

CLINICAL FEATURES.

The clinical picture of supravalvular obstruction differs in major respects from that observed in the other forms of aortic stenosis. Chief among these differences is the association of supravalvular aortic stenosis with idiopathic infantile hypercalcemia, a disease that occurs in the first years of life and can be associated with deranged vitamin D metabolism.

WILLIAMS SYNDROME.

The designation supravalvular aortic stenosis syndrome, Williams syndrome, or Williams-Beuren syndrome has been applied to the distinctive picture produced by coexistence of the cardiac and a multisystem disorder.[276] Beyond infancy in these patients, a challenge with vitamin D- or calcium-loading tests unmasks abnormalities in the regulation of circulating 25-hydroxyvitamin D. Infants with Williams syndrome often exhibit feeding difficulties, failure to thrive, and gastrointestinal problems in the form of vomiting, constipation, and colic. The entire spectrum of clinical manifestations includes auditory hyperacusis, inguinal hernia, a hoarse voice, and a typical personality that is outgoing and engaging. Other manifestations of this syndrome include intellectual impairment, "elfin facies", narrowing of peripheral systemic and pulmonary arteries, strabismus, and abnormalities of dental development consisting of microdontia, enamel hypoplasia, and malocclusion.

Many medical conditions can complicate the course of Williams syndrome, including systemic hypertension, gastrointestinal problems, and urinary tract abnormalities. In an older child or adult, progressive joint limitation and hypertonia may become a problem. Adult patients are usually handicapped by their developmental disabilities.

Williams syndrome was previously considered to be nonfamilial; however, a number of families in which parent-to-child transmission of Williams syndrome has occurred have now been identified. All of these families show a parent and child to be affected with Williams syndrome, including one instance of male-to-male transmission. This supports autosomal dominant inheritance as the likely pattern, with most cases of Williams syndrome probably occurring as the result of a new mutation. New information indicates that a genetic defect for supravalvular aortic stenosis is located in the same chromosomal subunit as elastin on chromosome 7q11.23.[277] Elastin is an important component of the arterial wall, but precisely how mutations in elastin genes cause the phenotypes of supravalvular aortic stenosis is not known.

FAMILIAL AUTOSOMAL DOMINANT PRESENTATION.

Occasionally the aortic anomaly and peripheral pulmonary arterial stenosis are also found in familial and sporadic forms not associated with the other features of the syndrome.[278] Affected patients have normal intelligence and are normal in facial appearance. Genetic studies suggest that when the anomaly is familial, it is transmitted as autosomal dominant with variable expression. Some family members may have peripheral pulmonary stenosis either as an isolated lesion or in combination with the supravalvular aortic anomaly.

CLINICAL FEATURES.

Patients with Williams syndrome are intellectually challenged ( Fig. 56-33 ). The typical appearance is similar to that of the elfin facies observed in the severe form of idiopathic infantile hypercalcemia and is characterized by a high prominent forehead, stellate or lacy iris patterns, epicanthal folds, underdeveloped bridge of the nose and mandible, overhanging upper lip, strabismus, and anomalies of dentition. Recognition of this distinctive appearance, even in infancy, should alert the physician to the possibility of underlying multisystem disease. In addition, a positive family history in a patient with a normal appearance and clinical signs suggesting left ventricular outflow obstruction should lead to the suspicion of either supravalvular aortic stenosis or hypertrophic obstructive cardiomyopathy.

Studies of the natural history of the principal vascular lesions in these patients—supravalvular aortic stenosis and peripheral pulmonary artery stenosis[279] —indicate that the aortic lesion is usually progressive, with an increase in the


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Figure 56-33 Typical elfin facies in three patients with supravalvular aortic stenosis. (From Friedman WF, Kirkpatrick SE: Congenital aortic stenosis. In Adams FH, Emmanouilides GC, Riemenschneider TA, et al [eds]: Moss' Heart Disease in Infants, Children, and Adolescents. 4th ed. Baltimore, Williams & Wilkins, 1989.)

intensity of obstruction related often to poor growth of the ascending aorta. In contrast, the patients with pulmonary branch stenosis, whether associated with the aortic lesion or not, tend to show no change or a reduction in right ventricular pressure with time.[280] [281]

With few exceptions, the major physical findings resemble those observed in patients with aortic valve stenosis. Among these exceptions are accentuation of aortic valve closure due to elevated pressure in the aorta proximal to the stenosis, an absent ejection click, and the especially prominent transmission of a thrill and murmur into the jugular notch and along the carotid vessels. The narrowing of the peripheral pulmonary arteries may produce a late systolic or continuous murmur heard best in the lung fields and usually are accentuated by inspiration. Another hallmark of supravalvular aortic stenosis is that the systolic pressure in the right arm is usually higher than in the left arm. This pulse disparity may relate to the tendency of a jet stream to adhere to a vessel wall (Coanda effect) and selective streaming of blood into the innominate artery.

LABORATORY INVESTIGATIONS
ECG.

This usually reveals left ventricular hypertrophy when obstruction is severe. Biventricular or even right ventricular hypertrophy may be found if there is significant narrowing of peripheral pulmonary arteries.

Chest Radiography.

In contrast to valvular and discrete subvalvular aortic stenosis, poststenotic dilation of the ascending aorta is absent.

Echocardiography.

This is a valuable technique for localizing the site of obstruction to the supravalvular area.[282] Most often the sinuses of Valsalva are dilated, and the ascending aorta and arch appear small or of normal size. The diameter of the aortic annulus is always greater than that of the sinotubular junction. Doppler examination determines the location of obstruction but usually overestimates the gradient compared with that obtained at cardiac catheterization. This results from the obstruction being lengthy, and the Doppler gradient is overestimated due to the phenomena of pressure recovery.

Angiocardiography.

In most cases, this is necessary to define an accurate hemodynamic gradient across the left ventricular outflow tract, as well as to determine the status of the coronary arteries. Usually it also involves an assessment of the branch pulmonary arteries as well as the brachiocephalic, renal, and mesenteric arteries, all of which can be stenotic. Because of the nature of the anatomical defect, transcatheter balloon angioplasty, with or without stenting, is not an effective treatment option.

INTERVENTIONAL OPTIONS AND OUTCOMES.

Surgical intervention for the supravalvular aortic stenosis has been successful in most cases with good medium and long-term results.[283] [284] A variety of surgical procedures may be performed, all of which are tailored to the type of pathology. The use of a Y patch, resection with end-to-end anastomosis, or a Ross procedure are the main techniques employed. Additional lesions, including coronary ostial stenosis, aortic valvuloplasty, and subaortic resection, may be necessary in some cases.

The cardiac prognosis is very good, with some patients requiring further surgery for recurrent supravalvular stenosis.[279] [285] As peripheral pulmonary artery stenosis tends to improve with time, there is a reluctance to attempt intervention, either surgical or via balloon angioplasty. Long-term behavioral and intellectual problems persist. [285]

Congenital Mitral Valve Anomalies
CONGENITAL MITRAL STENOSIS
MORPHOLOGY.

Anatomical types of mitral stenosis include the parachute deformity of the valve, in which shortened chordae tendineae converge and insert into a single large papillary muscle; thickened leaflets with shortening and fusion of the chordae tendineae; an anomalous arcade of obstructing papillary muscles; accessory mitral valve tissue; and a supravalvar circumferential ridge or "ring" of connective tissue arising at the base of the atrial aspect of the mitral leaflets.[286] Associated cardiac defects are common, including endocardial fibroelastosis, coarctation of the aorta, PDA, and left ventricular outflow tract obstruction. There is also an association between persistence of the left superior vena cava and obstructive left-sided lesions.[287]

CLINICAL FEATURES.

In most cases the findings are incidental at the time of evaluation of another left-sided obstructive lesion, such as coarctation of the aorta or aortic valve stenosis. The classic auscultatory findings seen with rheumatic mitral valve stenosis are often absent in the congenital form. Typical findings include a normal S1 , a mid-diastolic murmur with or without some presystolic accentuation, and no opening snap.


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LABORATORY INVESTIGATIONS
ECG.

In milder forms this is usually normal, or there may be left atrial overload, with or without right ventricular hypertrophy due to associated pulmonary hypertension.

Chest Radiography.

This is normal in milder forms, with evidence of pulmonary edema in those cases with more severe obstruction.

Echocardiography.

The 2D echocardiography, combined with Doppler studies, usually provides a complete analysis of the anatomy and function of congenital mitral stenosis. [288] The status of the papillary muscles is best appreciated in the precordial short-axis view. In patients with two papillary muscles, they are usually closer together than is seen in the normal heart. The precordial long-axis view permits identification of a supravalvular mitral ring as well as the degree of mobility of the valve leaflets. Color flow Doppler allows identification of the level of the obstruction, as well as the presence of mitral valve regurgitation. Pulsed or continuous-wave Doppler provides an accurate assessment of the mean gradient across the mitral valve. The advantage of the pressure half-time lies in the fact that it is independent of cardiac output, unlike the mean gradient across the mitral valve. Due to more rapid heart rates in children, the pressure half-time is of less value.

INTERVENTIONAL OPTIONS AND OUTCOMES.

In asymptomatic cases clinical and echocardiographic follow-up is all that is necessary. If the patient starts to develop pulmonary hypertension or symptoms, surgical intervention is usually indicated. Mitral valve balloon dilation [289] is not as successful as it is in rheumatic mitral valve stenosis. Surgery usually involves removing a supramitral ring if present, splitting papillary muscles and fused chordal apparatus in those cases with more common forms of congenital mitral stenosis. In general, surgical intervention provides temporary relief, with many operated cases requiring valve replacement later in life. [290] [291]

CONGENITAL MITRAL REGURGITATION
MORPHOLOGY
Isolated Congenital Mitral Valve Regurgitation.

This is usually due to either an isolated cleft of the anterior mitral valve leaflet[292] or as the result of leaflet dysplasia. In these cases there is evidence of shortened chordae in conjunction with dysplastic valve leaflets. In those with an isolated mitral valve cleft, the deficiency in the anterior mitral leaflet points toward the left ventricular outflow tract, unlike those cases with an AV septal defect. In general, the larger the cleft in the anterior mitral leaflet, the greater the degree of regurgitation.

In cases with a dysplastic mitral valve the chordal apparatus is shortened with varying degrees of dysplasia of the leaflets. Other anatomical lesions such as mitral valve arcade resulting in regurgitation are usually part of a more generalized abnormality of the left side of the heart.

Complex Congenital Mitral Valve Regurgitation.

This is seen more frequently in association with abnormalities of the ventriculoarterial connection, such as double-outlet right ventricle, transposition and VSD, and corrected transposition. In the first two it is frequent to have a cleft in the anterior mitral valve leaflet with some chordal support apparatus that renders the valve less regurgitant than in those cases with an isolated cleft. In cc-TGA the morphological mitral valve may have an associated cleft, be dysplastic, or have multiple papillary muscles, all of which increase the tendency for it to be regurgitant.

CLINICAL FEATURES.

The presence of symptoms relates to the severity of the regurgitation in those cases where the pathology is isolated to the valve. Exercise intolerance, combined with a pansystolic murmur at the apex, with or without a mid-diastolic murmur, are the cardinal clinical features.

LABORATORY INVESTIGATIONS
ECG.

This is either normal or demonstrates left atrial and left ventricular hypertrophy.

Chest Radiography.

This demonstrates cardiomegaly predominantly involving the left ventricle and atrium.

Echocardiography.

Doppler and 2D echocardiography provide an accurate evaluation of the mechanisms and degree of valvular regurgitation.[288] [292] The cleft in the anterior mitral valve leaflet is best seen in the precordial short-axis view, pointing toward the left ventricular outflow tract. Patients with a dysplastic mitral valve lack mobility of the valve leaflets and have shortened chordae. Color Doppler interrogation helps in locating the site of regurgitation. The severity of regurgitation is assessed in the standard fashion. The 3D echocardiography permits a comprehensive evaluation of the mechanisms of regurgitation, with additional information being obtained regarding commissural length, leaflet area, and sites of regurgitation from color flow Doppler.

Angiocardiography and MRI.

These procedures are seldom helpful in management planning.

INTERVENTIONAL OPTIONS AND OUTCOMES.

This depends on the severity of regurgitation and its impact on left ventricular function. Surgery should not be delayed until the patients become symptomatic. Surgery involves suture of an isolated cleft, with or without associated commissuroplasties. In those cases with a dysplastic mitral valve, leaflet extension in conjunction with an annuloplasty and commissuroplasty usually results in effective control of the regurgitation in the short and medium term.[293] Despite this, many of these patients most likely end up with a mitral valve replacement at some stage in the future. Attempted surgical repair, rather than replacement, is important in the pediatric age group, because it permits temporary relief that allows the child to grow such that future surgery can be done into a larger mitral annulus. When required, mitral valve replacement has had a good short- and medium-term outcome in those cases where repair is not possible.[294]

Right Ventricular Outflow Tract Lesions
PERIPHERAL PULMONARY ARTERY STENOSIS ( Fig. 56-34 )

Right ventricular outflow tract is a term that applies to those patients with both peripheral pulmonary artery stenosis and an intact ventricular septum. It excludes those with an associated VSD, which is dealt with in the sections on tetralogy


Figure 56-34 Right ventricular angiocardiogram showing numerous sites of peripheral pulmonic stenosis and poststenotic dilation of the peripheral pulmonic arteries.


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of Fallot and pulmonary atresia with a ventricular septal defect. Also excluded is Noonan syndrome, which is dealt with in the subsequent section on pulmonary valve stenosis.

ETIOLOGY
Rubella Syndrome.

The most important cause of significant pulmonary artery stenoses producing symptoms in newborns used to be intrauterine rubella infection. Other cardiovascular malformations commonly found in association with congenital rubella include PDA, pulmonary valve stenosis, and ASD. Generalized systemic arterial stenotic lesions also may be a feature of the rubella embryopathy, which may involve large and medium-sized vessels such as the aorta and coronary, cerebral, mesenteric, and renal arteries. Cardiovascular lesions are but one manifestation of intrauterine rubella infection because cataracts, microphthalmia, deafness, thrombocytopenia, hepatitis, and blood dyscrasias are also common. The clinical picture in infants with rubella syndrome depends on the severity of the cardiovascular lesions and the associated abnormalities.

Williams Syndrome.

Peripheral pulmonary artery stenosis is also associated with supravalvular aortic stenosis in patients with Williams syndrome, which is discussed in the section on supravalvular aortic stenosis.[295]

Alagille Syndrome.

Peripheral pulmonary artery stenosis is a component of this syndrome, with some cases having a JAG1 mutation.[296]

Isolated Branch Pulmonary Artery Stenosis.

This is encountered mainly in the proximal left pulmonary artery and is invariably related to a sling of ductal tissue that causes stenosis when the ductus arteriosus closes after birth. In most cases this is fairly mild, but a significant obstruction resulting in failure of distal growth of the left pulmonary artery may also be seen.

MORPHOLOGY.

Apart from the isolated form mentioned earlier, the stenoses are usually diffuse and bilateral and extend into the mediastinal, hilar, and intraparenchymal pulmonary arteries.

CLINICAL FEATURES.

The degree of obstruction is the principal determinant of clinical severity. The type of obstruction determines the feasibility of intervention. Most patients are asymptomatic. An ejection systolic murmur heard at the upper left sternal border and well transmitted to the axillae and back is most common. There is no pulmonary ejection click. The pulmonic component of the second heart sound may be accentuated and is loud only if there is proximal pulmonary hypertension. A continuous murmur is often audible in patients with significant branch stenosis. The murmurs in the lung fields are typically increased by inspiration.

LABORATORY INVESTIGATIONS
ECG.

Right ventricular hypertrophy is seen when obstruction is severe. Left axis deviation with counterclockwise orientation of the frontal QRS vector is common in rubella syndrome and when there is also supravalvular aortic stenosis.

Chest Radiography.

Mild or moderate stenosis usually produces normal findings. Detectable differences in vascularity between regions of the lungs or dilated pulmonary artery segments are uncommon. When obstruction is bilateral and severe, right atrial and ventricular enlargement may be seen.

Echocardiography.

Echocardiography is helpful in making the diagnosis and excluding associated lesions; however, it is limited in its ability to image the distal pulmonary arteries beyond the hilum of the lung. Right ventricular pressure assessment may be predicted if there is associated tricuspid valve regurgitation.

MRI and Spiral CT.

These are valuable diagnostic tests because they permit a more distal evaluation of the branch pulmonary arteries. The advantage of spiral CT in young children is that it can be performed without the need for heavy sedation or even general anesthesia. Although most patients require cardiac catheterization and angiography, these other techniques are excellent for the initial evaluation and for following the progress of the lesions.

Radionuclide Quantitative Lung Perfusion Scan.

This is valuable in those cases with unilateral stenosis to determine whether intervention is necessary. Similar flow estimates can now be obtained by MRI.

Cardiac Catheterization and Angiocardiography.

This permits the assessment of right ventricular pressure and the pressures in the pulmonary arterial tree. Angiocardiography is the key to precisely assessing the extent and severity of the stenoses.

INTERVENTIONAL OPTIONS AND OUTCOMES.

For those cases with isolated left pulmonary artery stenosis where there is less than 30 percent of flow to the lung, balloon dilation with or without stent insertion is effective in relieving the obstruction. In those cases with more diffuse bilateral stenoses, the indications for intervention depend on the right ventricular pressure. As the natural history of diffuse peripheral pulmonary artery stenosis in Williams syndrome is one of potential regression over time, intervention is in general reserved for those cases with systemic or suprasystemic right ventricular pressure. Intervention is also dependent in part on the extent of the stenosis and the dilation capability of the lesions, with or without stenting.[297] [298] [299] In some cases, several attempts at dilation are required to achieve any improvement in vessel caliber. High-pressure balloons are usually needed, but some lesions cannot be dilated even with such balloons. Recently, improved results have been reported using "cutting" balloons, which may facilitate dilation in an otherwise undilatable stenosis. As a rule, surgery has little to offer those patients with diffuse peripheral pulmonary artery stenoses and can indeed make the situation worse.

SUPRAVALVULAR RIGHT VENTRICULAR OUTFLOW TRACT OBSTRUCTION

Supravalvular right ventricular outflow tract obstruction seldom occurs in isolation. It can occur in tetralogy of Fallot, Williams syndrome, Noonan syndrome, VSD, or arteriohepatic dysplasia (Alagille syndrome). Supravalvular right ventricular outflow tract obstruction can progress in severity and should be monitored. Dilation of the pulmonary trunk is not a feature of subvalvular and supravalvular right ventricular outflow tract obstruction. Intervention is recommended when the peak gradient across the right ventricular outflow tract is more than 50 mm Hg at rest or when the patient is symptomatic.

PULMONARY STENOSIS WITH INTACT VENTRICULAR SEPTUM ( Fig. 56-35 and Fig. 56-36 )

This lesion exists as a continuum, ranging from those patients with isolated valvular stenosis to others where there is complete atresia of the pulmonary outflow tract. There are two modes of presentation. The first presents in the neonatal period, usually with associated pathology of the tricuspid valve, right ventricle, and/or coronary arteries. The second mode of presentation is beyond the neonatal period, when the valvular stenosis is usually isolated. Some cases with severe stenosis diagnosed in utero can present with valvular atresia at the time of birth.

MORPHOLOGY.

The pulmonary valve may vary from a well-formed trileaflet valve with varying degrees of commissural fusion to an imperforate membrane. If stenosis is present, the right ventricle is usually of normal size or only mildly hypoplastic. Those patients with an imperforate valve and a patent infundibulum invariably have a larger right ventricular volume than cases with both infundibular and valve atresia.


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CLINICAL FEATURES
Neonate with Critical Pulmonary Valve Stenosis.

The neonate presents with central cyanosis due to right-to-left shunting at the atrial level and depends on a prostaglandin infusion to maintain the patency of the ductus arteriosus. Auscultatory findings include a single second heart sound, no ejection click, and a murmur that, when present, is due to tricuspid valve regurgitation.

Infant and Child.

In cases beyond the newborn period the referral is usually for the assessment of a cardiac murmur. This may be detected within the first few weeks of life, more commonly at the routine 6-week postnatal visit or later. These patients usually have an ejection click and a second heart sound that moves with respiration but with a soft pulmonary component. There is an ejection murmur of varying intensity and duration heard best in the pulmonary area.

Adult.

Adults with isolated mild to moderate right ventricular outflow tract obstruction of any type are usually asymptomatic. Patients with severe right ventricular outflow tract obstruction may present with exertional fatigue, dyspnea, lightheadedness, and chest discomfort (right ventricular angina). Physical examination may reveal a prominent jugular A wave, a right ventricular lift, and possibly a thrill in the 2nd left interspace. Auscultation reveals a normal S1 , a single or split S2 with a diminished P2 (unless the obstruction is supravalvular in which case the intensity of the P2 is normal or increased), and a systolic ejection murmur best heard in the 2nd left intercostal space. When the pulmonary valve is thin and pliable, a systolic ejection click will be heard which decreases on inspiration. As the severity of the pulmonary stenosis progresses, the interval between S1 and the systolic ejection click becomes shorter, S2 becomes widely split, P2 diminishes or disappears, and the systolic ejection murmur lengthens and peaks later in systole, often extending beyond A2 . An ejection click seldoms occur with dysplastic pulmonary stenosis. Cyanosis may be present when a patent foramen ovale or ASD permits right-to-left shunting.

Adult patients with trivial and mild valvular right ventricular outflow tract obstruction do not become worse with time. Moderate valvular right ventricular outflow tract obstruction can progress in 20 percent of unoperated patients, [300] especially in adults because of calcification of the valve, and may require intervention. Some of these patients can also become symptomatic, particularly in later life, because of atrial arrhythmias resulting from right ventricular pressure overload and tricuspid regurgitation. Patients with severe valvular right ventricular outflow tract obstruction will have had balloon or surgical valvotomy to survive to adult life. Long-term survival in patients with repaired pulmonary valve stenosis is similar to that of the general population, with excellent to good functional class at long-term follow-up


Figure 56-35 Montage of pulmonary valve stenosis demonstrating typical pathology (left, arrow) with a thickened pulmonary valve and obstruction due to commissural fusion. Note the post-stenotic dilation. The angiogram demonstrates a case before (middle, arrow) and during (right) balloon dilation. MPA = main pulmonary artery; RV = right ventricle.


Figure 56-36 Right ventriculogram (RV) in the lateral projection (left) from a patient with valvular pulmonic stenosis. The pulmonary valve (PV) is thickened and domes in systole (arrows). Poststenotic dilation of the pulmonary artery (PA) is seen. At the right, successful balloon valvuloplasty shows almost complete disappearance of the stenotic waist (arrow). (Courtesy of Dr. Thomas G. DiSessa.)

in most patients. A few patients have severe pulmonary regurgitation.

LABORATORY INVESTIGATIONS
ECG.

In the newborn period this may show left axis deviation and left ventricular dominance in those cases with significant right ventricular hypoplasia. Other patients may have a normal QRS axis. Right atrial overload is present in those with increased right atrial pressure. In the infant, child, and adult the findings are dependent on the severity of the stenosis. In milder cases the ECG should be normal. As the stenosis progresses, evidence of right ventricular hypertrophy appears. Severe stenosis is seen in the form of a tall R wave in lead V4 R or V1 with a deep S wave in V6 . A tall QR wave in the right precordial leads with T wave inversion and ST segment depression (right ventricular "strain") reflects very severe stenosis. When an rSR' pattern is observed in lead V1 (20 percent of patients), lower right ventricular pressures are found than in patients with a pure R wave of equal amplitude. Right atrial overload is associated with moderate to severe pulmonary stenosis.

Chest Radiography.

In the neonate this demonstrates pulmonary oligemia with a prominent right heart border in those with associated tricuspid valve regurgitation. In the infant, child, and adult with mild or moderate pulmonary stenosis, chest radiography often shows a heart of normal size and


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normal pulmonary vascularity. Poststenotic dilation of the main and left pulmonary arteries is often seen. Right atrial and right ventricular enlargement are observed in patients with severe obstruction and right ventricular failure. The pulmonary vascularity is usually normal in the absence of a right-to-left atrial shunt but may be reduced in patients with severe stenosis and right ventricular failure.

Echocardiography.

Combined 2D echocardiographic and continuous-wave Doppler examination characterizes the anatomical valve abnormality and its severity and has essentially eliminated the requirement for diagnostic cardiac catheterization. Invasive studies are currently used for balloon valvuloplasty.

Right ventricular size is currently best assessed indirectly from the tricuspid annular dimension. In the absence of a VSD there is an excellent correlation between the two. Right ventricular pressure can be assessed indirectly from the tricuspid regurgitation gradient. Tricuspid valve morphology and function and the status of the interatrial septum all need to be addressed.

INTERVENTIONAL OPTIONS AND OUTCOMES
Neonate.

In the neonate, prostaglandin E1 is instituted in those cases with ductal dependency. Following this, balloon dilation is performed in those with stenosis, whereas radiofrequency perforation in conjunction with dilation may be undertaken in those with pulmonary valve atresia. If relief of the obstruction is successful, then the prostaglandins are slowly weaned to determine if the right ventricle is large enough to support the circulation. If not, a systemic-to-pulmonary artery shunt is necessary early in the management. In those cases with a normal-sized right ventricle, no further therapy is usually necessary in the future, since there is a very low recurrence rate of stenosis. Newborns with isolated pulmonary stenosis do well after relief of the stenosis.

Infant and Older Child.

Balloon dilation of the pulmonary valve is the therapeutic procedure of choice with excellent short- and medium-term results.

Adults.

Balloon valvuloplasty is recommended when the gradient across the right ventricular outflow tract is greater than 50 mm Hg at rest[206] or when the patient is symptomatic. Intermediate- and long-term outcomes are excellent. [301]

DYSPLASTIC PULMONARY VALVE STENOSIS
MORPHOLOGY.

In pulmonary valve stenosis due to valvular dysplasia the obstruction is caused not by commissural fusion but by a combination of thickened and dysplastic pulmonary valve leaflets in combination with varying degrees of supravalvular pulmonary stenosis. The supravalvular stenosis is classically at the distal part of pulmonary valve sinuses, and there is usually no poststenotic pulmonary artery dilation. This entity is associated with Noonan syndrome, which in turn may be associated with hypertrophic cardiomyopathy.

CLINICAL FEATURES.

In most cases, the diagnosis is made either during an evaluation of a systolic murmur or in a child with dysmorphic features who is undergoing clinical evaluation. Children with Noonan syndrome have short stature, webbed necks, and broad-shaped chests in a fashion similar to Turner syndrome. Although this syndrome does not have an associated chromosomal abnormality, it may be familial and affects both sexes equally. A unique association in the newborn is pulmonary lymphangiectasia. The auscultatory finding that differentiates the dysplastic valves from simple pulmonary valve stenosis is the lack of an ejection click. The other features of the murmur are similar to that described in pulmonary valve stenosis.

ECG.

The ECG is helpful in that patients with dysplastic pulmonary stenosis frequently have a leftward QRS axis, particularly when associated with hypertrophic cardiomyopathy. The remainder of the ECG is similar to that seen in pulmonary valve stenosis.

Chest Radiography.

The findings are similar to typical pulmonary valve stenosis, apart from the lack of post-stenotic pulmonary trunk dilation, even in the presence of severe obstruction. In those with pulmonary lymphangiectasia the chest radiograph has a ground-glass appearance, which can be difficult to differentiate from pulmonary venous obstruction.

Echocardiography.

This demonstrates a thickened fleshy pulmonary valve, lack of post-stenotic dilation, and varying degrees of supravalvular pulmonary stenosis. The associated diagnosis of hypertrophic cardiomyopathy can be confirmed or excluded. If the initial echocardiogram does not demonstrate hypertrophic cardiomyopathy, then further studies should be performed throughout childhood and adolescence, particularly in those cases with left axis deviation.

INTERVENTIONAL OPTIONS AND OUTCOMES
Cardiac Catheterization and Angiography.

Although the results of balloon valvuloplasty are less rewarding than those with stenosis due to commissural fusion, it is worth attempting this before considering surgical intervention. There has been varied success, with many cases having some reduction in gradient that can delay surgery.

Surgical Intervention.

If balloon valvuloplasty fails, then surgical intervention is indicated. This usually involves a partial valvectomy in conjunction with patch repair of the supravalvular stenosis.

Outcomes.

Adequate relief of the right ventricular outflow tract obstruction results in an excellent outlook, with the greatest long-term risk factor being the presence of hypertrophic cardiomyopathy.

SUBPULMONARY RIGHT VENTRICULAR OUTFLOW TRACT OBSTRUCTION (ANOMALOUS MUSCLE BUNDLES OR A DOUBLE-CHAMBERED RIGHT VENTRICLE)
MORPHOLOGY.

A double-chambered right ventricle is formed by right ventricular obstruction due to anomalous muscle bundles.[302] [303] Although this can occur in isolation, it is more frequently part of a combination of lesions that includes right ventricular muscle bundles, a perimembranous-outlet VSD, and subaortic stenosis with or without aortic valve prolapse.

CLINICAL FEATURES.

Most cases are discovered as an incidental finding during the evaluation of a VSD.[304] In some cases there may be only an ejection systolic murmur. If the obstruction is isolated, then there is an ejection systolic murmur heard best in the upper left sternal border. If the VSD is the predominant lesion, the right ventricular outflow tract murmur may not be appreciated. Before the routine use of echocardiography, the diagnosis was often made during follow-up for a VSD when the pansystolic murmur decreased in intensity and a systolic ejection murmur emerged. The patients are usually pink unless there is progression of the subpulmonary stenosis in the setting of a VSD. The diagnosis may be more problematic in adults.[305] [306]

LABORATORY INVESTIGATIONS
ECG.

The ECG is similar to those with isolated pulmonary valve stenosis beyond the newborn period. In cases with a nonrestrictive VSD and mild subpulmonary stenosis, the ECG typically shows biventricular hypertrophy due to a left-to-right shunt and associated pulmonary hypertension. If the stenosis is more severe, right ventricular hypertrophy will be seen. Those with a restrictive VSD may have a normal ECG or left ventricular hypertrophy, the latter of which is replaced with right ventricular hypertrophy if the subpulmonary stenosis increases in severity.

Chest Radiography.

This is usually normal in those with isolated subpulmonary stenosis, whereas those with a VSD


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may have increased or reduced pulmonary blood flow, depending on the severity of the obstruction.

Echocardiography.

Doppler and 2D echocardiography usually provide a complete diagnosis. [304] The level of subpulmonary obstruction is appreciated best in a combination of subcostal right anterior oblique and precordial short-axis views. These views permit the identification of the relationship of the VSD to the muscle bundles, as well as the degree of anterior malalignment of the infundibular septum in those with a VSD. The precordial short-axis view is the best position to evaluate the presence of possible subaortic stenosis and aortic cusp prolapse. Color and pulsed or continuous-wave Doppler evaluation usually allows differentiation of the VSD flow jet from that originating from the muscle bundles. This permits an accurate assessment of the hemodynamic effect of the subpulmonary obstruction.

Cardiac Catheterization and Angiocardiography.

This technique is rarely necessary.[304] In older patients where the echocardiographic images of the subpulmonary region may be suboptimal, a combination of MRA[307] and echocardiography is all that is generally needed.

MANAGEMENT OPTIONS AND OUTCOMES.

Management is dictated by the severity of the subpulmonary stenosis and the presence of associated defects. In those patients with isolated subpulmonary stenosis, surgery is indicated when the right ventricular pressure is more than 60 percent of systemic. This involves resection of the muscle bundles through the right atrium. For those cases with an associated VSD, the decision is based on the size of the VSD, the degree of associated subaortic stenosis, the presence of aortic valve prolapse, and the severity of the subpulmonary stenosis. These patients tend to have a progressive disease, so many cases that are followed conservatively for several years will eventually require surgery.[306] In general, the outcome is excellent with a low rate of recurrence after surgical resection of obstructive muscle bundles.[308] Infrequently, recurrence of the subaortic obstruction may occur.

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