Chapter 484. Congenital Heart Disease

Congenital heart diseases occur in at least 10 per 1000 live-born children; the incidence is much higher in stillborn infants and in spontaneous abortuses. This figure excludes bicuspid aortic valves, patent ductus arteriosus in premature infants, and tiny muscular ventricular septal defects with respective incidences of 10 to 20, 4 to 5, and 30 to 40 per 1000 live-born children. The distributions of various common types of congenital heart diseases at birth are given in Table 484-1.

Etiology

Congenital heart diseases result from interaction between genetic and environmental factors.

Genetic Factors

Single classic mendelian mutant genes account for 3% of congenital heart diseases; 5% are caused by gross chromosomal aberrations, 3% by known environmental factors (eg, rubella, fetal alcohol syndrome), and the rest by multifactorial gene effects or single gene effects modulated by random events. The genetics of congenital heart disease are discussed in detail in Chapter 481.

Environmental Factors

Women taking lithium salts during pregnancy may have children with congenital heart diseases, with a high incidence of mitral and tricuspid valve lesions, especially Ebstein syndrome. Diabetic women or those taking progesterone in pregnancy have an increased risk of having children with congenital heart diseases. About half the children of alcoholic mothers have congenital heart diseases (usually left-to-right shunts). Retinoic acid used to treat acne may cause several types of congenital heart lesions.

Viral Lesions

Rubella embryopathy is often associated with peripheral pulmonic stenosis, patent ductus arteriosus, and valvar pulmonic stenosis. Other viruses, notably coxsackieviruses, have been thought to cause congenital heart diseases because of an increased frequency of rising serum titers to this virus in mothers whose infants have congenital heart disease. Mumps virus is responsible for endocardial fibroelastosis.

Counseling Families

The risk of occurrence of cardiac lesions in future children concerns parents. Chromosomal abnormalities have risks of recurrence that vary with the specific chromosomal change involved. Other forms of inheritance produce a much lower risk of recurrence (Table 484-1). Furthermore, if 2 first-degree relatives have congenital heart disease, then the risk of heart disease in the next infant is about 3 times as high as the figures just cited. The risk of transmission of congenital heart disease to children if the parent, especially the mother, has congenital heart disease averages about 5% to 10%. If another child has congenital heart disease, it is most often similar in type (concordant) to that in the parent or sibling.1-9

When a child is found to have congenital heart disease, the parents frequently have severe guilt feelings and are almost always worried about the risk of occurrence of congenital heart disease in future children. These issues should be discussed openly with the parents, who are often reticent about mentioning them. An explanation of what is known of the causes of congenital heart diseases and reassurance that the parents did not cause it by acts of omission or commission are arguments that can be used to help allay guilt feelings. This approach must be correlated with all other aspects of giving continued support to parents with chronically ill children.

A shunt from systemic to pulmonary circulation through an abnormal communication, termed a left-to-right shunt, lets oxygenated blood recirculate through the lungs without entering the peripheral arterial circulation. This shunt is wasted flow that adds to cardiac work without improving delivery of oxygenated blood. A left-to-right shunt may be present alone or associated with right-to-left shunting (bidirectional shunting) or obstructive lesions.

Left-to-right shunts are classified anatomically by the level at which the systemic and pulmonary circulations communicate.

With defects that produce left-to-right shunts after birth, fetal somatic development is unaltered, and blood flow to the fetal organs and placenta is probably normal. However, alterations of flow patterns in the fetal heart and great vessels may affect their development. When some left ventricular output is shunted away from the ascending aorta, as may occur in endocardial cushion defects, a large ventricular septal defect, or double-outlet right ventricle, particularly with aortic or subaortic obstruction, then decreased aortic isthmus flow may cause hypoplasia or even interruption of the aortic isthmus. Altered streaming patterns may change the composition of blood leaving the heart. Thus, with an endocardial cushion defect or large ventricular septal defect, the oxygen tension of blood leaving the right ventricle and perfusing the lungs may be higher than that in the normal fetus. This higher oxygen tension may alter the development of pulmonary resistance vessels, thereby affecting postnatal clinical features.

Defects associated with left-to-right shunts are shown in Table 483-4. Four major interrelated factors control the amount of left-to-right shunting postnatally: the size of and therefore the resistance to flow offered by the communication, the difference in pressures between the chambers or vessels, the relative distensibilities of the 2 ventricles, and the total outflow resistances (including peripheral resistances) of the chambers or vessels.

If the communication at any level is small, it offers a high resistance to flow through it so that the left-to-right shunt will be small, no matter what the pressures or resistances are. The latter 3 factors come into play only with medium-sized or big communications.

In pretricuspid (atrial level) communications, atrial pressures are low and almost equal, and the amount and direction of shunting depend only on the resistance to emptying of the left and right atria into their respective ventricles. Before and immediately after birth, systemic and pulmonary vascular resistances and pressures are high and equal, and both ventricles have similar wall thicknesses and distensibility. Therefore, diastolic inflow into each ventricle is similar, and even with a large atrial septal communication, there will be little left-to-right atrial shunting. Over the next few weeks, systemic pressures and vascular resistances increase while pulmonary vascular resistances and pressures decrease and the left ventricular wall becomes thicker and the right ventricular wall remains relatively thin, so that the diastolic distensibility becomes greater in the right than the left ventricle. Therefore, more blood flows from right atrium to right ventricle than from left atrium to left ventricle, so that a larger left-to-right shunt develops. (Think of the atria as a single chamber with 2 exits. More blood will enter the more distensible receiving chamber.) Note that the large left-to-right shunt can develop only after pulmonary arterial resistance and pressure have decreased greatly.

In a posttricuspid shunt such as a ventricular septal defect or patent ductus arteriosus, when the communication is large, systolic pressures in the ventricles or great arteries are equal, and the magnitude and direction of shunting will be determined by the relative outflow resistance of each ventricle or great artery. If left-sided outflow resistance is much higher than that of the right side, there will be a large left-to-right shunt. If right-sided outflow resistance increases and approximates that of the left side, or if systemic resistance falls, the left-to-right shunt will be small or even disappear. If the outflow resistance is higher for the right than the left side, there will be a shunt from right to left. The outflow resistance may be at a semilunar valve orifice, in a great vessel, in peripheral resistance vessels, or any combination of these. In the absence of aortic or pulmonic stenosis, the relationship between pulmonary and systemic vascular resistances determines the magnitude of shunting. Because systemic vascular resistance is normally high and changes relatively little after birth, alteration in pulmonary vascular resistance is the major regulator of shunting through a large aortopulmonary or interventricular defect, particularly in the first months after birth, when the normal progressive fall in pulmonary vascular resistance occurs. This type of shunting, in which the ratio of pulmonary vascular resistance to systemic vascular resistance determines the shunt, is termed dependent shunting, and it applies to both pre- and posttricuspid shunts (eTable 484.1).

Another group of left-to-right shunts has a communication between a high-pressure ventricle or artery and a low-pressure chamber or vein, such as a direct left ventricular to right atrial communication or a systemic arteriovenous fistula. The magnitude of the shunt depends on the size of the communication and the pressure difference between the chambers or vessels involved and not on the pulmonary vascular resistance; the shunt is therefore termed obligatory.

General Pathophysiology and Clinical Correlates

The site of the defect determines some of its specific features; however, many features associated with left-to-right shunting are common to several defects. A small left-to-right shunt has little hemodynamic effect on the heart and presents only with specific murmurs related to turbulent flow across the defect. Larger shunts, however, have prominent effects that depend on the level at which shunting occurs, because this determines which part of the circulation receives the additional blood flow. In general, the murmur indicates the site of the communication but not its severity. Severity is determined by signs of a hyperactive circulation, by clinical and roentgenographic examination, and in the most severe instances by congestive heart failure.

In an aortopulmonary left-to-right shunt, some of the left ventricular output leaves the systemic circulation and increases pulmonary blood flow by that amount. The resultant greater pulmonary venous return to the left atrium and left ventricle increases left ventricular diastolic volume and thus increases left ventricular stroke volume and stroke work by the Frank-Starling mechanism. The left ventricle is enlarged and hyperactive, with a forceful and hyperactive apical impulse. Because of the increased left ventricular output, there may be a third heart sound caused by rapid left ventricular filling in early diastole and a fourth heart sound from left atrial hypertrophy. Also, when pulmonary venous return to the left atrium approximately doubles, there may be a low-frequency apical mid-diastolic rumbling murmur from increased and turbulent diastolic flow across a normal mitral valve. Dilatation of the left ventricle elevates left ventricular end-diastolic and left atrial pressures and, if marked, causes left heart failure and pulmonary venous congestion. Left atrial dilatation may stretch the atrial septum, causing incompetence of the valve of the foramen ovale and a left-to-right atrial shunt that may be clinically significant. The right ventricle does not handle an extra volume load (unless there is an aorto-atrial shunt, as in a ruptured sinus of Valsalva aneurysm) but will have an increased pressure load if there is pulmonary hypertension. This produces a forceful heave felt at the lower left sternal border enlargement and a loud pulmonic valve closure sound (P2).

Similar hemodynamic effects may follow a left-to-right shunt at the ventricular level, but the right ventricle will also have some volume overload, so that the right ventricular impulse also is hyperactive. Left-to-right shunts at the atrial level increase volume load only on the right atrium and ventricle, and if there is some outflow obstruction, a moderately increased right ventricular systolic pressure load may also occur. Therefore, a hyperactive impulse is felt over the right but not the left ventricle. An increase in right ventricular end-diastolic pressure with a subsequent increase in right atrial and systemic venous pressures is not usual in childhood because of the great capacity of the right atrium and systemic venous system, but it may occur when right ventricular performance decreases. With obligatory shunts, volume overloading of both ventricles occurs, and both right and left ventricular impulses are hyperactive. Persistently increased precordial activity with cardiac enlargement in infants and young children often produces anterior bulging of the left hemithorax.

The sympathetic-adrenal system and myocardial hypertrophy help to maintain adequate myocardial performance, normal systemic output, and adequate tissue oxygenation in the face of a large left-to-right shunt. There is increased catecholamine release from the adrenal glands and sympathetic nerve fibers within the myocardium, so that heart rate and the force of myocardial contraction increase. This increased sympathetic-adrenal activity also accounts for the excessive sweating seen in left ventricular failure, particularly in infants. These compensatory mechanisms are well developed in older children and adults but not fully developed in newborn, particularly premature, infants. In addition, because myocardial structure matures during fetal and neonatal development, premature infants are less capable of handling a volume overload than are mature or older infants. If the increased volume or pressure load on the ventricles persists, the muscle fibers hypertrophy, and the increased amount of contractile protein helps to handle the load without excessive ventricular dilatation or sympathetic stimulation.

The increased workload and mass of the left ventricle increase myocardial oxygen requirements. Delivery of oxygen to the myocardium depends on coronary blood flow and the oxygen content of arterial blood. Coronary perfusion to the left ventricle, particularly the deep subendocardial muscle, occurs during diastole and depends on the systemic arterial–intramyocardial diastolic pressure difference as well as the duration of diastole. Therefore, a reduction in arterial diastolic pressure (as in an aortopulmonary communication with a large left-to-right shunt), an increase in left ventricular end-diastolic pressure and therefore subendocardial intramyocardial pressure (as with left ventricular failure), and a reduction in diastolic period (as with tachycardia) are all detrimental to myocardial perfusion and oxygen delivery. In the right ventricle, myocardial blood flow is unlikely to be compromised unless the right ventricle has a systemic systolic pressure and is hypertrophied.

A low hemoglobin content, as occurs with physiological anemia in early infancy or after repeated blood sampling during intensive nursery care, also jeopardizes oxygen delivery to the myocardium and may precipitate left ventricular failure. A shift of P50 to the left (alkalosis, some abnormal hemoglobins, fetal hemoglobin) also makes it more difficult to supply oxygen to the myocardium. In addition, anemia or a left shift of P50 places a further demand on the left ventricle to increase systemic output to supply adequate oxygen to the entire body. Similarly, infections may further stress the left ventricle by increasing tissue oxygen demands and thereby requirements for cardiac output.

Chest roentgenograms of posttricuspid shunts show left ventricular and left atrial enlargement, and in aortopulmonary communications, the ascending aorta, which carries the increased flow, may be dilated. Increased pulmonary blood flow is manifested by prominent dilated main and branch pulmonary arteries extending into the lung fields. If there is left ventricular failure, the roentgenogram shows the features described in Chapter 497. In pretricuspid shunts, the right ventricle and atrium are enlarged, and increased pulmonary blood flow is evident.

Electrocardiographic evidence of atrial and ventricular hypertrophy depends on the duration and magnitude of the shunt. Electrocardiographic features vary with the different types of atrial communication and are discussed later.

Echocardiographic findings also depend on the magnitude of left-to-right shunting and the degree of heart failure as well as on the specific lesion.

Effects on Pulmonary Circulation

With a large aortopulmonary or ventricular communication, systemic and pulmonary arterial pressures are similar, and because of the persistent high pulmonary arterial pressure, the medial muscle of the small pulmonary arteries does not regress as rapidly or as much as in normal individuals. Thus, although pulmonary vascular resistance falls rapidly immediately after birth because of the onset of ventilation, the subsequent decline in pulmonary vascular resistance is slower than normal. The lowest pulmonary vascular resistance reached is usually delayed 2 to 3 months and even then is higher than normal. Infants with large obligatory left-to-right shunts also have significantly increased pulmonary blood flow and therefore pulmonary arterial pressures that are higher than normal, because in early infancy the small pulmonary arteries are still thickened; this will also delay the medial smooth muscle regression. Regression of the medial muscular layer is also retarded by anything producing hypoxic pulmonary vasoconstriction in the newborn period, for example, high altitude, pulmonary disease, chronic upper airway obstruction, or obstruction of the major airways by dilated pulmonary arteries produced by a large left-to-right shunt. In patients with atrial communications, the pulmonary arterial pressure and pulmonary vascular resistance fall normally in the postnatal period, and small pulmonary arteries undergo the normal regression of medial smooth muscle.

Patent Ductus Arteriosus

Postnatal closure of the ductus arteriosus is effected by constriction of smooth muscle in its wall. In full-term infants, this functional closure normally occurs within 10 to 15 hours after birth; however, complete anatomic obliteration of the ductus arteriosus is slower and may not be complete until the third postnatal month. Because pulmonary vascular resistance falls as soon as the lungs expand, in the first 10 to 15 hours when the ductus arteriosus is still open, a left-to-right shunt through the ductus arteriosus may occur, and a murmur may be heard.

Causes of Persistent Patency

A clinically apparent patent ductus arteriosus occurs in 30% to 40% of premature infants with birth weights under 1750 g, and about 80% under 1000 g birth weight. The mechanisms responsible for continued patency are related to the inability of the ductus arteriosus in immature infants to respond normally to an increased oxygen tension and to changes in prostaglandin concentrations. (see Chapter 55). The incidence of persistent patency of the ductus arteriosus in full-term infants born at high altitude is significantly higher than in those born at sea level, probably because of the lower atmospheric oxygen tension. Persistent patency of the ductus arteriosus in full-term and occasional preterm infants at lower altitudes is generally related to a structural abnormality of the ductus arteriosus. No cause has been established in most patients, but a genetic basis has been inferred because this lesion fits the classic model of polygenic inheritance. Maternal rubella in the first trimester of pregnancy, however, is associated with a high incidence of persistent patency of the ductus arteriosus, and rubella virus has been cultured from ductus arteriosus tissue.

Clinical Manifestations in Mature Infants

The diagnosis of patent ductus arteriosus is easier in full-term infants or older children than in immature infants. Because of continuous runoff of blood from the aorta to the pulmonary artery through the ductus arteriosus, the murmur in older infants and children is continuous and has a rumbling, machinery-like or “train in a tunnel” quality, usually with late systolic accentuation of the murmur. It is heard best below the left clavicle. If the ductus arteriosus is small, this may be the only abnormal finding. If it is larger, the increase in left ventricular output is associated with an increase in stroke volume that causes a rapid rise in the aortic pulse pressure as a result of rapid left ventricular ejection and also causes left ventricular hyperactivity. The diastolic runoff through the aortopulmonary communication plus the peripheral vasodilatation from baroreceptor stimulation account for the low diastolic pressure and the collapsing pulse. The increased volume load enlarges the left atrium and ventricle, with roentgenographic evidence of dilatation and electrocardiographic evidence of hypertrophy. Because the ascending aorta receives the increased left ventricular output, it is dilated. On x-ray, the pulmonary vascular markings indicate increased pulmonary blood flow. If there is pulmonary hypertension, there may be signs of right ventricular pressure overload.

The echocardiogram shows the ductus arteriosus and may define its size, as well as assess the volume overload of the left ventricle.

Differential Diagnosis

In premature infants, particularly those under 1000 g birth weight, there is little chance that clinical findings suggestive of a patent ductus arteriosus are caused by some other congenital heart defect, because patency of an immature ductus arteriosus is so much more frequent than any other form of congenital heart disease. This does not mean that alternative diagnoses should be automatically excluded. However, in larger premature and full-term infants, sometimes a patent ductus arteriosus cannot be differentiated clinically from aortopulmonary window, truncus arteriosus, ventricular septal defect with aortic regurgitation, or arteriovenous fistula. A major problem may occur when there is severe heart failure with a markedly reduced cardiac output and sympathetic vasoconstriction; the peripheral pulses may not be bounding, the murmur may be soft and not continuous, and the precordium may not be hyperactive. After appropriate therapy for left ventricular failure, the classic physical findings usually reappear.

Outcome

In the full-term infant with a patent ductus arteriosus, spontaneous closure may occur, but much less commonly than in the premature infant. Medical management, if needed, should be instituted, and at a convenient time surgical closure should be done. Even if there is no heart failure, there are 2 reasons to close a patent ductus arteriosus. If there is marked pulmonary hypertension as a result of a large communication, the danger of the development of pulmonary vascular disease necessitates closure, preferably before 6 to 8 months of age. In the older child with a small patent ductus arteriosus, closure should still be advised in view of the risk of infective endocarditis, even though this risk is very low. Transcatheter closure with a coil is satisfactory if the diameter of the ductus is below 3 mm, but larger ductuses can often be closed by devices such as the Amplatzer ductus occluder. Some ductuses still need surgery, either because they are too large for a catheter-introduced device or, conversely, in a premature infant whose blood vessels are too small to accept the large catheter needed to introduce coils or other devices. Surgery can be done safely by open thoracotomy or by thoracoscopy and may be a much shorter procedure than interventional catheterization.

Aortopulmonary Fenestration

Aortopulmonary fenestration or window, caused by failure of formation of the base of the spiral septum, generally produces a large aortopulmonary communication just above the semilunar valves. The pulses are typically bounding or collapsing, like those of a large patent ductus arteriosus. However, the murmur more closely resembles that of a high ventricular septal defect in that it is generally not continuous, has a rough, often crescendo-decrescendo character, and is heard maximally along the left sternal border in the third and fourth intercostal spaces. The diagnosis can be made by 2-dimensional echocardiography and confirmed by cardiac catheterization and angiocardiography. Surgical closure during cardiopulmonary bypass is corrective. Occasionally a small opening can be closed by interventional catheterization.

Anomalous Origin of Left Coronary Artery

See below for a detailed discussion.

Anomalous Origin of Pulmonary Artery Branch from Ascending Aorta and Lobar Sequestration

Anomalous origin of a pulmonary artery branch from the ascending aorta has been called hemitruncus arteriosus, but it is not related embryologically to persistent truncus arteriosus because the embryonic truncus arteriosus septates normally in the former defect, with the opposite pulmonary artery arising from a normal pulmonary valve and main pulmonary artery. Most often, the right pulmonary artery arises from the aorta. In lobar sequestration, a portion of the lung, usually a lobe or part of a lobe, gets its arterial blood supply from an abnormal artery arising from the aorta. The involved pulmonary artery does not communicate with the main pulmonary artery. Pulmonary vascular resistance and the resistance offered by the communicating vessel control the flow into the lung or portion of lung. The clinical presentation in children with these lesions also depends on the magnitude of the shunt and will be similar to that found with a patent ductus arteriosus, but congestive heart failure is more common in the anomalous pulmonary artery because it is equivalent to a large patent ductus arteriosus. However, the murmur, often continuous, may be better heard more laterally or even in the back.

One important feature of the anomalous pulmonary artery circulation is that the normally arising pulmonary artery carries the total right ventricular output, which is the total systemic venous return. Normally this flow is distributed between the 2 pulmonary arteries, but with an anomalous pulmonary artery all the systemic venous return passes through about one half of the total number of lung vessels. Pressure in the normally arising pulmonary artery is generally normal; therefore, the risks of subsequent pulmonary vascular disease are similar to those in children with atrial septal defects and a pulmonary blood flow about twice normal. However, with an associated left-to-right shunt, blood flow to the normal lung is more than doubled; thus, there may be pulmonary hypertension and subsequent pulmonary vascular disease. The lung supplied by the abnormally arising vessel is at risk not only from increased flow but also from increased pressure, because this lung is perfused at systemic pressure less the pressure decrease offered by the channel. If the abnormally arising pulmonary artery is adequately developed, implantation into the main pulmonary artery can be done. If a significant portion of lung is involved in lobar sequestration, a lobectomy is indicated.

Unilateral Pulmonary Artery

Although this is not a lesion with a left-to-right shunt, it resembles an anomalous pulmonary artery from the ascending aorta. The right or the left pulmonary artery may be congenitally absent, either isolated or with other congenital cardiac defects, but most often, the artery arose from a ductus arteriosus that subsequently closed. A unilateral pulmonary artery, either left or right, has the same incidence when these are isolated lesions and when they are associated with most cardiac defects; however, if there is a patent ductus arteriosus, then usually the right pulmonary artery is absent, and in the tetralogy of Fallot, the left artery is almost always missing. The lung on the affected side is hypoplastic and supplied by bronchial arteries if the artery is truly absent, so that the chest roentgenogram shows a small hemithorax, no hilar pulmonary artery, and often a diffuse reticular pattern of bronchial collaterals. Because ventilation can still take place on that side, there is wasted ventilation and usually dyspnea on effort.

The chief importance of the lesion is its tendency to produce pulmonary hypertension and pulmonary vascular disease in all except those with the tetralogy of Fallot. Because there is only one pulmonary artery, it receives the total right ventricular output, just as in the anomalous origin of the pulmonary artery from the ascending aorta. Therefore, even if there are no other lesions, that lung receives twice its normal blood flow; if there are left-to-right shunts in addition, it gets more than this. In infancy, before pulmonary arterial muscle has regressed, this increased flow leads to hypertension and can eventually cause severe pulmonary vascular disease, which has been reported in 18% of patients with no other lesions and 88% of those with cardiac lesions.

Diagnosis is made by angiography or magnetic resonance imaging. Treatment is directed at repairing the associated defects and avoiding anything that might affect the pulmonary vessels of the normal lung (eg, living at high altitude or taking contraceptive pills).

Sinus of Valsalva Fistula

Rupture of a sinus of Valsalva into one of the cardiac chambers is secondary to an aneurysm due to a structural abnormality in the sinus. Most commonly these changes involve the anterior (right coronary) aortic valve sinus, and the ruptured aneurysm subsequently produces a communication from the right coronary sinus into the right ventricle or right atrium. Less commonly, rupture involves the noncoronary or the left coronary sinus; rupture into the left atrium or ventricle is discussed below in Aortic Regurgitation. The aneurysmal dilatation of the sinus that precedes rupture is often associated with a ventricular septal defect, a combination particularly common in persons of Asian descent. Connective-tissue disorders such as Marfan syndrome may also have associated aneurysmal dilatation of the aortic sinuses, but these do not rupture. Small fistulas may occur after infective endocarditis, but more extensive rupture usually occurs after trauma or spontaneously with progressive weakening of the sinus. Acute rupture, although more common in young adults, does occur in children. At the time of rupture, there frequently is an episode of acute chest pain and dyspnea, with sudden onset of a murmur and congestive heart failure; however, a more insidious onset has been described. With rupture into the right ventricle, the physical signs resemble those of a patent ductus arteriosus, with a loud continuous superficial murmur along the left sternal border, but with the addition of an increased right ventricular volume load. With rupture into the right atrium, this lesion will behave like an obligatory shunt, and the features are those of a patent ductus arteriosus and an atrial shunt combined. The diagnosis can be made by 2-dimensional echocardiography, including Doppler and contrast echocardiograph. Accurate differentiation from other lesions may require cardiac catheterization and angiocardiography. Surgical closure of the fistula can be done with cardiopulmonary bypass.

Congenital Coronary Arteriovenous Fistula

In this lesion, a fistula usually passes from one of the coronary arteries directly into the right ventricle (the most common site) or into the right atrium (either directly or through the coronary sinus). Communications with the left ventricle, left atrium, or pulmonary artery are much less common, except for small coronary-pulmonary fistulas that are of little importance.

The most striking clinical feature is a continuous murmur superficial in character and heard best along the lower left sternal border. The murmur is generally maximal in diastole and has very high-pitched components. Ventricular hyperactivity and a mid-diastolic rumble depend on the magnitude of shunting, which is not usually great enough to cause congestive heart failure. A continuous thrill may be palpable. Occasionally the fistula causes a myocardial steal and ischemic symptoms. The diagnosis can be made by 2-dimensional echocardiography with Doppler and contrast echocardiography, but the specific diagnosis may require cardiac catheterization and angiocardiography. Treatment is usually performed by a catheter approach. Coils or occlusive devices can be placed relatively safely because most fistulas enter the right atrium or ventricle, so that embolization, if it occurs, is to the lungs, and the coil can easily be retrieved. Care needs to be directed toward not occluding normal coronary arteries. Surgery is occasionally necessary when the fistula is extremely large or proximal.

Systemic Arteriovenous Fistula

Placental arteriovenous fistulas may produce a large increase in fetal cardiac output, particularly in descending aortic blood flow. Although the fistula is no longer present after birth, residual signs may remain in the neonate. These include peripheral edema, cardiomegaly, and a dilated descending aorta.

The most common sites for large arteriovenous communications in children are intracranial, hepatic, or in the extremities. However, fistulas have been described between internal mammary vessels or other major systemic arteries and their related veins, and with more frequent use of 2-dimensional echocardiography and color Doppler, these are being encountered more frequently. They may be seen as part of Rendu-Osler-Weber syndrome (hereditary hemorrhagic. telangiectasia). They can also be traumatic in origin, most commonly between renal vessels after needle biopsy of the kidney and in the femoral triangle after needling of the femoral vessels.

Because these lesions are obligatory left-to-right shunts, the hemodynamic and clinical features depend on the size of the communication and thus its resistance to flow. The majority of systemic arteriovenous fistulas are small and so do not produce major hemodynamic changes. The exceptions to this are hepatic or intracranial arteriovenous fistulas, particularly those that involve the great vein of Galen or its tributaries. Fistulas can be large and single, multiple, or even resemble cavernous hemangiomas.

Certain clinical features are common to all types of arteriovenous fistulas: a systolic or continuous murmur over the site of the fistula, occasionally a pulsatile mass, and distended and sometimes pulsatile veins draining the region of the fistula. Increased limb size and swelling may occur with peripheral arteriovenous fistulas. Hepatic arteriovenous fistulas generally do not involve one feeder vessel but are usually hemangiomatous.

Intracranial arteriovenous fistulas usually produce the most severe hemodynamic changes because they involve vessels of large caliber and the left-to-right shunt is often large. In early infancy, they may produce severe congestive heart failure, and they are among the few cardiovascular lesions that produce hydrops fetalis or severe congestive failure in the first days after birth. Clinically, they have continuous murmurs over either side of the skull and bounding carotid pulses and distended jugular veins. The superior vena cava is generally markedly dilated on chest radiograph, and there is significant right and left ventricular volume overload. Peripheral pulses are bounding and even collapsing, unless heart failure is so marked that all pulses except the carotids are feeble. If the shunt is not large, cardiovascular manifestations may be mild, and neurologic sequelae dominate the clinical picture. Contrast 2-dimensional echocardiography with Doppler is helpful in diagnosis, but the definitive diagnosis of these lesions may require cardiac catheterization and angiocardiography. Currently arterial embolization is the treatment of choice, but significant neurological sequelae often remain.

Hepatic arteriovenous fistulas may present with congestive heart failure, but like most other hemangiomatous lesions tend to involute in the first year. Involution may be facilitated by giving steroids. Conservative or medical management is appropriate for many of them, especially because the lesions may extend diffusely throughout the liver. If, however, they have uncontrollable congestive heart failure, then the surgeon can either ligate the hepatic artery or, if the lesion is localized, perform a lobectomy.

Ventricular Septal Defect

Congenital defects of the interventricular septum are the most common of all congenital heart lesions, accounting for approximately 30% to 60% of all full-term patients with congenital heart malformations; this percentage is equivalent to 3 to 6 of every 1000 live births. This excludes the 3% to 5% of neonates with tiny muscular ventricular septal defects that usually close within the first year. A ventricular septal defect usually occurs as an isolated abnormality but may be associated with other congenital cardiac malformations. In view of the pattern of blood flow in the heart and great vessels of a fetus with a ventricular septal defect, with diversion of blood from the aortic isthmus, narrowing of the aortic isthmus or true coarctation should always be considered when an infant with a ventricular septal defect has severe heart failure. Ventricular septal defects are also common in corrected transposition of the great arteries, in which systemic atrioventricular valve regurgitation and complete heart block are also frequent. They are always present in a truncus arteriosus communis and in a double-outlet right ventricle that, in the absence of pulmonic stenosis, has the clinical features of an isolated ventricular septal defect.

An isolated ventricular septal defect may occur anywhere in the interventricular septum. At birth, about 90% of these defects occur in the muscular septum, but because these usually close spontaneously within 6 to 12 months of birth, the membranous septum becomes the most common site after infancy. Defects vary in size from minute openings to almost complete absence of the interventricular septum (a common ventricle). Most muscular (except multiple, “Swiss cheese”) and perimembranous defects have a high chance of spontaneous closure, unlike large inlet subtricuspid defects, subarterial outlet defects (subaortic as in tetralogy of Fallot or large subpulmonic (as in “supracristal” defects), or doubly committed subarterial ventricular septal defects. Spontaneous partial closure of subpulmonic or doubly committed subarterial defects often involves prolapse of the aortic valve cusp into the defect with development of aortic regurgitation; this form of defect occurs in 5% of whites but in about 35% of Japanese and Chinese. Spontaneous closure of perimembranous defects often is associated with ventricular septal pseudoaneurysm formation; early detection of such an aneurysm indicates a high likelihood of closure.

Clinical Manifestations

The pathophysiology of left-to-right shunting through a ventricular septal defect involves left and right ventricular volume overloads because the extra volume of the left-to-right shunt passes into the right ventricle before passing into the pulmonary artery.

The systolic murmur of a ventricular septal defect is generally harsh and of the regurgitant or plateau type. With a small shunt, the murmur may be heard only in early systole; as the shunt increases, however, the murmur becomes holosystolic and ends at the aortic component of the second sound. The intensity of the murmur is not necessarily related to the size of the defect, and loud murmurs may be heard with hemodynamically insignificant defects (maladie de Roger). Loud murmurs are usually associated with systolic thrills. The murmur is generally heard best at the lower left sternal border, and it radiates throughout the precordium, but maximally toward the subxiphoid area. However, with a high subpulmonic ventricular septal defect, the maximal intensity may be at the middle to upper left sternal border, with radiation to the right of the sternum. Occasionally the murmur of a very small defect has a crescendo-decrescendo high-pitched almost whistling quality and must be distinguished from an innocent murmur. When the left-to-right shunt is large enough to produce a ratio of pulmonary flow to systemic flow higher than 2:1, a mid-diastolic rumbling murmur may be audible at and inside the apex, and a third sound may appear. As the shunt increases, so does precordial activity. The peripheral arterial pulses give important information about shunt size. If there is a very large shunt that is well above the cardiac output, the left ventricle has to contract forcefully and rapidly to eject the increased stroke volume during a normal systolic interval. This is perceived in the radial and brachial arteries. Unlike in the patent ductus arteriosus, the volume of blood entering the aorta at each stroke is normal, and in diastole there is no rapid runoff through the ductus and less peripheral vasodilatation because baroreceptors are not stimulated. Thus, the rapid fall to a low diastolic pressure is not seen with a ventricular septal defect, but the rapid rise of the pulse gives the impression of a collapsing pulse.

If the defect is small or medium in size, there is no pulmonary hypertension, and the pulmonic component of the second sound is either of normal or minimally increased intensity. If there is pulmonary hypertension, the pulmonic component of the second sound is accentuated. With a small or moderate-sized shunt, the chest roentgenogram shows no or slight increase in left ventricular and left atrial size and pulmonary vascular markings. As the volume of shunting increases, cardiac enlargement and pulmonary vascularity also increase, and pulmonary edema may be seen. Because the shunt is at the ventricular level, the ascending aorta is not dilated. The electrocardiogram is normal if the defect is small; it shows increasing left ventricular hypertrophy as the left-to-right shunt increases, and when there is much right ventricular hypertension, right ventricular hypertrophy is added. A 2-dimensional echocardiogram can be used to show the size and position of the ventricular septal defect. Doppler with imaging techniques can localize the defect by detecting disturbed flow in the right ventricle, and color Doppler flow mapping can demonstrate single or even multiple defects. The Doppler measurement also allows measurement of the pressure gradient across the defect; the higher the gradient, the smaller the defect. In the most severe form of ventricular septal defect, single ventricle complex, magnetic resonance imaging may help to delineate the anatomy.

If there is a large left-to-right shunt, there are clinical signs and symptoms of volume overload and cardiac failure. In full-term infants, this occurs most commonly between 2 and 6 months of age, but it may occur earlier in premature infants. Although the left-to-right shunt should generally be greatest between 2 and 3 months of age, when pulmonary vascular resistance has dropped to its lowest level, congestive heart failure occasionally occurs in term infants under 1 month of age. In these infants, the ventricular septal defect is often associated with anemia, or a significant left-to-right shunt at the atrial or ductus arteriosus levels, or coarctation of the aorta. In addition, infants who have double-outlet right ventricle with ventricular septal defect are at risk of developing congestive failure earlier than expected. This is possibly because in fetal life the pulmonary vasculature is perfused with blood that has a higher oxygen tension than normal; thus, there may be unusually low pulmonary vascular resistance after birth.

Management

Isolated ventricular septal defects are the most common types of congenital heart disease, so that all pediatricians need to know how they can be managed. The decision tree is shown in Figure 484-1, and the circled numbers in the table are as follows:

1. 1. About 3% to 5% of all live-born babies have small muscular ventricular septal defects, most of which close spontaneously within the next 6 to 12 months. It is neither practical nor reasonable to obtain echocardiograms in all of them, provided that there appears to be nothing more than a small ventricular septal defect, the heart is quiet, and there are no symptoms. Note that a neonate with a large ventricular septal defect usually has no murmur in the newborn nursery; a large defect with a small shunt across it because of a high pulmonary vascular resistance produces little turbulence. In fact, a typical ventricular septal defect murmur heard in the newborn nursery is almost certainly caused by a small defect.

   2. Because defects in the perimembranous or muscular portions of the septum have a high incidence of spontaneous closure, it is appropriate to treat them medically for up to 1 year in the hope that surgery can be averted. Several different mechanisms may be responsible for spontaneous closure of a ventricular septal defect. These include growth and hypertrophy of the muscular portion of the defect, formation of a membranous diaphragm (from intimal proliferation), apposition of the septal leaflet of the tricuspid valve against the defect, or prolapse of the aortic valve cusp, which can lead to aortic regurgitation. When the defect is getting smaller, the systolic murmur may first increase in intensity, but with progressive decrease in size, the murmur becomes softer, and when the defect is extremely small, the murmur becomes shorter and acquires a crescendo-decrescendo high-pitched whistling quality that often portends complete closure. Spontaneous closure may eventually occur in up to 70% of patients, and many of these closures occur by 3 years of age. Most of the closures occurred with small hemodynamically insignificant defects, but even the largest defects can close spontaneously. In a further 25%, the defect becomes smaller but may not close completely; however, the hemodynamic effects are significantly reduced. Because of these statistics, if the defect seems to be becoming smaller, surgical correction should be delayed in the hope of spontaneous closure.

   Figure 484-1 also shows reasons for considering early surgery without waiting for the defect to close spontaneously.

   3. Some patients respond well enough to medical treatment to go home, but return a week or so later in more severe congestive heart failure. Treatment regimens and doses are adjusted, they improve, and they go home, but the cycle is repeated. These children should be regarded as treatment failures, and they require closure of the defect. Children with trisomy 21 appear to get early pulmonary vascular disease, so their surgery should not be deferred if the defect remains large.

   4. Severe social problems are rare reasons for early surgery. These include inability of the parents to bring the child for frequent medical supervision because of distance from the doctor or negligence. In addition, some of these infants are very difficult to manage. They require 2-hourly feeds and consume so much attention that other children in the family are neglected; marriages may even be threatened.

   5. Although all infants with large ventricular septal defects grow poorly, with weights usually below the fifth percentile and heights below the 10th percentile, catch-up growth usually occurs once the defect is closed (spontaneously or after surgery). In most of these infants, the growth of head circumference is normal, but in a few head growth falls off rapidly by 3 or 4 months of age. Head growth will return to normal if the defect is closed at this time but fails to catch up if surgery is delayed more than 1 to 2 years.

   6. If the patient does not need early surgery for one of the reasons mentioned above, it is appropriate to wait for about 12 months in the hope that the defect will close or become smaller.

   7. If the shunt remains large after 1 year of age, there has to be a reason for not closing a large ventricular septal defect because of the increasing risk of irreversible pulmonary vascular disease. By 2 years of age, about 33% of these children have irreversible pulmonary vascular disease.

   8. If the left-to-right shunt becomes smaller, there will be clinical improvement, manifested by decreasing cardiac hyperactivity and heart size, diminishing intensity and eventual disappearance of the mid-diastolic murmur, decreasing intensity and changing character of the systolic murmur, lessening and then disappearance of tachypnea, improved appetite and growth, and lessening demand for drug therapy. It is crucial not to be misled into thinking that this improvement necessarily indicates a smaller VSD, because it might also reflect the development of pulmonary vascular disease or, less often, infundibular stenosis. Echocardiography and perhaps cardiac catheterization are mandatory to make decisions about future management at this stage.

   9. In most patients with a ventricular septal defect, severe pulmonary vascular disease does not occur until after 1 year of age. However, it can occur earlier, and this will be indicated by a decrease in the left-to-right shunt, a finding that indicates the need for further studies. If obstructive pulmonary vascular disease occurs, there is often little or no left-to-right shunting and no significant right-to-left shunting for several years. (See Chapter 492) However, generally by 5 to 6 years of age, there is increasing cyanosis, particularly during exercise (Eisenmenger syndrome). As severe pulmonary hypertension develops, the main pulmonary artery segment becomes markedly dilated, and the peripheral pulmonary vascular markings on the chest roentgenogram decrease. Obstructive pulmonary vascular disease may progress rapidly in some infants and become irreversible by the age of 12 to 18 months; this should never be allowed to occur. Any doubt as to the cause of any change in clinical status should be investigated by 2-dimensional echocardiography with Doppler or if necessary by cardiac catheterization, and there is good reason to consider routinely recatheterizing children with large ventricular septal defects at 9 to 12 months of age to detect early pulmonary vascular disease that is not clinically apparent. Once irreversible pulmonary hypertension occurs, treatment with prostaglandin analogs (eg, Flolan), endothelin receptor blockers (eg, bosentan), or phosphodiesterase inhibitors (eg, sildenafil) may ameliorate the disease, but hemoptysis and congestive heart failure eventually cause death, usually in the third or fourth decades. The only definitive treatment is lung transplantation.

   10. Infundibular hypertrophy generally develops fairly rapidly, and there may be only a short period in which the left-to-right shunting is present. Soon thereafter, there will be cyanosis, initially on exercise only but then persistently, and the features of the tetralogy of Fallot can develop. In those infants who develop right ventricular outflow obstruction, the incidence of spontaneous closure of a ventricular septal defect is low; a right-to-left shunt can be further complicated by cerebral thrombosis, embolism, or abscess, and the development of infundibular hypertrophy leads to more difficult surgical repair, so that closure of the defect and infundibular resection, if necessary, should be considered early.

Primary surgical closure of the defects can be done with very low mortality. If primary closure is not feasible because of multiple muscular defects or other complicating factors, then banding the pulmonary artery will decrease the left-to-right shunt, reduce pulmonary arterial blood flow and pressure, and relieve congestive heart failure. Banding has its own complications, and removal of the band when the defect is closed later adds to the mortality of the procedure.

Muscular defects, especially if multiple, lead to difficult surgery. From a right ventriculotomy, the masses of hypertrophied trabeculae are daunting and make the defect(s) difficult to find. Although a left ventriculotomy simplifies surgery, a large incision in the systemic ventricle should be avoided. Some surgeons cut away all the right ventricular trabeculae to make closing the defect easier, and others suture all the trabeculae together to close the exit holes. Because of the difficult surgery, closing the muscular defect by catheter introduction of an Amplatzer device is being used more often. Some catheterization procedures are very lengthy, and an alternative is to use a hybrid method in which a surgeon performs a small thoracotomy and the Amplatzer device is inserted more directly through a trocar. Some cardiologists have even used similar devices for nonsurgical closure of perimembranous ventricular septal defects, but this procedure has more risk of producing complete atrioventricular block and of damaging the aortic valve, and it is still considered experimental.

Consequence and Complications

In several infants with significant reductions in left-to-right shunts caused by spontaneous closing of the ventricular septal defects, mid- to late systolic clicks have become audible. In these children, aneurysmal dilatation of the thin membranous septum or tricuspid valve tissue that has grown to close the defect has occurred, with bulging of pseudoaneurysm into the right ventricle. A small opening often present at the apex of the pseudoaneurysm allows a small left-to-right shunt. Normally, the defect closes, and the pseudoaneurysm slowly shrinks, but rarely it may enlarge progressively. These pseudoaneurysms can be demonstrated by echocardiography.

A number of infants have developed progressive aortic insufficiency associated with ventricular septal defect, particularly if it is subarterial. There is prolapse of an aortic valve leaflet with dilatation of the aortic valve sinus, and rupture of the aortic sinus or cusp may occur. The development of insufficiency has been attributed to stress on the unsupported aortic valve cusp and perhaps suction on it by the jet of the shunt passing through the defect. Even with a small ventricular septal defect, or one showing evidence of closure, aortic insufficiency requires surgical closure of the defect to prevent further prolapse. It may in fact be prudent to close subarterial ventricular septal defects even before evidence of aortic valve cusp involvement is apparent.

Infective endocarditis is an additional problem; rarely, it can occur even after spontaneous closure of the defect. If infective endocarditis involves the tricuspid leaflet sealing the ventricular septal defect, rupture may occur and produce a direct left-ventricular-to-right-atrial communication. Previously, antibiotic prophylaxis for infective endocarditis had been recommended for children with even small defects. Recently, however, the guidelines have been changed and prophylaxis is not recommended except for special circumstances, as discussed in Chapter 490.

L-Transposition of the Great Arteries

Ventricular inversion occurs when the primitive cardiac tube loops to the left instead of to the right during early development. The anatomic left ventricle is on the right side and connects the right atrium with its tricuspid valve to the pulmonary artery. The anatomic right ventricle on the left side receives oxygenated blood from the left atrium through a mitral valve and ejects into an anteriorly placed left-sided aorta. There is thus l-transposition of the great arteries and inversion of the ventricles, but the combination of discordant atrioventricular and discordant ventriculoarterial connections allows normal flow of venous blood to the lungs and arterial blood to the body; hence, the designation (physiologically) corrected transposition of the great arteries.

If there are no other lesions, people with this anomaly may live normal lives, but almost all have ventricular septal defects, many have pulmonic stenosis, some have an Ebstein-like malformation of the left-sided systemic tricuspid valve that produces left-sided atrioventricular regurgitation, and many have defects of atrioventricular conduction (particularly complete atrioventricular block). Those with normal conduction at birth develop complete heart block at a rate of 1% to 2% per year. The symptoms and signs depend on the severity and nature of these associated lesions.

In addition to the murmurs of ventricular septal defects or pulmonic stenosis, these patients characteristically have a loud second heart sound, often single, best heard at the upper left sternal border because of the high left anterior position of the aortic valve. The electrocardiogram may show atrioventricular conduction defects and will show right- or left-sided hypertrophy as appropriate for associated lesions. In about 80% of these patients, the electrocardiogram shows Q waves in right chest leads and no Q waves on the left, the pattern reflecting the activation of the septum from right to left.

Frequently, the chest roentgenogram indicates the diagnosis because the levoposed aorta produces a straight shoulder on the left heart border. Echocardiograms disclose the abnormal position of the great arteries, the morphology of the right- and left-sided ventricles, as well as another typical anatomic feature, the anteroposterior orientation of the ventricular septum.

Surgical correction of these lesions is more hazardous than correction of similar lesions without ventricular inversion. The abnormal conduction system increases the risk of surgically produced complete atrioventricular block when a ventricular septal defect is closed. Large coronary arteries often run across the outflow tract of the pulmonic ventricle, where an incision would have to be made. The pulmonary artery is very posterior, so that correcting pulmonic stenosis is difficult, particularly because the obstruction is seldom a valvar stenosis but more often a subpulmonic fibromuscular narrowing or else a mass of accessory tissue from the adjacent mitral valve. For these reasons, surgery is not advised if patients are doing well. If they deteriorate, then the pulmonary artery may be banded for a large left-to-right shunt, or else an aortopulmonary shunt is done to palliate severe cyanosis. Complete correction should be attempted only by a skilled surgeon and only after the risks have been fully assessed. Correction of the intracardiac and outflow tract defects can be done, but many patients eventually develop right ventricular failure and atrioventricular valve regurgitation that, because of the ventricular inversion, enters the left atrium and, if severe, causes pulmonary edema. The alternative is to perform an anatomic correction. In this procedure, not only are intracardiac defects corrected, but an arterial switch connects aorta and pulmonary artery to their correct ventricles and then an atrial baffle is performed to make pulmonary venous return enter the left ventricle. These procedures are surgically formidable, and although short- and mid-term results are quite good, the long-term outcome is unknown.

Atrial Septal Defects

Interference with the development of the septum primum at its lower margin, associated with abnormal development of the endocardial cushions, produces an ostium primum atrial septal defect with no inferior rim of atrial septal tissue. This lesion is generally associated with abnormalities of the mitral and tricuspid valves (which form from the endocardial cushions) as well as defective formation of the upper portion of the interventricular septum.

A second type of atrial septal defect is the ostium secundum defect. This is a defect in the central portion of the septum in relation to the foramen ovale; it results from inadequate closure of the central hole in the septum primum by the septum secundum and is more appropriately termed a fossa ovalis defect.

A third type of atrial septal defect is the sinus venosus defect—that is, in the superior portion of the atrial septum—and generally extends into the superior vena cava.

Incompetent (Patent) Foramen Ovale

With the onset of ventilation after birth, pulmonary venous return increases markedly, and left atrial pressure rises. The foramen ovale is therefore normally functionally closed by the membranous valve of the foramen ovale, apposed to the crista dividens and the lower portion of the septum secundum. Although typically functionally closed shortly after birth, the foramen ovale remains probe-patent or larger in 30% of people. When pulmonary vascular resistance does not fall normally after birth, the resultant pulmonary hypertension and increased right ventricular end-diastolic pressure and right atrial pressure often cause right-to-left shunting across the foramen ovale and systemic hypoxemia.

In some infants, although the normal atrial pressure relationships occur after birth, the valve of the foramen ovale does not completely cover the foramen, either because the valve is too short or because the foramen ovale has become enlarged and stretched in infants in whom left atrial pressure and volume are increased, as with patent ductus arteriosus, ventricular septal defect, or left ventricular outflow obstruction secondary to aortic stenosis or coarctation. Significant left-to-right shunting may occur through an incompetent foramen ovale when left atrial pressure is high. If the cause of the increased left atrial pressure is relieved, atrial shunting generally decreases or disappears. In some congenital heart defects, survival after birth depends on persistent patency of the foramen ovale. These defects include tricuspid, aortic, and mitral atresia and total anomalous pulmonary venous connection. In aortopulmonary transposition, a patent foramen ovale may be the only communication between the systemic and pulmonary circulations. Right-to-left shunting across the foramen ovale is also associated with right ventricular obstructive lesions, such as pulmonic stenosis, and with pulmonary hypertension, particularly in newborns.

Ostium Secundum Atrial Septal Defect

Ostium secundum defects vary in size from a small defect to one in which only a rim of atrial tissue separates the defect from the AV valves. Usually ostium secundum defects are isolated lesions, but some may be associated with partial anomalous pulmonary venous connection (usually draining the right lung) or pulmonic stenosis.

Small atrial communications are associated with small shunts. Such small defects are common at birth. Defects under 3 mm in diameter almost all close spontaneously, as do a high percentage of those from 3 to 6 mm diameter. On the other hand, some defects become larger.

Large defects are associated with large left-to-right shunts if there is a low inflow resistance of the right ventricle and a low pulmonary resistance. The effect of a large shunt at the atrial level is a marked increase in flow through the right atrium and right ventricle. This extra volume load is tolerated well by the right ventricle because it is handling the increased volume at a low pressure. Therefore, cardiac failure is unusual in infancy and, when it occurs, is generally precipitated by either a combination of defects or some other complication.

Children with large atrial septal defects are generally asymptomatic. However, when there is pulmonary hypertension because of congenital or acquired lung disease, especially in preterm infants, the atrial septal defect may contribute to the symptoms as well as to right-to-left intracardiac shunting. The increased right ventricular volume load causes precordial hyperactivity along the left sternal border. The first heart sound is normal, and the second heart sound is characteristically widely split, with absence of the normal respiratory variation in the width of splitting. Both components of the second sound are of normal intensity. Although fixed splitting of the second sound is characteristic in older children, this sign is occasionally absent, especially in infants or when the communication is not large.

Flow across the atrial septal defect is not associated with a murmur; however, a long systolic ejection murmur that is crescendo-decrescendo (ejection) in type is generally heard at the upper left sternal border as a result of increased flow across the right ventricular outflow tract and pulmonic valve. The murmur associated with atrial septal defects can usually be differentiated from an innocent pulmonary flow murmur, which is usually shorter, by the response to the Valsalva maneuver. When intrathoracic pressure is increased, systemic venous return is immediately reduced, right ventricular stroke volume decreases immediately, and the intensity of an innocent pulmonary flow murmur suddenly decreases. However, with a large atrial septal defect, the left-to-right shunt across the atrial communication maintains right ventricular stroke volume for several beats despite the decrease of systemic venous return; thus, there is little, if any, change in the intensity of the murmur in the first 3 to 4 beats. If the left-to-right shunt is fairly large, there is often a low-frequency, rumbling, early or mid-diastolic murmur caused by increased flow across the tricuspid valve and heard best at the lower left sternal border. A prominent third heart sound is often heard at the lower left sternal border.

The chest roentgenogram shows enlargement of the right atrium and ventricle and sometimes the outflow region of the right ventricle. The main pulmonary artery is dilated, and pulmonary vascular markings are increased. However, the relationship between prominence of the pulmonary vascularity and the magnitude of the left-to-right shunt is unreliable. The electrocardiogram generally shows right axis deviation with normal atrial complexes and normal conduction. There is right ventricular hypertrophy with a typical rsR or rSR pattern in the right precordial leads, and the S wave in the inferior leads is usually notched.

Two-dimensional echocardiography shows an increase in diastolic size of the right ventricle together with paradoxic motion of the interventricular septum. Other similar hemodynamic disturbances, such as partial anomalous pulmonary venous return and pulmonary or tricuspid regurgitation, may give similar findings. Septal dropout is often seen, indicating the site of the atrial septal defect, and color Doppler clearly demonstrates the flow patterns and often the defect. A negative shadow in the right atrium during contrast echocardiography can delineate the defect.

Persistent right-to-left shunting is unusual in ostium secundum defects, but transient right-to-left shunting is common after any Valsalva-like maneuver. However, with sinus venosus defects there may be right-to-left shunting from the superior vena cava into the left atrium because of deficiency in the upper part of the septum where it normally meets the superior vena cava, and slight arterial oxygen desaturation may be found. Infective endocarditis is rare in uncomplicated secundum atrial septal defects. Obstructive pulmonary vascular disease may occur, but not usually before the late second decade or third decade. This becomes evident by a decrease in the physical findings associated with the left-to-right shunt and later by right-to-left shunting. It is concern about the possible development of pulmonary vascular disease that generally leads to surgical closure of the communication. Atrial arrhythmias, especially atrial fibrillation or flutter (probably caused by atrial enlargement), congestive heart failure, mitral incompetence, and strokes from paradoxic embolization may occur in adult life, and these are added reasons for considering closure of atrial defects in children. However, several years after simple surgical closure, atrial arrhythmias still can develop. Nonsurgical closure using an umbrella-like device (Amplatzer, Helex, and others) manipulated into the defect by means of a large catheter are currently favored over surgical closure for all but the largest defects or those with an inadequate rim of tissue (see Chapter 499).

Ostium Primum Defects and Atrioventricular Septal (Endocardial Cushion) Defects

Ostrium primum and atrioventricular septal defects result from arrested or abnormal development of the endocardial cushions in the primitive atrioventricular (AV) canal; they range in severity from a small ostium primum atrial septal defect to a complete AV canal. The severity and type of anatomic defect depend on which endocardial cushions are involved and the stage of developmental failure. Because the cushions are involved in the development of both atrial and ventricular septa, as well as mitral and tricuspid valves, many different combinations of abnormalities in this region are found. They may occur as isolated lesions in otherwise normal infants; however, they may be associated with other congenital heart lesions (for example, tetralogy of Fallot, single ventricle) or other congenital abnormalities in trisomy 21 (Down), asplenia or polysplenia, and Ellis-van Creveld syndromes.

Fetal somatic development is essentially normal; however, there is a high incidence of secondary hemodynamic alterations in the aorta in this group of lesions. Subaortic outflow obstruction, although often of only minor severity, is common; when associated with the potential obligatory shunt in utero, it may result in significant alterations in the patterns of blood flow during fetal life. Therefore, aortic isthmus narrowing and juxtaductal coarctation are found in many infants with this defect.

Ostium Primum Defect

Ostium primum defect is the most benign form of endocardial cushion defect; it is also termed partial atrioventricular canal defect. The central portion of the atrial septum in the region of the mitral and tricuspid valve rings is absent, and the defect is usually large. The anterior (or septal) mitral valve leaflet is displaced and usually cleft. The tricuspid valve is generally not involved but may also have a small cleft in the septal leaflet. The magnitude of the atrial left-to-right shunt is controlled by the same mechanisms in ostium primum as in secundum atrial septal defects. The clinical features are similar and include right ventricular hyperactivity, increased pulmonary blood flow, and a widely split second sound. In addition to the right ventricular outflow murmur and the tricuspid mid-diastolic flow murmur, murmurs of mitral or tricuspid regurgitation, or both, may be present if significant clefts in these valves are present. However, marked regurgitation is unusual, particularly in infancy and early childhood. The electrocardiogram characteristically shows left axis deviation, generally in the 20° to 60° range, and right ventricular hypertrophy with an rsR' pattern in right precordial leads. Chest roentgenographic findings depend on the magnitude of left-to-right shunting. Two-dimensional echocardiography and color Doppler flow mapping usually clearly delineate the anatomy. Congestive heart failure and arrhythmias occur, usually in late teenage or early adult life.

Surgical closure of the primum defect and repair of the cleft mitral valve has low risk and high effectiveness, but postoperative subaortic stenosis is common. Some of these patients develop severe hemolysis from red cell trauma if a small deficiency in the mitral valve leaflet directs a high-pressure jet at the atrial patch. At times hemolysis improves, but some patients require reoperation to abolish the hemolysis.

Complete AV Canal Defect

Complete atrioventricular (AV) canal defects involve failure of development of separate tricuspid and mitral valve rings. In addition to the ostium primum defect, there is a ventricular septal defect in the posterior portion of the interventricular septum and clefts in the septal leaflets of both the tricuspid and mitral valves. The anterior and posterior segments of each septal leaflet are not separated (as in normal development) but join each other through the defect, so that in the most severe form there is a large common anterior mitral-tricuspid valve leaflet as well as a smaller common posterior mitral-tricuspid valve leaflet. The chordae tendineae attach these common valves to the crest of the ventricular septum, the right side of the septum, or occasionally the right ventricular free wall. The earlier the stage of arrested development of the endocardial cushions has occurred, the larger the ventricular septal defect and the more primitive the development of the AV valves. Although the most severe form may occur as an isolated defect, it may be associated with other complex anomalies such as asplenia or polysplenia syndromes and single ventricle.

In general, the more severe or primitive the defect, the more marked the clinical manifestations. The ventricular septal defect behaves like any other ventricular septal defect in producing a left ventricular volume load and, if it is large, pulmonary hypertension and a right ventricular pressure load. The characteristic murmur of a ventricular septal defect will be present, as will a mid-diastolic rumble caused by increased pulmonary venous return with increased diastolic flow across the mitral valve. If the cleft in the mitral valve is significant, mitral regurgitation may be present, and an apical pansystolic blowing murmur may be heard. The mid-diastolic rumble will then be further accentuated by the even larger flow across the mitral valve, and left ventricular enlargement will be more prominent. The ostium primum defect portion of the complete canal will present with physical findings similar to those in an isolated atrial septal defect; these include right ventricular volume overload, a tricuspid diastolic flow rumble, and a right ventricular outflow murmur. Should tricuspid regurgitation be present, a pansystolic blowing murmur in the tricuspid area and systolic pulsation of the jugular veins may be evident, and the increased flow across the tricuspid valve will accentuate the mid-diastolic murmur. Both the atrial and ventricular shunts are dependent. However, often the cleft in the misplaced mitral valve allows ventricular blood to pass through it and the ostium primum defect to enter the right atrium, so that there is an obligatory shunt from left ventricle to right atrium. There may at times be minor right-to-left shunting and mild cyanosis.

Heart failure often occurs by 2 months after birth. However, symptoms may develop very early in infancy if there is an obligatory large left-ventricle-to-right-atrium shunt or with significant AV valve dysfunction; an additional defect, such as a patent ductus arteriosus, may also lead to early symptoms. These symptoms are primarily related to severe congestive heart failure and include tachypnea, sweating, and difficulty with feeding. Systemic cardiac output is generally low, and the infant then has poor pulses, tachycardia, hepatomegaly, and peripheral pallor. Marked cardiomegaly is common.

As with ostium primum defects, the electrocardiogram shows left axis deviation (superior axis), but in most complete AV canal defects it is even more negative, in the range of 60° to 150°. The frontal-plane vector loop is counterclockwise. The P-R interval is often prolonged. Ventricular and atrial hypertrophy depend on the level of maximal shunting and the amount of AV valve regurgitation. The left axis deviation is not pathognomonic of an atrioventricular septal defect; it may also be found with double-outlet right ventricle, with tricuspid or pulmonary atresia, or even in normal children. The absence of left axis deviation does not exclude the diagnosis of an atrioventricular septal defect but is strongly against it. Chest roentgenographic findings depend on the level of shunting and the amount of AV valve regurgitation. Two-dimensional echocardiography and Doppler color flow mapping yield specific anatomic information and permit detection of differences between incomplete and complete forms of this defect. Magnetic resonance imaging may contribute to anatomic detail.

Untreated infants with this defect either die from congestive heart failure or are at high risk of developing obstructive pulmonary vascular disease from the severe pulmonary hypertension and large left-to-right shunt, so that early surgery is advisable. Many infants have poor responses to vigorous medical management, although this may buy a little time. Complete surgical repair of these lesions can be done in infancy with a mortality rate of about 5% to 10% providing the 2 ventricles are about of equal size. Infants with Down syndrome tend to have a more favorable anatomy for correction. The availability of transesophageal echocardiography during surgery adds to the effectiveness of surgery, particularly when mitral regurgitation is a major component. If the ventricles are unbalanced, then some form of single ventricle repair can be done. Postoperative hemolysis is a complication.

If for some reason complete correction is not appropriate, intractable cardiac failure may be improved by pulmonary artery banding, which will increase the outflow resistance of the right ventricle and so decrease the amount of dependent shunting. However, in most infants with complete AV canal defects, the large left-ventricle-to-right-atrium shunt or AV valve regurgitation will be unaffected by pulmonary artery banding.

Partial Anomalous Pulmonary Venous Connection

Partial anomalous pulmonary venous connection without an associated atrial septal defect is rare. The anomalous pulmonary veins almost always drain either the complete right lung or a portion of it, and they may connect with the superior vena cava or directly with the right atrium. In addition, there is a specific entity (scimitar syndrome) in which the pulmonary veins from the lower lobe and sometimes the middle lobe of the right lung drain by a common channel into the inferior vena cava. Associated with this is underdevelopment as well as lobar sequestration of that portion of the lung. The chest roentgenogram in scimitar syndrome is typical, and the anomalous vessel is generally seen easily. The clinical presentation of these lesions resembles that of secundum atrial septal defects, except that the second heart sound is generally normally split. Partial anomalous pulmonary venous connection, when associated with an atrial septal defect, does not generally contribute any specific clinical features. If the right side of the heart is dilated, surgical baffling of the anomalous veins into the left atrium achieves excellent results.10-52

Each of the cardiac valves may be affected pathologically so that the valve orifice is unguarded, and blood regurgitates across it from the higher-pressure to the lower-pressure region. In each condition associated with regurgitation of the left or right side of the heart, the left or right ventricle is dilated proportionally to the degree of regurgitation.

The severity of the lesion can be evaluated by assessing the effect of the regurgitant volume on the cardiac chamber or great artery on either side of the regurgitant valve. This can be done simply by the history, physical examination, electrocardiogram, and chest x-ray.

The possible etiologic factors and anatomic cause of the particular valvar abnormality leading to regurgitation must be sought.

With the availability of echocardiography, more precise assessment of hemodynamics and anatomy can be obtained. This diagnostic technique, however, is often unnecessary at the initial evaluation or at each subsequent visit if the physician can apply less-expensive basic clinical skills and diagnostic techniques.

Aortic Regurgitation

The primary finding of aortic regurgitation is a high-pitched, early diastolic murmur that starts at the aortic component of the second heart sound. The length and loudness of the murmur increase with the severity of regurgitation.

Most children with this condition are asymptomatic, but if it is at least moderately severe, they have fatigue on exercise. Those with either significant chronic regurgitation or acutely developing regurgitation may develop congestive heart failure. With acute onset of aortic regurgitation, as from ruptured sinus of Valsalva (discussed below), symptoms develop abruptly.

With moderate or severe aortic regurgitation, the pulse pressure is widened, the systolic pressure being elevated by the augmented left ventricular stroke volume (cardiac output plus regurgitant volume), and the diastolic pressure is lowered because of “runoff” into the left ventricle as well as baroceptor-induced peripheral vascular vasodilatation. On auscultation, an aortic systolic ejection murmur is frequently present from the augmented forward flow across the aortic valve or structural abnormality of the valve. There may be at the apex a low-pitched, mid-diastolic murmur (Austin Flint murmur) attributed to the regurgitant aortic jet striking the anterior leaflet of the mitral valve, making it vibrate.

An electrocardiogram may show tall R waves in the left precordial leads from left ventricular dilatation. T waves become flat or inverted in these leads if coronary perfusion is impaired by low aortic diastolic pressure.

Chest x-rays are normal if regurgitation is mild but show cardiac enlargement with a left ventricular contour when moderate or severe regurgitation is present. The ascending aorta may appear prominent along the upper right side of the mediastinum from either the large stroke volume or anatomic features secondary to the condition causing the regurgitation, such as Marfan syndrome or aortic stenosis.

The echocardiogram is very helpful in assessing the hemodynamics and anatomic causes of this regurgitation. The regurgitant jet can be identified and assessed by color echo Doppler; the breadth and extent of the jet correlate with the degree of regurgitation. In addition, measurement of left ventricular dimensions can assess the regurgitant volume, and the ejection or shortening fraction assesses the ventricular response to the volume overload. The appearance of the aortic valve, surrounding structures, and ascending aorta is critical to determine the underlying cardiac abnormality or etiologic factor.

Regurgitation from the aorta into the left ventricle results from a variety of congenital or acquired cardiac conditions, which occasionally coexist.

Congenital aortic stenosis usually occurs secondary to a bicuspid valve that during childhood may develop minimal aortic regurgitation, recognizable only as a soft murmur and minimal regurgitation on echo Doppler. The usual treatment of moderate or severe aortic stenosis is by valvotomy or valvoplasty. After either procedure, the degree of regurgitation increases, but rarely enough to result in symptoms or more than minimal hemodynamic disturbance, except in an occasional patient following balloon valvoplasty.

In membranous subaortic stenosis, the jet through the membrane, which is located slightly below the aortic valve, strikes one of the aortic valve cusps, distorting and thickening it, so it may become mildly regurgitant.

Sinus of Valsalva aneurysm results from separation between the aortic media and the heart at the level of the annulus fibrosis, as the aneurysm is below the level of the valve. The aneurysm can occur in any of the 3 aortic sinuses and may rupture into the adjacent cardiac chamber (see Sinus of Valsalva above). With progressive prolapse, aortic regurgitation develops. If the aneurysm ruptures, congestive cardiac failure and a murmur of aortic regurgitation develop abruptly.

Aortico–left ventricular tunnel is a rare condition in which a vascular-like structure arises above the aortic valve and passes through the ventricular septum to the left ventricle. This results in findings resembling significant aortic valve regurgitation. Rarely, the tunnel connects the aorta to the right ventricle.

With a ventricular septal defect adjacent to the aortic annulus, usually a subpulmonary ventricular septal defect, the support of the adjacent aortic cusp is weakened. The cusp tends to sag into the left ventricle, and the left-to-right shunt through the ventricular septal defect exerts force on the cusp through the defect. The cusp in the ventricular septal defect tends to narrow it, while the aortic regurgitation worsens. The findings are those of a ventricular septal defect plus aortic insufficiency. Repair of the defect may buttress the aortic cusp sufficiently to reduce the aortic regurgitation and obviate surgery on the aortic valve.

Marfan syndrome is associated with dilated sinuses of Valsalva and ascending aorta. Aortic regurgitation that may be severe can result. The echocardiographic findings are diagnostic, showing greatly dilated aortic sinuses, symmetric enlargement of the ascending aorta, and often mitral valve prolapse. The diagnosis is made by characteristic features involving a number of organ systems because of abnormalities in connective tissue caused by defective fibrillin. Establishing a diagnosis of Marfan syndrome is critical because of the potential danger of aortic dissection when the ascending aorta becomes excessively dilated (> 5 cm in diameter in adults). Serial echocardiograms are used to monitor progression of ascending aortic aneurysm formation.

Rheumatic fever is a major cause of aortic incompetence worldwide, although today this is uncommon in the United States.

Finally, infective endocarditis can occur on a malformed aortic valve. Staphylococcal endocarditis in particular can destroy the valve, leading to significant aortic regurgitation.

Management

Most patients can be treated conservatively without treatment. In those with more significant regurgitation, periodic echocardiograms to assess left ventricular function should be performed to help guide decisions about operation. Afterload reduction is used with moderate or severe aortic regurgitation to lessen the regurgitant volume. Operations that involve valve replacement are reserved for those patients with chronic regurgitation who are symptomatic and have developed left ventricular dysfunction, often indicated by progressive dilatation of the left ventricle, or those patients who have developed aortic regurgitation acutely and are in failure. Surgical repair of the valves has become more common in recent years, but because the valves do not remain competent for very long, repair is reserved for small children to allow the annulus time to grow so that eventually a larger prosthesis can be implanted.53-61

Mitral Regurgitation

The primary feature of mitral insufficiency is an apical high-pitched murmur that, if moderately loud, radiates to the left axilla and left posterior thorax. Typically, it begins with the first heart sound and may continue throughout systole (pansystolic) and so occupies both the isovolumetric contraction and ejection phases of systole. In mitral valve prolapse (discussed below), the murmur begins later in systole because of the anatomic features of the valve.

When the regurgitant volume equals or exceeds the cardiac output, the first heart sound becomes loud, and a third heart sound is heard at the apex. A low-pitched, mid-diastolic murmur is heard at the cardiac apex. Arterial pulses are normal with mild regurgitation, but with massive regurgitation manifest a small collapsing pulse, as described for a large ventricular septal defect. Large R waves are found in the left precordial leads. On chest x-ray, there may be cardiac enlargement from left ventricular dilatation and left atrial enlargement, evident as elevation of the left mainstem bronchus or, if severe, as an enlarged left atrial appendage along the upper left cardiac border.

Once the regurgitant volume is twice the cardiac output, so that left ventricular volume is 3 times normal, the degree of left ventricular dilatation is excessive. Then cardiac failure with its associated symptoms and signs appears.

The echocardiogram allows assessment of hemodynamics and anatomic features of the mitral valve. Mitral regurgitation can develop secondary to both acquired and congenital anomalies of the mitral valve that are reviewed below. Internationally, the most common cause is rheumatic fever, whereas in the United States, it is usually secondary to mitral valve prolapse (up to 5% of the population).

Mitral regurgitation can occur secondary to primary anomalies of the mitral valve, which include cleft in the anterior leaflet and double orifice. Only the echocardiogram is diagnostic of these conditions. Papillary muscle dysfunction from anomalous left coronary artery or conditions with left ventricular hypertrophy can result in mitral regurgitation. In the former, the electrocardiogram is typical; in the latter, the cause of left ventricular hypertrophy can typically be found on clinical examination, electrocardiograms, or echocardiograms. In adults, mitral regurgitation is often due to spontaneous rupture of chordae tendineae, but in children such rupture is rare and usually follows chest trauma.

In some patients, mitral regurgitation improves following medical or surgical treatment of the underlying condition (eg, left atrial myxoma, endocardial cushion defect, anomalous left coronary artery, severe aortic stenosis, idiopathic hypertrophic subaortic stenosis). In these, improvement occurs without direct treatment of the mitral valve. Mitral regurgitation secondary to neonatal asphyxia or hypoglycemia generally improves spontaneously during the first year of life, as the ischemic left ventricular myocardium recovers. Many patients require no treatment, but in those who become symptomatic or have moderate regurgitation, afterload reduction may lessen the regurgitant volume and delay valve replacement.

A cleft mitral valve may be repaired directly, but other forms of mitral regurgitation generally require valvoplasty or valve replacement. Replacement is reserved for those with symptoms or deteriorating left ventricular function when a conservative operation is not possible. Recently, transcatheter clipping of the valve leaflets has lessened the degree of regurgitation, but the role of this procedure has not been established.

Mitral Valve Prolapse

In this condition, the posterior leaflet of the mitral valve, or occasionally the anterior leaflet as well, prolapses into the left atrium. The reasons for prolapse are unknown. Mitral valve prolapse occurs in increased frequency in patients with connective tissue disorders of Marfan or Ehlers-Danlos syndromes and also with mucopolysaccharidoses, ruptured chordae (perhaps from subacute bacterial endocarditis), and certain cardiac anomalies (such as atrial septal defect) associated with reduced left ventricular volume. Because the leaflets of the mitral valve are tethered by the chordae tendineae to the left ventricular papillary muscles, the extent and duration of the prolapse depend on the left ventricular volume. Left ventricular volume is larger when the patient reclines and is smaller when the patient sits or stands. Thus, in the former state, the mitral valve prolapses less and for a shorter period of time than in the latter positions.

Mitral valve prolapse can be recognized by typical auscultatory findings that are usually diagnostic. At the apex, a late systolic crescendo murmur is heard, often initiated by a click. When the patient sits or stands, the murmur is louder and longer, and when the patient squats or reclines, it becomes softer, shorter, and later in systole. Most patients are asymptomatic, but some have chest pain or palpitations of unknown cause. There are no typical electrocardiographic or radiographic findings, but the echocardiogram, if performed, demonstrates the anatomic and hemodynamic features. There is an association with thoracic anomalies, such as pectus excavatum, scoliosis, or straight back syndrome.

Mitral valve prolapse is common in Marfan syndrome because of the elongated chordae tendineae. The resultant mitral regurgitation can become significant, causing major left atrial enlargement to such a degree that atrial fibrillation may develop. The physical findings in a patient with Marfan syndrome are generally typical and diagnostic (Chapter 181).

Pulmonary Regurgitation

The primary finding of pulmonary regurgitation is an early decrescendo diastolic murmur beginning with the pulmonary component of the second heart sound. The murmur is usually low pitched, unlike a murmur of aortic regurgitation, because of the low pulmonary artery diastolic pressure. The murmur is high pitched when pulmonary hypertension is present, as in a neonate or a patient with pulmonary vascular disease in whom pulmonary regurgitation develops.

Pulmonary regurgitation is usually well tolerated because of the low pulmonary artery diastolic pressure and shape of the right ventricle. Thus, children are asymptomatic with this condition and have a near-normal exercise tolerance. Congestive cardiac failure is uncommon unless there is pulmonary hypertension or abnormal right ventricular function, but it may appear after many years of marked regurgitation.

If the regurgitant volume exceeds twice normal, a soft pulmonary systolic ejection murmur may be heard, accompanied by widened, but variable, splitting of the second heart sound. Because of the increased anterograde flow into the pulmonary trunk and proximal pulmonary arteries, the pulmonary arterial pulse pressure is increased, and the pulmonary arteries are pulsatile, as shown by imaging techniques. On a chest x-ray, the pulmonary trunk and proximal pulmonary arteries may be dilated. With increasing volumes of blood in the right ventricle, the right ventricle dilates, leading to cardiomegaly on a chest x-ray and an rSr in the right precordial electrocardiographic leads.

The most common cause of pulmonary regurgitation is postoperatively after relief of pulmonary stenosis, either isolated or combined with a ventricular communication (most frequently tetralogy of Fallot). After either a valvotomy or a balloon valvoplasty for valvar pulmonary stenosis, the degree of regurgitation and the hemodynamic alterations are usually minimal. In patients in whom pulmonary stenosis has been relieved by a transannular patch or in whom a ventriculotomy is done for an intracardiac repair, fatigue or cardiac failure may develop, cardiomegaly is found, and the electrocardiogram shows complete right bundle-branch block. In these instances, probably the combination of the degree of pulmonary regurgitation and the altered right ventricular function results in hemodynamic dysfunction that might not have been present with a normally functioning right ventricle. These patients may develop exercise fatigue from inability of the right ventricle to increase cardiac output during exercise and eventually right heart failure.

Congenital pulmonary regurgitation is rare and may be associated with either an intact ventricular septum or a ventricular septal defect. Isolated pulmonary insufficiency with intact ventricular septum can cause cardiac failure in the immediate neonatal period because of the elevated pulmonary artery pressure normally present at this age. This elevation greatly augments regurgitation and leads to profound and sometimes fatal cardiac failure.

Management

Most patients with pulmonary regurgitation after valvoplasty, valvotomy, or transannular patch do not require treatment but should be followed periodically. If symptoms or evidence of significant decreased right ventricular function is determined by echocardiography, valve replacement should be performed. Studies are now being done to evaluate the results of inserting prosthetic pulmonary valves by catheter.

In infants with coexistent ventricular septal defect and absent pulmonary valve, an operation to close the ventricular septal defect and plicate the main pulmonary arteries should be done.

For a neonate with absent pulmonary valve and intact ventricular septum, giving nitric oxide via a ventilator may relax pulmonary arterioles and lower pulmonary vascular resistance. Once pulmonary artery pressure reaches normal levels, the symptoms disappear.62-66

Tricuspid Regurgitation

In tricuspid regurgitation, the primary finding is a pansystolic murmur along the lower left sternal border; the murmur may radiate toward the right. The murmur is usually low pitched because of the low right ventricular systolic pressures but is higher pitched if associated with a high right ventricular systolic pressure.

Because of the increased right atrial volume, the right lower cardiac border of the chest x-ray may be rounded and prominent, and the electrocardiogram shows tall and slightly broadened P waves of right atrial enlargement. If significant, jugular veins are distended, and the liver is enlarged.

Because of the increased anterograde flow, a low-pitched mid-diastolic murmur is present in the tricuspid area. Once the right ventricular volume exceeds twice normal, cardiomegaly and an rSR (lead V1) may be found.

Because of the low right ventricular systolic pressure, compliant right ventricle, and right ventricular shape, this condition is usually well tolerated and unassociated with congestive cardiac failure unless right ventricular dysfunction coexists.

Tricuspid regurgitation is common, secondary to congenital or acquired conditions associated with right ventricular dilatation, although the degree is often mild and detectable only by color Doppler interrogation of the tricuspid valve. Two particularly critical conditions causing tricuspid regurgitation can present in the neonatal period.

Transient Tricuspid Insufficiency of the Neonate

In some neonates with severe perinatal stress, marked tricuspid regurgitation may develop secondary to right ventricular myocardial ischemia. Affected neonates often have acidosis and hypoglycemia. Myocardial enzyme levels (creatine kinase MB band) are elevated. Pulmonary hypertension frequently coexists and accentuates the degree of regurgitation.

Cardiac failure may be present, accentuated by the elevated pulmonary vascular resistance and myocardial dysfunction. There are no distinguishing features other than the perinatal history and frequently ST segment and T-wave changes on an electrocardiogram. Treatment is supportive with inotropes to improve myocardial function, ventilator support to reduce oxygen consumption, and nitric oxide.

The tricuspid regurgitation generally resolves during infancy as pulmonary resistance declines and the right ventricular myocardium recovers. Usually by 6 months of age, there are no abnormal findings.

Ebstein Malformation

This congenital cardiac anomaly must be considered in the differential diagnosis of tricuspid insufficiency and is discussed above.

Secondary to Right Ventricular Dysfunction

Tricuspid regurgitation may develop secondary to right ventricular dysfunction. The 2 common situations in which this occurs in childhood are right ventricular failure and severe pulmonary stenosis. The former is found late in the postoperative course of children following atrial baffle procedures for complete transposition or right ventriculotomy (plus conduit placement), as in tetralogy of Fallot.

In those patients following atrial baffle procedures, because the right ventricle is connected to the aorta, systemic afterload reduction reduces the degree of regurgitation. Among those who have significant postoperative pulmonary regurgitation following repair of tetralogy of Fallot, repair of this problem often reduces right ventricular volume and lessens the tricuspid regurgitation. In children with severe pulmonary stenosis, tricuspid regurgitation may develop from either coexistent structural anomalies of the tricuspid valve or right ventricular dysfunction. In these patients, the regurgitation is accentuated by the elevated right ventricular systolic pressure. Relief of the pulmonary stenosis is generally sufficient to diminish the tricuspid regurgitation. Many patients with hypoplastic left heart syndrome who have undergone various stages of surgical palliation have significant tricuspid insufficiency because the right ventricle dilates under the increased afterload of the systemic circulation.

Rare causes of tricuspid regurgitation include endocarditis, which occurs on a normal valve in addicts following intravenous injection of contaminated drugs. Carcinoid disease is another rare cause. Other primary congenital anomalies of the tricuspid valve are also rare and include isolated cleft of the septal leaflet, abnormal chordae tendineae, or structural abnormalities of the leaflets.67-72

Obstructive Lesions

Obstructive congenital cardiac lesions are conveniently classified as obstructions on the left or right sides of the heart. Obstruction of flow because of a congenital abnormality may occur in any part of the pulmonary and systemic vascular systems, but the outflow tracts of each ventricle are most often affected. The obstruction may be so mild as to produce no significant hemodynamic effects or so severe as to cause total obstruction of flow. Mild or moderate obstruction is called stenosis, whereas complete obstruction is termed atresia. Atresia may occur at an atrioventricular valve, at a semilunar valve, or in the aortic arch. With atresia, blood is diverted from its normal pattern of flow and is directed through abnormal pathways to maintain systemic or pulmonary blood flow. Most of these complex lesions involve complete admixture of pulmonary and systemic venous returns and thus produce both right-to-left and left-to-right shunting; they are considered below. When the obstruction is incomplete, blood flow is largely maintained through normal pathways, and the basic anatomy is unaltered. However, to maintain a normal output through the stenosis, an unusually high pressure proximal to the obstruction is required, causing an increased pressure load proximal to the obstruction. For example, narrowing of the aorta increases left ventricular systolic pressure; with severe obstruction, left ventricular end-diastolic pressure rises. Left atrial and pulmonary venous pressures then increase, and pulmonary edema may occur. This causes pulmonary hypertension and eventually right ventricular failure, with an increase in systemic venous pressure. In association with the increased pressure, the chamber of the heart involved dilates and eventually hypertrophies in order to maintain the pressure load. If this cannot be accomplished, cardiac failure occurs, and cardiac output and arterial blood pressure fall. It is important to remember that although the foramen ovale is functionally closed soon after birth, it may allow shunting between the 2 circulations in either direction if there is an obstruction distal to it.

A general pathological effect of an obstruction is to cause hypertrophy of the chamber(s) proximal to the obstruction. This will cause electrocardiographic changes of hypertrophy of the involved chamber(s). Because hypertrophy from obstruction merely thickens the chamber wall by a few millimeters, the chest roentgenogram usually does not show an enlarged heart (unless there is also dilatation), although shape changes of the chambers are sometimes visible.

Left Heart Obstruction

Pulmonary Venous Obstruction

Obstruction to pulmonary venous return is generally associated with abnormal connection of the pulmonary veins, either below or above the diaphragm (see Total Anomalous Pulmonary Venous Connection, below), and may occur for the first time after surgical repair of these anomalous veins. Obstruction of normally connected pulmonary veins does occur occasionally as a result of external compression by a posterior mediastinal mass, fibrosis, or an intrinsic abnormality in the pulmonary veins; single or multiple pulmonary veins may be involved. Intrinsic narrowing may be caused by diffuse hypoplasia, a localized diaphragm, or narrowing of the pulmonary veins as they enter the left atrium.

Pulmonary venous pressure increases with an anatomic obstruction to pulmonary venous return. The rise in pulmonary venous pressure causes increased transudation of fluid through the capillary walls into the interstitial lung spaces, from where it passes into alveoli or lymphatics. The fluid accumulation makes the lungs stiff and is clinically apparent as respiratory distress, retractions, and rales, as well as by interference with gas exchange, particularly of carbon dioxide, leading to increasing arterial blood carbon dioxide tension. As fluid accumulates, there is lymphatic engorgement that on chest roentgenogram is associated with Kerley B lines, fluid in the major fissures, and eventually pleural effusion. In some infants in whom congenital lymphangiectasis has been diagnosed, subsequent autopsy examination has revealed pulmonary venous obstruction, usually associated with total anomalous pulmonary venous connection.

Frequently an increased pulmonary venous pressure is associated with an increased pulmonary vascular resistance. The suggested mechanisms that produce this effect include a decrease in oxygen tension to which the resistance vessels are exposed, with resultant pulmonary vascular constriction, and compression of the resistance vessels by edema fluid. Reflex vasoconstriction has been postulated but never proved. With the increase in pulmonary vascular resistance, pulmonary arterial pressure rises, causing a pressure overload on the right ventricle.

The clinical presentation includes the signs and symptoms of pulmonary edema and pulmonary hypertension. It can be to differentiate certain forms of chronic pulmonary disease from pulmonary venous obstruction.

Treatment of pulmonary venous obstruction is surgical repair. Anomalous veins are attached to the left atrium; intrinsically stenotic veins are enlarged with a patch. Recurrence of stenosis with the need for multiple surgeries is common. Newer methods in which the stenotic regions are excised and suturing of the veins is avoided by suturing the pericardium around the vein seem to reduce recurrences. Nonsurgical catheter-based treatment, including balloon dilatation, alone or with stent placement, has been used. Although immediate improvement is common, recurrence of stenosis is frequent, and therefore this therapy has limited use. Lung transplantation remains an option for those patients who have failed repeated conventional surgeries.

Obstruction Within the Left Atrium

Cor triatriatum is a membrane in the midportion of the left atrium; the membrane obstructs flow from the pulmonary veins to the mitral valve. Failure of resorption of the common pulmonary vein results in division of the left atrium into upper and lower chambers during development. The pulmonary veins drain into the proximal chamber that communicates through an obstructive opening with the distal portion of the atrium, which in turn is connected to the atrial appendage and the mitral valve. The physiological effects and clinical presentation are the same as in pulmonary venous obstruction. The diagnosis is made by echocardiography, cardiac catheterization with angiocardiography or magnetic resonance imaging. Treatment consists of surgical excision of the obstructing membrane and is curative.

An equally uncommon lesion producing obstruction within the left atrium is a supravalvar mitral ring, often associated with a parachute mitral valve, subaortic stenosis, and coarctation of the aorta (Shone syndrome). The supravalvar mitral ring is a membrane that develops in the left atrium adjacent to the mitral valve and restricts leaflet motion, causing obstruction. A tumor within the left atrium, usually a myxoma, can also produce obstruction within the left atrial chamber, and it generally mimics mitral stenosis; however, because such a tumor is often on a pedicle, the obstruction to the mitral valve orifice (and hence the clinical features) may be intermittent. Treatment of supravalvar mitral ring and myxoma is by surgical resection, which is curative.

Mitral Valve Obstruction

Outflow from the left atrium can be obstructed by either abnormalities of the mitral valve apparatus or left ventricular failure and results in increased atrial pressure. The left atrium dilates and hypertrophies. Left atrial pressure loading may be inferred clinically on hearing a well-marked fourth heart sound that suggests more forceful contraction by the hypertrophied atrium. Electrocardiographically there may be a widely notched P wave in lead II and in leads V5 and V6, and the P wave in V1 may be enlarged with a prominent negative or biphasic component suggesting left atrial enlargement. On a chest roentgenogram the typical signs of left atrial dilatation, prominent left upper heart silhouette and superiorly deviated left bronchus, may be seen. An increased pulmonary venous pressure is manifested by tachypnea, the cardinal sign of left ventricular failure.

The most severe form of mitral valve obstruction is mitral atresia, discussed below in Hypoplastic Left Heart Syndrome. Congenital mitral stenosis may be an isolated defect or may be associated with other abnormalities such as an atrial or ventricular septal defect, aortic stenosis, coarctation of the aorta, or endocardial fibroelastosis. Congenital malformations of the mitral valve may produce grossly abnormal valve cusps or a valve that appears normal but has fused commissures or else fusion of chordae tendineae below the valve ring. Parachute mitral valve, in which the chordae tendineae are all attached to a single papillary muscle, also obstructs flow at the mitral valve level. This may occur as an isolated lesion, but it is more commonly part of a complex group of left heart obstructions, known as Shone syndrome.

The congenital forms of mitral stenosis are generally severe and present in early infancy with symptoms and physical findings of pulmonary edema; if pulmonary hypertension occurs, severe congestive cardiac failure may supervene. Various degrees of mitral regurgitation may be associated with the stenosis, and there may be an apical blowing murmur. An opening snap of the mitral valve may be heard, but this is not common because the valve is very thick and immobile. Tricuspid regurgitation may occur if there is severe pulmonary hypertension with right ventricular dilatation. On the electrocardiogram, the P waves are broad and notched, suggesting left atrial enlargement, and right ventricular hypertrophy may be present. The chest roentgenogram shows only moderate enlargement of the cardiac silhouette caused by left atrial and possibly right ventricular enlargement. The pulmonary vascular markings depend on the severity of obstruction. In severe mitral stenosis in older children and adults, the increased pulmonary venous pressure dilates the veins near the lung apex (erect position), but dependent edema in the lower parts of the lungs constricts them, the reverse of the normal radiographic pattern. In infants who spend much of their time horizontal, this sign is usually absent.

The specific diagnosis may be made by echocardiography and rarely needs confirmation by cardiac catheterization and angiocardiography.

Medical treatment of severe congenital mitral stenosis with intractable heart failure in infancy and early childhood is usually unsuccessful. Surgical management, because of the marked thickening and deformity of the mitral valve, generally involves inserting a prosthetic valve; however, in older patients valve repair may be tried. The prosthetic valve has a limited effective life, and surgical replacement with a larger prosthetic valve is needed to accommodate growth. In addition, children with a prosthetic mitral valve must be given anticoagulants to prevent thrombosis of the valve. Recently dilatation of the stenotic valve with a balloon catheter has shown promise, particularly in older patients (see Chapter 499). If the left ventricle is hypoplastic, then repair of the mitral valve may not be appropriate, and a Fontan or single ventricle–type surgical repair may be needed.73-85

Left Ventricular Outflow Obstruction

Most left ventricular obstructive lesions do not occur rapidly, and compensatory myocardial hypertrophy occurs in response to the increased systolic pressure in the chamber. The increased muscle mass allows increased cardiac work to be performed with little ventricular dilatation and without greatly increased end-diastolic pressures. As an additional response to stress, increased sympathetic activity occurs and produces greater contractile force and rate of ejection, thus shortening systole and lowering end-diastolic pressure. However, with severe obstruction, even these compensatory mechanisms may fail, and the left ventricle dilates and end-diastolic pressure increases.

A further important consideration in the response of the myocardium to an increased pressure load is the ability to provide an adequate oxygen supply. The oxygen requirements of the left ventricular myocardium are related to the systolic pressure generated within the ventricle, the thickness of the wall, the diameter of the cavity, and the degree of sympathetic stimulation. The amount of oxygen supplied to the myocardium is related to the aortic diastolic pressure, the left ventricular diastolic pressure, the duration of diastole, and the oxygen-carrying capacity of blood perfusing the myocardium. Therefore, with severe obstruction, oxygen requirements are significantly increased, but the supply of oxygen may be compromised if there is left ventricular failure with an increase in ventricular end-diastolic pressure and a shortened diastolic duration because of the compensatory tachycardia. If the ventricle is both hypertrophied and dilated, the increased wall tension increases myocardial oxygen demand still further and adds to the risk of subendocardial ischemia

The left ventricular response to obstruction is manifested by left ventricular hypertrophy, inferred from a slow forceful heave of the left ventricular apex. Hypertrophy alone does not significantly enlarge the external heart dimensions, for the increased wall thickness may be only a few millimeters, but if there is associated dilatation, the left ventricular apex is displaced downward and to the left. The heart may or may not show enlargement on a roentgenogram; even if it is not enlarged, there may be a slightly more rounded left ventricular contour than typically seen. There are no specific changes in the first or second heart sounds, but a third heart sound may appear; if there is systemic hypertension, aortic closure is loud. Electrocardiography shows increased left inferior and posterior forces. The mean frontal-plane QRS axis is normal with pure left ventricular hypertrophy because an inferiorly placed ventricle with a normal sequence of depolarization does not produce the left superior axis, termed left axis deviation.

Several congenital cardiovascular malformations obstruct ejection of blood from the left ventricle. The most common of these is obstruction of the aortic valve cusps; however, the left ventricular outflow tract may be obstructed by an abnormally situated mitral valve leaflet or papillary muscle, by muscular hypertrophy of the ventricular septum, by a subvalvar fibrous ring, by a thin subvalvar membrane with a small orifice, or by supravalvar aortic narrowing. Because valvar aortic stenosis is the most common form of aortic stenosis, it is described in detail, and differences associated with other forms of left ventricular outflow tract obstruction are identified.

Valvar Aortic Stenosis

About 85% of congenitally stenotic aortic valves are bicuspid, with one small and one large cusp and an eccentric fish-mouth orifice between them. Another 14% have no obvious separation into leaflets, so that there is a thick monocusp with an eccentric orifice shaped like a teardrop. The obstruction results in part from the small orifice left by commissural fusion and in part from thickening and lack of mobility of the valve. In the neonate, some of these abnormal valves have myxomatous thickening.

Somatic development is usually normal at the time of birth. If the stenosis was severe in utero, then blood will have been diverted from the left ventricle, so that it and the ascending aorta are hypoplastic. Because of the high left ventricular pressure, there may be marked endocardial thickening (secondary endocardial fibroelastosis) that further impairs left ventricular performance. Subendothelial blood flow may be inadequate, and subendocardial ischemia may result. In moderately severe aortic stenosis exersize may cause anginal pain and S-T depression or T-wave inversion in the left ventricular electrocardiographic leads. Ischemia or ischemic damage may also be responsible for the occasional sudden death, due to ventricular fibrillation. One other symptom of severe aortic stenosis is syncope, usually following exertion or prolonged standing. Lesser degrees of stenosis cause left ventricular hypertrophy with no evidence of ischemia at rest or exercise, and the mildest stenotic lesions produce only a murmur with no left ventricular hypertrophy.

After birth, in an infant with severe aortic stenosis, if the foramen ovale is competent, left atrial pressure rises, and left ventricular output is well maintained, but at the expense of pulmonary edema. If, however, the foramen ovale is incompetent and allows a large left-to-right shunt, left atrial pressure may not rise as much, so there may be less pulmonary edema but at the expense of a lower cardiac output. In either circumstance, left ventricular dilatation may be marked, and left ventricular failure occurs. Infants with less severe aortic stenosis are generally capable of maintaining cardiac output and of developing adequate hypertrophy to overcome the obstruction.

Congenital aortic stenosis is usually progressive. As the child grows and cardiac output increases, the valve orifice may not grow to keep pace with increased cardiac output requirements; thus, the obstruction becomes more severe, and the pressure difference between the aorta and left ventricle increases. Rapid changes in the severity of aortic stenosis may occur with rapid growth spurts.

Clinical Features

Severe aortic stenosis generally presents in the immediate postnatal period. The physical findings are those of a systolic murmur of variable intensity, depending on the left ventricular output. This systolic murmur is often best heard at the middle left sternal border in infants; it can be confused with the murmur of ventricular septal defect. An early systolic ejection click is common. Peripheral perfusion and pulses depend on the degree of failure, but they are generally decreased; these infants can be misdiagnosed as having septic shock. Evidence of significant atrial left-to-right shunting with right ventricular hyperactivity is often present. Mitral regurgitation can be severe due to papillary muscle ischemia. Chest roentgenograms show marked cardiomegaly with severe pulmonary venous congestion. The electrocardiogram often shows increased right ventricular forces; increased left ventricular forces are rarely present in the neonate. An echocardiogram may show the abnormal aortic valve and usually demonstrates a dilated, poorly contractile left ventricle, sometimes with bright subendocardial echos that indicate secondary fibroelastosis.

In older children with aortic stenosis, the murmur usually draws attention to the defect. Chest or epigastric pain or syncopal episodes are generally associated with severe stenosis and are uncommon presenting symptoms. They may develop in a child known to have aortic stenosis, indicating progression in severity of the stenosis. Many of the physical findings of aortic stenosis correlate roughly with the severity of the stenosis. If there has been long-standing severe obstruction from infancy, a left precordial bulge and an apical impulse in the left anterior axillary line may be evident. In children with moderately severe stenosis, the systemic arterial pulse is usually normal. In adults, as the stenosis becomes more severe, the upstroke of the pulse is slowed, and pulse volume is decreased; this sign is uncommon in children, even those with moderately severe stenosis. The first heart sound may be normal or soft in severe stenosis. Commonly, an early systolic ejection click is heard along the left sternal border and is usually transmitted toward the apex of the heart.

A prominent apical third sound is frequently heard, and in severe stenosis a fourth sound may also be present. A loud crescendo-decrescendo systolic murmur, often grade 4 to 5 in intensity and associated with a suprasternal notch thrill, is characteristic of aortic stenosis. The murmur starts with the first sound and reaches peak intensity early in systole in mild stenosis and later in systole in more severe stenosis.

The electrocardiogram may show left ventricular hypertrophy, but this is a poor index of the severity of the stenosis. T-wave flattening or inversion and S-T segment depression in left ventricular precordial leads indicate left ventricular strain from severe aortic outflow obstruction and indicate the need for treatment. These changes may not be present at rest but may be brought out by graded exercise. The chest roentgenogram occasionally shows left ventricular enlargement, but more often the only abnormal finding is poststenotic dilatation of the ascending aorta.

It is important to realize that symptoms, physical findings, chest roentgenograms, and electrocardiograms are unreliable in predicting the severity of aortic stenosis. It is for this reason, and because sudden death may occur in children with stenosis and relatively minor physical findings, that the pressure difference between aorta and left ventricle and the hemodynamic status should be evaluated carefully by Doppler examination or cardiac catheterization.

Echocardiography with Doppler examination is essential for any child with aortic stenosis with or without symptoms, congestive heart failure, or electrocardiographic changes of left ventricular hypertrophy. If there is no evidence of myocardial ischemia at rest, an exercise test may help to determine the adequacy of myocardial perfusion. Any suggestion that the stenosis is severe should lead to referral for treatment. In most centers, cardiac catheterization is performed when there are doubts about the echocardiographic findings or the stenosis is severe enough to warrant treatment. If valvotomy is not needed, these patients should be followed at least yearly with electrocardiograms at rest and during exercise and by echocardiogram-Doppler study because of the tendency of this lesion to become more severe.

Treatment

Symptoms of chest pain or syncope warrant immediate evaluation and treatment, as does evidence of ischemia on ECG. A pressure gradient of greater than 70 mm Hg measured with echo Doppler velocity generally indicates the need for treatment in an asymptomatic patient. This most often correlates with a valve area of less than 0.65 cm2/m2 body surface area, normal being greater than 2 cm2/m2. Treatment historically has been surgical valvotomy, but balloon valvoplasty has become the treatment of choice (see Chapter 499). Both forms of valvotomy are only palliative; but palliation is lifesaving and may produce a good functional result that lasts for many years. However, there is a high incidence of recurrence of stenosis, often associated with calcification, and 40% of patients require repeat treatment within 10 years. Most patients with severe stenosis will eventually require surgical treatment. If possible, surgical treatment should be deferred until the patient is fully grown to avoid repeat surgical procedures. Surgical options include moving the pulmonary valve ring with the intact valve into the aortic annulus, implanting the coronary arteries into the new aortic root, and placing a homograft aortic valve into the right ventricular outflow tract (Ross procedure), or doing an aortic homograft (new pulmonary valve) that will usually require replacement every 10- to 15 years.

Bicuspid Aortic Valve

Bicuspid aortic valve is present in 1% to 2% of the population. There is an asymmetric orifice, and the valve may not open fully in systole, but there need not be any obstruction to left ventricular ejection. Bicuspid valves are found in 50% of patients with coarctation of the aorta but more often are isolated anomalies. Sometimes they are associated with a grade 1 to 2/6 systolic ejection murmur and click at the right upper sternal border, but often they are not clinically apparent. The diagnosis is best made by 2-dimensional echocardiography.

The importance of bicuspid aortic valves is that they may produce aortic stenosis in later life; middle-aged adults with calcific aortic stenosis usually have congenitally bicuspid aortic valves. The likelihood of late development of calcific aortic stenosis or less often aortic regurgitation is high. Occasionally, bicuspid aortic valves are the seat of infective endocarditis; thus, if bicuspid aortic valves are diagnosed, prophylaxis against infective endocarditis should be given.

Poststenotic dilatation of the aorta is common, and the aortic wall is often abnormal, sometimes showing cystic medial necrosis. Dissection of the ascending aorta may occur but is very rare under 40 years of age.

Discrete Subvalvar Aortic Stenosis

Subvalvar aortic stenosis may be caused by either a thin membranous diaphragm or a thick fibromuscular obstruction. The aortic valve may be thickened and distorted by the high-velocity jet stream passing through the subaortic obstruction and may be regurgitant. The clinical features are similar to those observed with valvar aortic stenosis, and there are no reliable clinical criteria to differentiate valvar from subvalvar obstruction. The 2-dimensional echocardiogram may be used to define more accurately the type, thickness, and site of obstruction present. In addition to the subaortic obstruction, there may be hypoplasia of the aortic annulus.

Subaortic stenosis may be isolated or may be associated with Shone syndrome, ventricular septal defect, or other forms of congenital heart disease. Unlike most other forms of congenital heart disease, subaortic stenosis may not be present at birth but develops later. It may increase in severity with time.

Differentiation between valvar and subvalvar aortic stenosis by echocardiography or occasionally by cardiac catheterization and angiocardiography is important because a subvalvar diaphragm is readily removed at surgery with good results and because even mild subvalvar obstruction may cause progressive aortic valve damage and regurgitation. Unfortunately, recurrence of obstruction is common. Some children may have subvalvar obstruction from an abnormally placed papillary muscle and displaced mitral valve. This is much more difficult to alleviate surgically, and it may be complicated by mitral regurgitation.

Diffuse Subaortic Stenosis

Diffuse subaortic left ventricular outflow stenosis may be associated with any cause of diffuse hypertrophy of the left ventricle. It occurs with valvar aortic stenosis and with certain types of cardiomyopathy, such as glycogen storage disease. Infants born to diabetic mothers have a high incidence of a mild form of diffuse cardiomyopathy, although a few may have severe asymmetric septal hypertrophy. The abnormalities are temporary and generally resolve within several months. Some children with Noonan syndrome have a specific form of eccentric subaortic stenosis. Tumors, such as rhabdomyomas, may also cause outflow obstruction. In premature infants with chronic lung disease treated with steroids, a diffuse symmetric hypertrophy may develop. This regresses spontaneously once steroid treatment is discontinued.

The most common form of diffuse subaortic stenosis is idiopathic. This entity has been called idiopathic hypertrophic subaortic stenosis (IHSS), hypertrophic obstructive cardiomyopathy (HOCM), hypertrophic cardiomyopathy (HCM), or asymmetric septal hypertrophy (ASH). The disease is transmitted as a Mendelian dominant with variable expression and is usually seen in more than one member of a family. In some families there is a tendency to ventricular arrhythmias and less severe outflow tract obstruction, whereas in others there is severe obstruction. About 50% of patients have mutations that map to the myosin heavy chain on chromosome 14; many different mutations are now known. Other mutations affect cardiac troponin T and α-tropomyosin. Linkage studies have also suggested mutations on chromosomes 1, 11, and 15.

Many of the physical findings are similar to those in valvar aortic stenosis, but certain features usually distinguish them. A double or triple apical impulse, described as a precordial ripple, is often seen or palpated. The first heart sound may be normal or soft; systolic clicks are rarely heard. The suprasternal notch thrill is absent. A delayed-onset crescendo-decrescendo systolic murmur, usually of grade 2 to 4/6 intensity, may be heard best at the middle left to upper right sternal border, and a systolic thrill may be palpable over the precordium. If the patient squats, thereby increasing venous return and peripheral vascular resistance, the murmur decreases in intensity as a result of left ventricular dilatation. All these maneuvers tend to produce opposite effects in valvar aortic stenosis. The chest roentgenogram shows left ventricular enlargement without dilatation of the ascending aorta. The electrocardiogram is variable, but with severe or moderately severe hypertrophy, there are markedly increased left ventricular forces often associated with S-T segment depression and T-wave flattening or inversion in the left precordial leads. Deep Q waves in the left precordial leads indicative of septal hypertrophy are more evident than in valvar aortic stenosis.

The 2-dimensional echocardiogram has been of great help in diagnosing this lesion. It demonstrates the asymmetric septal hypertrophy, and during systole it usually shows anterior movement of the mitral valve (SAM), which touches the septum and in part causes the outflow tract obstruction. SAM is not always demonstrated but usually can be provoked by maneuvers that precipitate outflow obstruction, such as amyl nitrite inhalation or the Valsalva maneuver.

Children with this disease are more likely to die from arrhythmias than from obstruction and heart failure. The results of treatment of this lesion are variable. Some children respond fairly well to β-adrenergic-receptor blockers; however, this is generally of only temporary benefit. Calcium antagonists are useful, particularly when the major problem is decreased diastolic ventricular distensibility. Inotropes must be avoided. Surgical excision of the hypertrophied muscle has produced marked improvement in some children. Atrioventricular sequential pacing in conjunction with β-adrenergic blocker therapy has been used successfully. Because the ventricle is stimulated from the right side of the septum, there is asynchronous contraction of the left ventricle, the septum relaxes before the rest of the ventricle contracts, and outflow tract obstruction is reduced. Controlled comparisons in adult patients suggest that surgical resection may be more effective than pacing at gradient reduction. In the late 1990s a catheter-based treatment was developed consisting of intentional infarction of the hypertrophied septum by instilling alcohol solution into a septal perforating coronary artery. This has been used successfully in adults to reduce the outflow obstruction; however, long-term follow-up is not available, and the technique has not been applied to children. Unfortunately, death from arrhythmia can occur even without any obstruction, and some patients require an implantable pacemaker-defibrillator.

Supravalvar Aortic Stenosis

Supravalvar aortic stenosis is a localized or diffuse narrowing just above the level of the coronary arteries and the superior annular margin of the sinuses of Valsalva. The coronary arteries usually arise proximal to the obstruction and are often tortuous, with thickened medial and intimal layers. Coronary perfusion may be compromised by involvement of the coronary ostia in fibrous tissue. Although supravalvar aortic stenosis may occur as an isolated lesion, it is often associated with Williams syndrome, also known as idiopathic infantile hypercalcemia (see Table 176-1). On auscultation the aortic closure sound is frequently accentuated; an ejection click is unusual, and the systolic murmur is best heard at the base and toward the neck. If peripheral pulmonic stenosis is associated, a continuous murmur may be heard laterally in the chest. Characteristically, blood pressure is about 15 mmHg higher in the right than the left arm. The chest roentgenogram does not show poststenotic dilatation of the ascending aorta. The electrocardiogram shows left ventricular hypertrophy as well as T-wave inversion in left chest leads if there is severe stenosis. Magnetic resonance imaging and echocardiography demonstrate the supravalvar narrowing, and Doppler study can assess the pressure gradient. Cardiac catheterization and angiography are done to confirm the severity of the supravalvar obstruction and associated peripheral pulmonic stenosis. If obstruction is severe, the diffuse supravalvar narrowing can be relieved surgically with excellent long-term results. If severe peripheral pulmonary artery stenosis is associated with the supravalvar obstruction, cardiac catheterization with balloon dilatation of the branch pulmonary stenoses is often performed before surgical repair. However, unlike most other stenoses, peripheral pulmonary artery stenoses in Williams syndrome often decrease in severity spontaneously.

Aortic Obstructions

Obstructive lesions of the aorta may be subdivided into diffuse narrowing (hypoplasia) or interruption of a portion of the aortic arch, discrete narrowing (thoracic coarctation) closely related to the attachment of the ductus arteriosus with the aorta, pseudocoarctation, and abdominal coarctation. The discrete thoracic coarctation is the most common lesion and is usually associated with a normally developed aortic arch.

Hypoplasia or Interruption

In normal fetal life, the aortic isthmus (the portion of aorta between the origin of the left subclavian artery and the ductus attachment) conducts only about 10% to 12% of the combined output of both the left and right ventricles. This probably explains why in healthy full-term infants the diameter of the aortic isthmus is about three-fourths that of the descending aorta; this difference usually disappears by about 6 months of age.

Pathologic hypoplasia of the aortic arch is noted most commonly in the aortic isthmus but may occur in other parts of the aortic arch. The most severe form of this lesion is complete interruption of the aortic arch. With rare exceptions, infants with aortic arch interruption or hypoplasia have associated major congenital cardiac defects, such as a large ventricular septal defect, double-outlet right ventricle, Taussig-Bing anomaly, tricuspid atresia with aortopulmonary transposition, truncus arteriosus, or endocardial cushion defect. During the newborn period, the ductus arteriosus is invariably patent. The reason for these associations is that aortic outflow obstruction associated with these intracardiac lesions may divert flow during fetal life, with a consequent reduction in the growth of the aortic arch. The clinical course of infants with these lesions is dictated by the intracardiac lesions (usually a ventricular septal defect with or without other complicating defects), by the magnitude of right-to-left flow across the ductus arteriosus, and by the degree of obstruction of the aorta.

With complete interruption, descending aortic blood flow is provided only by right-to-left flow through the ductus arteriosus. In hypoplasia of the arch, some of the descending aortic blood flow will pass through the aortic arch, the amount depending on the severity of the obstruction and the ability of the left ventricle to overcome the increased afterload. Because there is generally a significant left-to-right shunt across a ventricular septal defect, the increased pulmonary blood flow and pressure usually delay the normal postnatal fall in pulmonary vascular resistance. The elevated pulmonary vascular resistance promotes right-to-left shunting into the descending aorta through the patent ductus arteriosus and maintains lower body blood flow. Initially, while the ductus arteriosus is dilated, there may be no arterial blood pressure difference between the upper and lower body. There may be cyanosis of the toes and feet with normal color of the fingers and hands because of the right-to-left shunt at the ductus arteriosus level. However, with progressive constriction of the ductus arteriosus, the lower body arterial blood pressure falls, and its pulse pressure narrows. The progressive fall in pulmonary vascular resistance after birth further interferes with the flow of blood across the ductus arteriosus because flow will preferentially go through the pulmonary circulation rather than to the lower body. Left ventricular myocardial performance, already affected by the increased afterload, is further stressed by this volume load so that there may be severe left ventricular failure. The time course of these changes varies. As perfusion to the lower body further decreases, metabolic acidemia develops, and there may be oliguria or anuria related to inadequate renal blood flow.

In many infants the clinical presentation of these lesions is that of a large left-to-right intracardiac shunt with left-sided failure. In some of these the hypoplasia is not severe, and the arch anomaly is only of secondary importance, but in others the arch may be severely hypoplastic or even interrupted. Two-dimensional echocardiography defines clearly the intracardiac abnormalities associated with aortic arch interruption. Clear definition of the arch itself, however, is not always possible with echocardiography alone and may require cardiac catheterization with angiography.

Infants with aortic arch narrowing and an associated intracardiac lesion may respond to medical management, including digitalis and particularly diuretics. Prostaglandin E1 infusions have been extremely beneficial. After dilatation of the ductus arteriosus, lower body perfusion is often restored, renal function returns, and the infants clear acidemia. This temporizing measure then allows stabilization before surgery. Surgical repair should be done, even in premature infants, if the narrowing is severe or the arch is interrupted. At the time of correction of the aortic arch anomaly, surgical measures to correct or palliate the intracardiac lesion may be necessary.

Localized Juxtaductal Coarctation of Aorta

Several terms, such as postductal or adult-type coarctation, have been applied to this lesion. However, localized narrowing of the aorta (coarctation of the aorta) is always closely related to the insertion of the ductus arteriosus into the aorta; in fact, the posterolateral shelf that forms the localized narrowing is generally directly opposite the ductus arteriosus. For this reason, the term juxtaductal aortic coarctation is more appropriate. With closure of the ductus arteriosus and growth of the child, the usual concentric obstruction seen in older children and young adults develops. Unlike hypoplastic aortic arches, major intracardiac anomalies are not commonly found with isolated coarctation of the aorta; however, there is a high association of this lesion with Turner syndrome and with bicuspid aortic valve. Other associated abnormalities include aberrant origins of the subclavian arteries, ventricular septal defect, persistent patency of ductus arteriosus, and the group of defects associated with parachute mitral valve.

Because the ductus arteriosus is wide during fetal life, localized juxtaductal coarctation is unlikely to produce significant alteration in the distribution of blood flow during fetal life, and fetal development is normal. After birth, the ductus arteriosus constricts at its pulmonary artery end first, so that although the ductus is functionally closed, an aortic ampulla of the ductus arteriosus persists for several days to several months. There is generally a progressive reduction in the size of the ampulla as the ductus arteriosus constricts toward its aortic end. If there is a juxtaductal aortic coarctation directly opposite the aortic end of the ductus arteriosus, and the aortic ampulla remains moderately large, the posterolateral shelf does not impede flow from the ascending aorta to the descending aorta, so there will be no clinical evidence of the coarctation. However, as the aortic end of the ductus arteriosus constricts, blood flow becomes obstructed; obstruction is facilitated by constriction of an extension of ductus smooth muscle that forms a sling around the posterior shelf. If the posterolateral shelf is large, and obstruction develops rapidly, a sudden increase in afterload to the left ventricle causes left ventricular failure.

Clinical Features

The clinical presentation is often similar to that of severe aortic stenosis in the neonatal period and mimics the circulatory collapse associated with overwhelming sepsis. Significant left-to-right atrial shunting may occur through a stretched foramen ovale, and when there is severe left ventricular failure, all pulses may be weak. However, with improvement in left ventricular function, a significant pressure difference develops between the arms and the legs. Because there has been no obstruction during fetal life and failure has occurred rapidly, collateral circulation is not usually well developed in the newborn. Specific murmurs are not a feature of this lesion in infancy; however, if the ductus arteriosus is still patent, a continuous murmur may be heard at the upper left sternal border. As with aortic stenosis in infancy, the electrocardiogram typically shows right axis deviation and right ventricular hypertrophy. The chest roentgenogram shows marked generalized cardiomegaly with pulmonary venous congestion secondary to left ventricular failure. Two-dimensional echocardiography can often define the anatomy of the coarctation and, together with evaluation of the Doppler velocity signals in both the ascending and descending aorta, can assess the severity of the obstruction. If the anatomy is not clarified by echocardiography, then aortography should be done in an infant and magnetic resonance imaging (MRI) in the older child. In general, infants who have rapidly developed severe congestive failure from a coarctation in the neonatal period respond poorly to medical treatment, and surgical excision of the coarctation should be performed as soon as the patient is stable. If left ventricular function is severely depressed, inotropic support should be given. Infusion of PGE1 has been of great benefit in many of these infants in preparation for surgery, as it may relax the ductus arteriosus muscle, permitting blood to flow around the constricting shelf and relieve the acute aortic obstruction.

If the aortic shelf is not prominent, or the ampulla of the ductus arteriosus occludes gradually, aortic obstruction develops slowly over several weeks or months. Rapid left ventricular failure is less likely because compensatory mechanisms such as myocardial hypertrophy and development of collateral circulation have time to occur. Collateral anastomoses generally involve the periscapular, intercostal, transverse cervical, and internal mammary arteries. If there are large collateral vessels, only minor pressure differences may be apparent between the ascending and descending aorta at rest; larger differences may be brought out by exercise. Cardiac failure may appear at 3 to 6 months as the coarctation becomes more severe. However, if failure does not occur by 6 months of age, it is rare until adult life. In older children the presenting symptoms may be headaches related to hypertension in the ascending aorta or to intermittent claudication due to decreased blood flow to the legs during exercise. Cerebrovascular accidents associated with hypertension are rare before the age of 7 years and may be associated with rupture of berry aneurysms. Hypertension above and below the coarctation has been described, but the mechanism is unclear. Intimal thickening of the coronary arteries may occur. Infective endocarditis is also common with coarctation and usually involves the aortic wall in the dilated poststenotic segment, but it may occur on the bicuspid aortic valve.

The clinical findings in a child with coarctation of the aorta include easily palpable collateral arteries above the clavicle and over the lateral and inferior scapular margins. The arm pulses are strong, but femoral pulses are decreased and delayed relative to the arm pulses. Because there is a high association of abnormality of one of the subclavian arteries, palpation of both subclavian arteries as well as carotid arteries should be routine. An aberrant right subclavian artery arising below the coarctation gives a low blood pressure in the right arm; the left subclavian artery arises normally but may be hypoplastic, so that left arm pressures also may be low. Blood pressure measurements in the arm and leg confirm the palpated differences. Depending on the severity of the coarctation, the heart may or may not be enlarged, and an increased left ventricular impulse palpable. The heart sounds are generally normal; however, with hypertension or an associated bicuspid aortic valve, an ejection systolic click and a third heart sound may be heard. Soft high-frequency continuous murmurs are often audible over the large collateral vessels. A short, soft ejection systolic murmur may be heard at the upper sternal area or posteriorly to the left of the spine.

The chest roentgenogram has several classic features. Cardiac enlargement and left ventricular enlargement depend on the severity of the stenosis. The ascending aorta is often dilated and displaces the superior vena cava to the right. On the left border of the aortic arch and descending aortic shadow, the area of poststenotic dilatation below the coarctation and the dilated aortic segment just above the coarctation may be seen as the “3” sign. Notching of the lower margin of the ribs at about the junction of the middle and medial thirds, caused by erosion of the bone by large intercostal arteries, may be seen after 1 year of age in half the patients. The electrocardiogram demonstrates left ventricular hypertrophy from the obstruction. Older children may have S-T depression and T-wave flattening or inversion in left chest leads, but these changes are uncommon. Two-dimensional echocardiography and color Doppler flow mapping are valuable in assessing the anatomy of the coarctation and the adjacent aorta and vessels; Doppler evaluation can estimate the pressure difference across the coarctation but usually exaggerates the severity as compared to upper to lower extremity blood pressure measurements. Magnetic resonance imaging can accurately define the anatomy and should be performed if the echocardiogram is unclear.

Treatment

If the coarctation is not treated, there may be persistent hypertension, rupture of a berry aneurysm of the circle of Willis, congestive heart failure, infective endocarditis, hypertensive encephalopathy, or rupture of the aorta; the latter has been reported only in adults. For these reasons, treatment is recommended at the time of diagnosis. Surgery remains the treatment of choice in infants and young children. Excision with direct anastomosis is the surgical technique of choice whenever possible; however, widening of the aorta with a patch or part of the subclavian artery to reduce the chances of recoarctation is sometimes necessary. Some surgeons mobilize the descending aorta and then pull it up to anastomose with the underside of the arch that has been opened. This method not only eliminates the coarctation but also repairs a hypoplastic arch at the same time. Recurrent obstruction is uncommon after this procedure. Surgery has become very safe and effective, even for neonates. Recoarctation is more common if surgery is done before 2 years of age; however, its incidence is decreasing with improved surgical techniques. There is evidence that the earlier the repair, the less likely there is to be persistent “essential” hypertension that sometimes follows coarctation surgery. Balloon angioplasty for older children and angioplasty with stent placement for adolescents and adults are excellent less-invasive therapeutic alternatives to surgery. This treatment requires minimal hospitalization with return to full activities within 2 days. Balloon angioplasty of both native (unoperated) coarctation and postoperative recoarctation is effective in 80% of patients and has become the treatment of choice for all recoarctation patients. Angioplasty with stent placement is effective in over 95% of patients but has been reserved for older children and adults because of the limitations of stent size on vessel growth.

Postcoarctectomy Syndrome

Fever, abdominal pain of varying degree, abdominal distension, nausea, and vomiting may commence 1 to 3 days after surgical repair of aortic coarctation and last for several days. Systemic hypertension is always present, and renin levels are very high. In the most severe forms, infarction of segments of bowel has occurred, but in most children the syndrome is mild. This complication may be secondary to arteritis in thin mesenteric and renal arteries suddenly perfused with pulsatile flow at pressures higher than those to which they have previously been exposed. The mainstay of treatment is to lower blood pressure with antihypertensive agents. Other therapy includes fluid and electrolyte maintenance and, if necessary, abdominal decompression by nasogastric suction. Rarely, resection of an infarcted area of bowel becomes necessary.

Pseudocoarctation

Increased length of the aortic arch occurs occasionally and is probably due to retention of the third rather than the fourth cervical arch. The high arch position causes kinking of the descending thoracic aorta. Murmurs caused by turbulent flow across the arch, as well as minor pressure differences between the arms and the legs, may lead one to suspect a true coarctation of the aorta. The diagnosis is made by either cardiac catheterization with angiocardiography or magnetic resonance imaging; the distal portion of the aortic arch is generally angled anteriorly, and there is no posterolateral shelf. Usually, no specific treatment is required, although rarely aortic dissection has been reported in adults.

Abdominal Coarctation

Obstruction of the lower thoracic or abdominal aorta by an intrinsic narrowing (middle aortic syndrome) is considerably less common than the usual form of coarctation of the aorta. Rather than the short segment of constriction seen in juxtaductal coarctation, a long narrow segment is usually present, and one or several major branch arteries of the abdominal aorta are usually involved. The lesions may be congenital or due to some inflammatory change as seen in giant cell arteritis or Takayasu’s syndrome. The diagnosis is generally suspected when there is a difference between the upper- and lower-limb pulse volumes and arterial blood pressures without any indication of thoracic collateral arterial circulation or a murmur in the chest. A systolic or continuous murmur is frequently heard over the abdomen and is best heard posteriorly. The diagnosis is confirmed by 2-dimensional echocardiography with Doppler or cardiac catheterization and angiocardiography. Treatment involves surgical removal of the obstructed segment, which may be difficult because arterial branches to vital organs may be involved in the coarcted segment. If the area is not adjacent to major abdominal aortic branches, angioplasty with stent placement can be effective in the older patient.

Right Heart Obstruction

Right heart obstruction can occur in the pulmonary capillary bed, pulmonary arteries, pulmonary valve, right ventricular outflow tract (RVOT), tricuspid valve, and systemic veins. The responses of the right ventricle to an increased afterload are similar to those described for the left ventricle. Right ventricular hypertrophy produces a forceful slow lift felt best along the left sternal border and behind the sternum. If there is pulmonary hypertension, the pulmonary artery may be felt in systole in the third interspace at the left sternal border, the pulmonic component of the second heart sound is accentuated, and there may be an ejection systolic click at the base. The ventricle appears enlarged on roentgenogram only if dilated; even if the heart is not enlarged, the apex may be tipped up. If there is pulmonary hypertension, the main pulmonary artery may be enlarged. The electrocardiogram shows right axis deviation, tall R waves, or a qR complex in the right precordial leads, and there may be upright T waves at an age when they should be inverted or deep inversion of the right precordial T waves, described as a strain pattern.

When right atrial pressure rises, systemic venous return is obstructed, and systemic venous pressure rises. Should the systemic venous pressure be elevated, characteristic enlargement of liver and spleen and distention of the jugular veins occur. Peripheral edema of the soft tissues is a late finding, very uncommon in younger children.

Right atrial pressure elevation is usually the result of right ventricular failure. Right ventricular pressure elevation is frequently the result of pulmonary hypertension caused by a raised pulmonary venous pressure, which in turn follows left ventricular failure. Because left ventricular pressure overload, as in coarctation of the aorta, can cause a right ventricular pressure overload via a raised pulmonary venous pressure and vascular resistance, it is possible for the clinical picture of left heart obstruction to be dominated by the right ventricular signs.

Systemic Venous Obstruction

Obstruction to superior or inferior vena caval return may result from an extrinsic lesion such as a mediastinal mass or an intrinsic lesion such as thrombosis, or it may occur secondarily to intracardiac surgical procedures such as an atrial baffle procedure for aortopulmonary transposition. Acute obstruction may present with venous distension and edema of that portion of the body drained by the obstructed vein. Peripheral organs, particularly the liver and spleen, become congested and enlarged, and peripheral edema may result. Increased systemic venous pressure in the intestine may result in bowel edema and, eventually, ascites leading to poor food absorption, nausea, vomiting, and abdominal pain. However, collateral venous channels generally form rapidly, and these signs soon diminish. Venous collateral channels may be evident superficially. If symptoms persist, treatment by either surgical patch or balloon angioplasty with stent placement can be effective. Congenital interruption of the inferior vena cava occurs commonly with cardiac and visceral malposition; polysplenia is commonly associated. Venous drainage takes place through an enlarged azygous system, and there is usually no venous obstruction.

Obstruction in the Right Atrium

A tumor in the right atrium, generally a myxoma but occasionally an extension of a Wilms tumor or a hepatic tumor, may obstruct venous return. The clinical presentation usually mimics that of tricuspid stenosis, with intermittent obstruction when there is a myxoma. Right atrial myxomas are far less common than those in the left atrium. Thrombus formation in the right atrium may also produce venous obstruction; this is rare in children but may complicate indwelling caval or atrial catheters.

Tricuspid Valve Obstruction

The most severe form of tricuspid valve obstruction is tricuspid atresia (see Tricuspid Atresia below). Isolated congenital tricuspid stenosis is rare, and more often underdevelopment of the tricuspid valve and its annulus is associated with underdevelopment of the whole right ventricle. Underdevelopment of the right ventricle (hypoplastic right ventricle) is usually associated with either severe pulmonic stenosis or pulmonary atresia. Whether or not the ventricular septum is intact, a hypoplastic right ventricle generally presents in infancy with severe cyanosis as a result of right-to-left shunting at the atrial level.

If the interatrial septum is intact, the physical findings of tricuspid stenosis include those of venous obstruction. On auscultation there is usually a mid-diastolic rumbling murmur at the lower left sternal border as well as a prominent third sound, and in severe stenosis there is an audible fourth sound. The electrocardiogram may show tall peaked P waves indicative of right atrial enlargement, and the latter may be seen also on the chest roentgenogram.

Treatment of tricuspid stenosis often depends on the associated right heart abnormalities. Isolated valve stenosis can be repaired surgically with an annuloplasty. Associated right ventricular hypoplasia may require a palliative approach with placement of a Glenn shunt (SVC to RPA), thereby requiring the small RV to pump only the lower body blood flow.

Right Ventricular Outflow Obstruction

As with left ventricular outflow obstruction, right ventricular outflow obstruction may occur at the level of the pulmonic valve or above or below the valve leaflets. Valvar pulmonic stenosis is the most common form of right ventricular outflow obstruction. Complete obstruction, pulmonary atresia, is discussed below in Pulmonary Atresia.

Valvar Pulmonic Stenosis

In valvar pulmonic stenosis, the valve annulus is usually normally formed, but there are abnormalities of the valve leaflets. In less severe forms there are 3 normally formed cusps, but the raphae are partly fused, so that the leaflet movement is restricted. In more severe forms, there is less clear separation of the cusps, which are thickened to varying degrees and form a dome in systole. Right ventricular hypertrophy occurs in response to the valve obstruction, with significant infundibular (subvalvar) stenosis developing in more severe forms of valvar pulmonic stenosis; this tends to be progressive, producing a secondary outflow obstruction. With the more severe forms of valvar pulmonic stenosis, the valve annulus and even the entire main and major branch pulmonary arteries may be underdeveloped (hypoplastic). In children with Noonan syndrome, there is a high incidence of valvar pulmonic stenosis with thick myxomatous cusps.

Somatic development is usually normal at the time of birth in infants with pulmonic stenosis. Although the right ventricle is normally the dominant ventricle in the fetus and ejects 55% to 65% of the combined ventricular output, total fetal cardiac output is probably normal in the face of right ventricular outflow obstruction. Systemic venous return is probably diverted across the foramen ovale and ejected by the left ventricle, which assumes dominance. The wider-than-normal ascending aorta and aortic isthmus found in infants with severe pulmonic stenosis or pulmonary atresia supports this thesis.

With valvar pulmonic stenosis, development of the right ventricle and tricuspid valve in the fetus probably depends on the stage of gestation at which the stenosis occurs. If stenosis develops early in gestation, venous return is likely to be diverted across the foramen ovale, with subsequent underdevelopment of the right ventricle and the tricuspid valve and even eventual development of pulmonary atresia. However, if the stenosis occurs later, right ventricular development is more likely to be normal.

Clinical Features

Severe pulmonic stenosis presents in the immediate postnatal period and resembles pulmonary atresia with severe cyanosis and cardiac collapse as the ductus closes. In moderately severe pulmonic stenosis during infancy, mild cyanosis may be present if the foramen ovale remains patent. However, if the foramen ovale becomes sealed, the cyanosis disappears. Right ventricular failure may become evident after about 6 months, but if it does not occur at that time it is generally delayed until adulthood. Right ventricular failure will be evidenced by rapid onset of hepatomegaly, prominent pulsatile neck veins (large a waves), and a low-output state.

Most children have mild or moderate pulmonic stenosis, are asymptomatic, and are detected because of a murmur. Many of the physical findings of pulmonic stenosis correlate roughly with the severity of the stenosis. When right ventricular enlargement is produced, a fairly diffuse forceful parasternal impulse along the lower left border of the sternum may be palpable. A systolic thrill is generally palpable at the upper left sternal border. The first heart sound is usually normal but may be accentuated. A systolic ejection click is often heard along the entire left sternal border and is softer in patients with severe stenosis.

The murmur of pulmonic stenosis is an ejection systolic murmur of the crescendo-decrescendo type best heard at the upper left sternal border, with radiation to the left infraclavicular area. The frequency of the murmur correlates with the severity of stenosis, with higher frequencies heard with severe stenosis and low to medium frequencies heard with mild stenosis. During the Valsalva maneuver, as intrathoracic pressure is increased and systemic venous return and right ventricular stroke volume are reduced, the murmur of pulmonic stenosis decreases immediately unless there is congestive heart failure or severe infundibular hypertrophy.

The electrocardiogram shows right atrial hypertrophy with peaked P waves. There will also be right ventricular hypertrophy and right axis deviation, the degree depending on the severity of the stenosis. The right precordial leads show tall R waves, and with severe stenosis, they may also show T-wave inversion and S-T segment depression.

The chest roentgenogram shows right ventricular prominence with an upturned apex. The magnitude of enlargement depends on the severity of the stenosis and subsequent development of right ventricular hypertrophy. The main and left pulmonary arteries are prominent because of poststenotic dilatation. The pulmonary vascular markings are generally normal but may be slightly diminished. Valve cusp thickening, annular narrowing, right ventricular free wall thickening, and pulmonary arterial enlargement are seen on 2-dimensional echocardiography. Doppler examination reliably indicates the severity of the obstruction.

Treatment

Some children with moderate stenosis show little or no change in right ventricular systolic pressure over many years, indicating that the valve orifice has enlarged with growth. However, other children have a marked increase in right ventricular systolic pressure, suggesting either inadequate growth of the pulmonic valve orifice, development of infundibular stenosis, or both. If this should occur, right ventricular end-diastolic pressure eventually rises, and right heart failure may develop. In general, mild stenosis over 2 years of age indicates the ability of the valve orifice to grow to keep pace with the increase in stroke volume. These children are unlikely to get more severe stenosis. However, in a child seen early in infancy, the growth potential of the valve is unknown, and a mild stenosis at 3 months may occasionally become a severe stenosis by a year of age. Therefore follow-up in infancy needs to be more frequent than in older children.

Mild valvar pulmonic stenosis with a small increase in right ventricular systolic pressure may not affect right ventricular output or the right ventricular myocardium significantly. In many instances, with growth of the child, there is little or no increase in right ventricular systolic pressure, and minimal right ventricular hypertrophy may occur. The long-term outcome for mild RV pressure elevation is excellent, with minimal impact on cardiac function until late adult years, if ever.

Children with severe stenosis (right ventricular systolic pressure greater than systemic) should undergo immediate pulmonary balloon valvoplasty or, if this cannot be done, surgical valvotomy. The majority of children with severe valvar pulmonic stenosis also have infundibular hypertrophy; however, this regresses once the valvar stenosis is relieved. All symptomatic patients with exercise intolerance or fatigue and those with significant right ventricular hypertrophy should be treated, even if the measured gradient is relatively mild. Without symptoms or hypertrophy, a right ventricular systolic pressure of over 50 mmHg in children warrants treatment because over a prolonged period such pressure elevation may lead to myocardial fibrosis. Balloon valvoplasty done at cardiac catheterization is the treatment of choice in most patients, even infants; it can be performed as an outpatient procedure using sedation alone. The relief of obstruction is excellent, on average 60%, with minimal short- or long-term complications (see Chapter 499).

Subvalvar Pulmonic Stenosis

Isolated diffuse infundibular pulmonic stenosis with a normal pulmonic valve is rare. It is more likely to be associated with a ventricular septal defect. The most common type is tetralogy of Fallot, where the aorta overides a large outlet VSD and the right ventricular outflow tract is displaced medially, causing subvalvar pulmonic obstruction (see Tetralogy of Fallot below). Double-chambered right ventricle, also quite common, is caused by large aberrant muscular bands that divide the right ventricular cavity into 2 separate chambers and obstruct flow through the subpulmonic infundibular area. This anomaly is usually but not always associated with a ventricular septal defect, is often progressive, and should be treated if significant obstruction is present or there is evidence of right ventricular hypertrophy. Treatment by surgical resection of the aberrant muscle bundles with closure of the ventricular septal defect is usually curative.

Diffuse interventricular septal hypertrophy secondary to marked left ventricular hypertrophy may bulge into the right ventricle or outflow tract and thereby produce obstruction (Bernheim effect). Myocardial tumors, particularly those involving the interventricular septum, may also produce right ventricular outflow obstruction.

The clinical features of these lesions are similar to those of valvar pulmonic stenosis. An ejection click is less commonly heard, however, and poststenotic dilatation of the pulmonary artery is less prominent or absent. The systolic murmur is usually maximal at the third or fourth interspace along the left sternal border. These findings lead one to suspect subvalvar stenosis, and the diagnosis can be confirmed by echocardiography. If the anatomy or the degree of obstruction is not well defined by echocardiography, then cardiac catheterization or MRI is needed before surgical repair can be done.

Supravalvar Pulmonic Stenosis

Stenosis of the major pulmonary arteries may occur anywhere along the entire length of the pulmonary arterial tree. Obstruction may be single or multiple and may be by a diaphragm, localized narrowing, or more diffuse constrictions. Often there are long hypoplastic segments as well as multiple areas of discrete stenosis. There is often an association with intrahepatic cholestasis (Alagille syndrome).

Stenosis of Main Pulmonary Artery

In stenosis of the main pulmonary artery, a constricting ring is usually present in the main pulmonary artery, either at or shortly beyond the tips of the pulmonic valve leaflets. This type of stenosis is commonly associated with rubella syndrome, and presents as a thick fibrous ring. In addition, children with peculiar facies and associated supravalvar stenosis without a history of rubella have been reported, and in them a thin supravalvar diaphragm is present. The clinical findings in this lesion are similar to those of valvar pulmonic stenosis, but the second heart sound is usually normal. The diagnosis can be made at cardiac catheterization or by echocardiography. Although balloon dilatation has been tried, results are poor. Optimal treatment is surgical patch repair. Immediate results are excellent, although there is a small incidence of restenosis at the patch site because of poor growth or scar tissue formation.

Peripheral Branch Stenosis

In the newborn period a physiological branch pulmonary arterial stenosis is present, and it accounts for innocent murmurs in many infants up to 6 to 12 months of age. True peripheral pulmonary arterial branch stenosis or hypoplasia may occur as an isolated defect or may be associated with underdevelopment of part or all of one lung or with underdevelopment of the right heart. Peripheral pulmonary arterial stenosis is frequently noted in infants with rubella syndrome, often in association with patent ductus arteriosus. Peripheral branch pulmonary arterial stenosis may also be found with other intracardiac congenital heart diseases, especially tetralogy of Fallot, and with Alagille’s syndrome.

The clinical features vary and may mimic either valvar pulmonic stenosis or a patent ductus arteriosus. The murmur is generally harsh and systolic and suggestive of pulmonic stenosis, but it usually has wider radiation into the infraclavicular regions (particularly toward the right) and the axillae; occasionally the murmur is continuous. The murmur is heard better in the axillae than at the base. The second heart sound is not consistently altered, and an ejection click is unusual. The electrocardiogram shows right ventricular hypertrophy in the more severe lesions; in rubella syndrome, left axis deviation is common. The chest roentgenogram may show right ventricular enlargement and occasionally shows multiple dilated pulmonary artery segments caused by poststenotic dilatation. If the peripheral stenosis involves only one lung or one segment of lung, undervascularization of that segment may be evident. Central stenoses may be shown by 2-dimensional echocardiography, but peripheral stenoses are not. Echocardiography is useful at assessing the significance of peripheral stenoses by estimating the right ventricular pressure. In addition, radionuclide pulmonary flow scans can demonstrate the presence and physiological significance of peripheral pulmonary artery stenoses. To define the location and anatomy of these defects, cardiac catheterization with angiography is necessary. Treatment depends on the severity and the number of stenoses; multiple peripheral lesions in the parenchyma of the lung are best treated with interventional catheterization techniques (see Chapter 499), whereas more central lesions may be relieved surgically. Transvascular placement of stents has markedly improved the ability to dilate branch pulmonary arteries and to maintain dilatation even of tortuous or kinked vessels; multiple as well as more peripheral stenoses are also manageable by this approach.

Persistent Pulmonary Hypertension in the Newborn

This syndrome, characterized by a high pulmonary vascular resistance and diminished pulmonary blood flow, is discussed in Chapter 50.

In the normal circulation, all the systemic venous return of desaturated or right-sided blood is directed via the right atrium and ventricle to the pulmonary arteries for oxygenation, and the fully saturated pulmonary venous blood is returned via the left atrium and ventricle to the aorta to provide oxygen for the body. Many congenital heart lesions are associated with redirection of some of the right-sided blood to the aorta, thus causing systemic arterial hypoxemia that leads to cyanosis. This pathophysiological process is called a right-to-left shunt. (Diversion of some of the oxygenated blood back into the lungs is termed a left-to-right shunt.) The pathophysiology and initial of congenital heart defects presenting in infancy with right-to-left shunts are discussed in detail in Chapter 483 and in additional text on the DVD. Specific lesions are further described below. An algorithm for approaching the clinical diagnosis of a newborn infant with cyanosis is presented in Table 483-6 and Chapter 49.

Pathophysiological Classification

Three pathophysiological groups are associated with right-to-left shunts. Each group has fairly reproducible pathophysiological processes that dictate the clinical presentation. The first group has a right-to-left shunt only. Because systemic blood flow is normal in these patients, the right-to-left shunt must necessarily decrease pulmonary blood flow—the less the pulmonary blood flow, the more the cyanosis. The second group has normal to increased pulmonary blood flow but is associated with cyanosis because the aorta is transposed over the ventricular septum. Thus, the aorta primarily receives systemic venous return, and the patient usually presents with severe cyanosis. The third group of defects not only has a right-to-left shunt and thus some systemic arterial desaturation but also has a left-to-right shunt. Frequently the blood is fully mixed in the heart, and the degree of cyanosis depends on the relative pulmonary and systemic blood flows. If neither circulation is obstructed, much more blood tends to be delivered to the lungs because, even at birth, pulmonary vascular resistance is less than systemic. The elevated pulmonary blood flow in these patients limits the degree of cyanosis, and their symptoms usually are related to the elevated pulmonary blood flow, which frequently causes respiratory symptoms and failure to thrive.

Pure Right‐to-Left Shunt (Decreased Pulmonary Blood Flow)

General

Pure right-to-left shunts occur when the inflow or outflow of the right side of the heart is redirected or obstructed or when one of the right-sided valves is regurgitant. It is best to think of this group of lesions along lines of blood flow (eTable 484.2). For example, the first level of redirection of flow is at the level of the systemic veins, some of which can flow directly into the left atrium, as occurs in an unroofed coronary sinus. The first level of obstruction or regurgitation within the heart is at the tricuspid valve. Obstruction may be caused either by complete absence of the valve (tricuspid atresia) or stenosis (hypoplastic right heart syndrome). Tricuspid regurgitation may be secondary to perinatal asphyxia, causing transient papillary muscle dysfunction, or may be secondary to a primary valve abnormality, as in Ebstein anomaly. Whatever the cause, right atrial pressure is elevated, and thus systemic venous blood is directed across the atrial septum to the left side of the heart and causes cyanosis. Obstruction of the outflow of the right ventricle can occur with a ventricular septal defect (tetralogy of Fallot) or without it (critical pulmonary stenosis or pulmonary atresia with intact ventricular septum). Pulmonary arterial stenoses usually occur in association with tetralogy of Fallot but can be isolated, as in Williams syndrome. Last, pulmonary arterial blood flow can be redirected just before it is about to reach the capillary bed for oxygenation, as occurs in pulmonary arteriovenous malformations.

Initial Presentation

The degree of cyanosis is determined by the amount of pulmonary blood flow in these patients. In neonates with critical obstruction or insufficiency, systemic arterial oxygen tension falls rapidly over the first hours or days of life, and prostaglandin E1 (PGE1) infusion is essential to maintain adequate pulmonary blood flow via the ductus arteriosus. In any newborn with significant cyanosis in the first hours of birth, infusion of PGE1 should be started immediately on the assumption that pulmonary blood flow is compromised. The primary complications of PGE1 are systemic vasodilatation and respiratory depression. As long as blood pressure is kept normal with volume infusion and vasoconstrictor support as necessary, and as long as ventilatory support is available in the event of respiratory depression, PGE1 is never absolutely contraindicated and may be life-saving in patients with decreased pulmonary blood flow. Oxygen therapy is of very limited value because pulmonary blood flow is decreased and pulmonary venous blood is nearly fully saturated, but it may increase oxygen content in the blood slightly by adding oxygen dissolved in the blood. If hemoglobin concentrations are low, blood transfusions can increase oxygen uptake in the lung by increasing the amount of hemoglobin to which the oxygen can bind.

Metabolic acidemia is rarely present unless the cyanosis is extremely severe. Prostaglandin E1 will usually rapidly increase pulmonary blood flow and lead to resolution of the acidosis, but if acidosis is moderately severe, intravenous infusions of sodium bicarbonate can be given. Undiluted molar sodium bicarbonate (1 meq/mL) is generally given to the neonate intravenously in 5-mL amounts. After each injection, arterial or mixed venous pH should be reassessed so that the time and amount of subsequent injections can be based on the response. The infant should also be kept at an optimal temperature (skin temperature about 36.5°C) to minimize oxygen needs. In the very sick infant, tracheal intubation, muscle paralysis with neuromuscular blocking agents, and mechanical ventilation may conserve energy and ensure the best possible ventilation. These very sick infants often have acute gastric dilatation, and removal of stomach contents and limitation of oral intake may be necessary to prevent aspiration.

Hypoglycemia is common because anaerobic metabolism accelerates glycolysis. Blood glucose levels should be checked early, and glucose infusions should be given if the levels are low. Hypocalcemia may occur and also should be treated.

Definitive diagnosis is usually made by echocardiography. Cardiac catheterization is rarely indicated except for those in whom the catheterization may be therapeutic (such as balloon pulmonary valvoplasty in infants with critical pulmonary stenosis or coil embolization of pulmonary arteriovenous malformations). Unlike patients with transposition of the great vessels, the atrial communication is usually large, and thus balloon atrial septostomy is rarely indicated. This is because the obstruction is present in utero, and thus a much larger amount of blood than the typical 35% to 45% of combined venous return crosses the foramen ovale to the left atrium and ventricle. The increased blood flow across the foramen ovale is thought to increase the size of the foramen ovale and lead to true secundum atrial septal defects in many infants. Diagnostic catheterization is generally reserved for patients with pulmonary arterial abnormalities (for example, patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals), because echocardiography does not afford a good view of the peripheral pulmonary vascular bed.

Long-Term Medical Therapy

Although most patients with cyanotic heart disease due to right to left shunting now undergo definitive or at least palliative procedures at a very early age to increase pulmonary blood flow and systemic arterial oxygen saturation to acceptable levels, some patients either do not present to medical care or are not amenable to corrective procedures. These patients have sequelae of chronic cyanosis. The most common group of patients with chronic, persistent cyanosis are those with severe tetralogy of Fallot (with or without pulmonary valve atresia) who have extremely abnormal pulmonary vascular beds that are unable to accept normal amounts of blood flow, so that the ventricular septal defect cannot be closed. Patients with inflow obstruction to the right side of the heart tend to progress to Fontan procedures at an early age so that cyanosis is resolved.

Polycythemia with increased hemoglobin and hematocrit is an important consequence of arterial oxygen desaturation; it is a hematopoietic adaptation to the hypoxic stimulus. The increased oxygen content achieved by this compensatory mechanism is advantageous until the hematocrit exceeds about 55%, when the effects of the high blood viscosity begin to outweigh the advantages of the increased circulating oxyhemoglobin. It is important that hypochromic microcytic anemia be recognized in the severely cyanotic patient with high erythrocyte counts but relatively normal hemoglobin and hematocrit levels; this anemia can easily be corrected by oral iron administration.

The increased blood viscosity in severe cyanotic polycythemia may cause cerebral, mesenteric, renal, or pulmonary thromboses. Dehydration increases the danger of thrombosis, and adequate fluid intake should be maintained, particularly during febrile illnesses and hot weather. Anemia (hypochromic microcytic) in association with hypoxemia has also been implicated, particularly in infants, as one mechanism for cerebrovascular accidents.

Brain abscesses may occur in patients with right-to-left shunts because bacteria usually filtered out in the pulmonary circulation may be shunted directly into the systemic circulation.

Cyanotic patients with long-standing severe polycythemia may have thrombocytopenia and abnormalities of the soluble coagulation system, particularly in the older patient; caution is advised in regard to excessive postoperative bleeding.

The prolonged and severe hypoxemia of cyanotic congenital heart disease often results in retarded physical growth that is most striking in the musculature. Preschool children with cyanotic heart disease, as a group, may have slightly lower IQ scores and may perform less well with perceptual motor tasks than do children with acyanotic heart disease.

Specific Lesions

Although there are a large number of congenital heart defects associated with decreased pulmonary blood flow, the most prevalent and representative of specific groups of lesions are presented below, based on levels of blood flow.145-152

Abnormal Systemic Venous Drainage

Abnormal systemic venous connections are sometimes associated with complex cyanotic malformations, but isolated abnormal systemic venous connections to the heart are rare and relatively occult causes of cyanotic congenital heart disease without any other abnormal clinical signs or findings. These abnormal connections include termination of the right or left superior vena cava, the inferior vena cava, or hepatic vein in the left atrium. A left superior vena cava usually drains into the heart via the coronary sinus, so that the drainage of left superior vena caval blood into the left atrium is often referred to as unroofed coronary sinus. Rarely, a large persistent eustachian valve directs blood from a normally connected inferior vena cava through the foramen ovale. Diagnosis may at times be suspected with careful 2-dimensional Doppler and color echocardiographic examination and 2-dimensional echocardiographic contrast studies, but appropriate venous angiography should be used to define operative possibilities.

Tricuspid Atresia

Tricuspid atresia constitutes 1% of all congenital heart disease in the first year of life. There is agenesis of the tricuspid orifice with no opening from the right atrium to the right ventricle, and the only outlet from the right atrium for systemic venous return is an interatrial communication, usually a widely patent foramen ovale. Mixing of the entire pulmonary venous return and systemic venous return occurs in the left atrium; consequently, systemic arterial oxygen desaturation depends on pulmonary blood flow. Left ventricular output is then distributed directly to the aorta and indirectly through a ventricular septal defect or patent ductus arteriosus to the pulmonary vascular bed. Pulmonary blood flow is usually severely diminished in tricuspid atresia because of the small, restrictive ventricular septal defect and the underdeveloped stenotic right ventricular outflow tract. Less often, if there is no ventricular septal defect, pulmonary atresia and an extremely hypoplastic right ventricle may be present; pulmonary blood flow must then come from the aorta via a patent ductus arteriosus or aortopulmonary collateral vessels. Increased pulmonary blood flow is uncommon in tricuspid atresia but may occur when the ventricular septal defect is large and the pulmonary outflow tract from the right ventricle is well developed, or when transposition of the great arteries is present and the pulmonary artery arises directly from the left ventricle.

Clinical Features

Intense cyanosis usually occurs within hours to days after birth as the ductus arteriosus begins to close, unless the ventricular septal defect and right ventricular outflow tract are widely patent. Right heart failure, manifested by hepatomegaly and occasionally by presystolic hepatic pulsations, is rarely present but will occur if right-to-left shunting is obstructed at the patent foramen ovale. The precordium is quiet. This is an important clinical finding and distinguishes tricuspid atresia from almost all other common forms of cyanotic congenital heart disease except for hypoplastic right heart syndrome. Neonates within this group with outflow obstruction, or neonates with transposition of the great arteries or bidirectional shunts, have either pressure or volume loading of the right ventricle and thus present with either normal or increased right ventricular impulses. There is usually a harsh systolic murmur along the left sternal border caused by flow through the ventricular septal defect and right ventricular infundibular stenosis. The second heart sound is narrowly split, with a soft pulmonary component. If the ventricular septum is intact, there may be no significant murmur or only the very faint continuous bruit of a small patent ductus arteriosus, and the second heart sound is single.

Roentgenography

The roentgenographic findings in the usual infant with tricuspid atresia and small ventricular septal defect include diminished pulmonary vasculature and a small heart with a distinctive rounded or apple configuration resulting from deficiency of the right ventricular and pulmonary artery segments.

Electrocardiography

The electrocardiographic findings of left superior axis deviation and left ventricular hypertrophy are helpful clues because the 2 most prevalent cyanotic heart lesions, tetralogy with diminished pulmonary blood flow and complete transposition of the great arteries with increased pulmonary blood flow, usually manifest right axis deviation and prominent right ventricular forces (both normal for a newborn). Right atrial hypertrophy with prominent peaked P waves in limb lead II is also common, and the P-R interval is often abnormally short. In tricuspid atresia with transposition of the great arteries, the QRS axis is usually in the left lower quadrant, but this is still relatively leftward as compared to a healthy newborn.

Echocardiography

The 2-dimensional echocardiogram readily establishes the absence of a tricuspid orifice and valve leaflet apparatus. Few infants survive beyond 6 months of age without surgical palliation, but for those who do, clubbing, polycythemia, and poor physical development may be apparent.

In contrast, infants with tricuspid atresia and large ventricular septal defect (often with transposition of the great arteries) present with increased pulmonary blood flow and show only minimal cyanosis after the newborn period. Congestive heart failure, with tachypnea, dyspnea, excessive perspiration, hepatomegaly, and pulmonary rales, appears by 3 to 6 weeks of age. The findings in these infants are those of a large left-to-right shunt: precordial hyperactivity, a long harsh pansystolic murmur along the left sternal border, and a prominent mid-diastolic rumbling murmur at the apex. Roentgenographic findings show increased pulmonary markings and a large cardiac silhouette because of left ventricular enlargement. There is an enlarged left ventricle and usually a hypoplastic right ventricular outflow tract. Tricuspid atresia variants with large ventricular septal defect or with transposition of the great arteries can easily be distinguished, as can more complex tricuspid (right- or left-sided AV valve) atresia malformations with ventricular and great artery inversion.

Cardiac catheterization is rarely indicated in the newborn period because the pulmonary arteries are normally developed and the foramen ovale is usually widely patent. Catheterization is generally reserved for the patient following palliative surgical procedures in anticipation of further surgery.

Treatment

Treatment of infants with tricuspid atresia and diminished pulmonary blood flow is surgical and often urgent. After the initial presentation of cyanosis and the subsequent institution of PGE1, the patient usually undergoes a palliative systemic-pulmonary shunt, a modified Blalock–Taussig anastomosis (with Gore-Tex conduit interposition). The operative survival is excellent (~95%) and with stable and prolonged augmentation of the pulmonary blood flow. In the older infant or young child, the shunt is replaced by a cavopulmonary connection that decreases the amount of blood returning to the left ventricle and thus its work. The typical procedure connects the superior vena cava directly to the main pulmonary artery, which is either banded or completely disconnected from the right ventricle (bidirectional Glenn procedure). A late complication reported with the Glenn shunt has been the occurrence of intrapulmonary arteriovenous shunts in dependent portions of the lungs or large superior-to-inferior vena caval collaterals, both with a resultant increase in cyanosis.

The young child, however, becomes more cyanotic over the next 2 to 4 years of life, as the lower body grows faster than the upper body. The modified Fontan-Kreuzer operation is the final palliative procedure in these children. It diverts the inferior vena caval return directly to the pulmonary arteries, either using an external conduit or a lateral tunnel within the right atrium. After this procedure, all systemic venous blood (except the relatively small coronary circulation, which returns directly to the heart via the coronary sinus) goes directly to the lungs so that the patients are no longer cyanotic. Success of the Fontan operation depends on appropriate selection of patients with adequate-sized pulmonary arteries, low pulmonary artery pressure and vascular resistance, and good left ventricular function without significant mitral regurgitation. The results can be very satisfactory, although there is concern about deterioration 15 years or more after the surgery. Heart failure and atrial arrhythmias are the most common late complications, and there is a significant late mortality secondary to these developments. Because the systemic venous pressure is always higher than normal, some patients develop protein-losing enteropathy that is also very difficult to manage. (See Chapter 498.)

The young child, however, becomes more cyanotic over the next 2 to 4 years of life, as the lower body grows faster than the upper body. The modified Fontan-Kreuzer operation is the final palliative procedure in these children. It diverts the inferior vena caval return directly to the pulmonary arteries, either using an external conduit or a lateral tunnel within the right atrium. After this procedure, all systemic venous blood (except the relatively small coronary circulation, which returns directly to the heart via the coronary sinus) goes directly to the lungs so that the patients are no longer cyanotic. Success of the Fontan operation depends on appropriate selection of patients with adequate-sized pulmonary arteries, low pulmonary artery pressure and vascular resistance, and good left ventricular function without significant mitral regurgitation. The results can be very satisfactory, although there is concern about deterioration 15 years or more after the surgery. Heart failure and atrial arrhythmias are the most common late complications, and there is a significant late mortality secondary to these developments. Because the systemic venous pressure is always higher than normal, some patients develop protein-losing enteropathy that is also very difficult to manage. (See Chapter 498.)

Neonates with tricuspid atresia, large ventricular defects, with or without transposition of the great arteries, present with markedly increased pulmonary blood flow and usually have early surgical palliation with pulmonary artery banding to restrict the pulmonary blood flow in order to prevent pulmonary vascular disease. Subsequent medical and surgical approaches to these patients are similar to those for the usual patient with tricuspid atresia.153-155

Ebstein Anomaly

This is a rare malformation in which the posterior and septal leaflets of the tricuspid valve are displaced downward and attached anomalously to the right ventricular wall. The abnormally placed tricuspid valve divides the right ventricle into a proximal “atrialized” segment and a distal functional ventricle. The atrialized ventricular segment and the right atrium together are usually enormously dilated, and there is severe tricuspid regurgitation. Hemodynamic abnormalities are related to the extent of the tricuspid regurgitation, to the small size of the remaining functional right ventricle and its outflow (which may be severely obstructed), and to the subsequent degree of right-to-left shunting through a patent foramen ovale.

Clinical Features

Wide variations in hemodynamic derangements cause the clinical symptoms to vary widely. In the most extreme lesions, severe tricuspid regurgitation presents in utero, and death occurs secondary to hydrops fetalis. Many neonates present with severe cyanosis. Although this decreases dramatically in the first few days of life because of the rapid perinatal decrease in the pulmonary vascular resistance, some have persistent severe cyanosis that requires placement of a systemic-pulmonary shunt. Those infants usually have severely hypoplastic ventricles and obstructed outflow tracts. The long-term approach for these patients is similar to that of tricuspid atresia or regurgitation, with a modified Fontan circulation being the final palliative procedure. In most patients, cyanosis resolves in the first few days of life and does not recur, if at all, until later childhood or young adulthood. Although there frequently is little limitation to activities during childhood, exercise tolerance eventually deteriorates. Episodes of paroxysmal supraventricular tachycardia occur in 20% to 25% of patients.

On auscultation a characteristic triple or quadruple heart sound rhythm overrides a soft high-pitched systolic murmur of tricuspid regurgitation. There is also a characteristic soft scratchy mid-diastolic murmur at the left sternal border and apex. The second heart sound is usually widely split with little respiratory variation. The roentgenographic findings include moderate or marked cardiomegaly with striking enlargement of the right atrium and usually diminished pulmonary vascular markings. The electrocardiogram may also be characteristic, usually showing right atrial hypertrophy, prolonged P-R interval, and incomplete or complete right bundle branch block patterns. Preexcitation patterns (Wolff-Parkinson-White syndrome) occur in about 10% to 15%. The 2-dimensional echocardiogram is diagnostic and shows a large tricuspid orifice with apical displacement of the septal leaflet of the tricuspid valve.

Treatment

Moderate congestive heart failure can be effectively treated with digitalis and diuretics, and disturbing dysrhythmias can usually be controlled pharmacologically or sometimes by ablating accessory pathways. Surgical treatment is seldom necessary in infancy or childhood. When major tricuspid regurgitation is associated with progressive congestive heart failure, surgical maneuvers directed at realigning the tricuspid valve leaflets to their true annulus, resecting redundant atrialized tissue, or placing a prosthetic tricuspid valve have been done with reasonably satisfactory functional results.

The life expectancy of the patient with Ebstein anomaly varies widely, depending on the severity. Because the pathologic substratum is so variable, management of these patients must be individualized. The usual cause of death is congestive heart failure in the second or third decade of life. In the child or young adult, the more severe the cyanosis the poorer the prognosis; the onset of florid congestive heart failure is usually followed by death within a few years.156-160

Pulmonary Atresia with Intact Ventricular Septum

Two percent of infants who present with severe congenital heart disease in the first year after birth have pulmonary atresia or critical pulmonary valve stenosis with intact ventricular septum. The majority have a hypoplastic but thick-walled right ventricle with a markedly hypoplastic tricuspid orifice and valve. About 15% have a right ventricle of normal or large volume, with tricuspid valve incompetence, and these often have critical stenosis rather than atresia. Intermediate forms occur. In all of the patients there is little or no blood flow across the pulmonary valve; rather, systemic venous return crosses the atrial septum to the left heart and the aorta. The pulmonary circulation is sustained primarily through a patent ductus arteriosus.

Clinical Manifestations

Cyanosis occurs early in the neonatal period, and these infants usually deteriorate rapidly and die unless PGE1 is started. Gross cardiac failure occurs rarely, and only if there is severe tricuspid incompetence. Similar to tricuspid atresia, the precordium is quiet unless there is marked tricuspid incompetence. If murmurs are heard, they are usually faint. A soft systolic blowing murmur, representing insufficiency of the hypoplastic tricuspid valve, may be heard along the lower left and right sternal borders; a soft continuous bruit of a small patent ductus arteriosus may be heard at the upper left sternal border. The second heart sound at the pulmonary area is single, reflecting only aortic valve closure. On chest roentgenogram, the infant with a markedly hypoplastic tricuspid orifice shows a small heart; diminished pulmonary vascular markings are the rule, except rarely with a large persistent patent ductus arteriosus or with an infusion of PGE1. Even with high pulmonary blood flow, however, the central arteries are not large, so the pulmonary vascular markings may appear diminished. Infants with marked tricuspid insufficiency and large right ventricular and atrial volumes have gross cardiomegaly. On the electrocardiogram, left ventricular hypertrophy is common in the first days or weeks of life, but right ventricular hypertrophy becomes evident as the right ventricular muscle hypertrophies further. In contrast to tricuspid atresia, where there is continuing left ventricular hypertrophy and usually a superior left QRS axis deviation, the infant with pulmonary atresia shows an inferior QRS axis and right ventricular hypertrophy. A 2-dimensional echocardiogram shows the small right ventricle, hypoplastic tricuspid valve, pulmonary valve atresia, and intact ventricular septum. Doppler interrogation sometimes documents retrograde right ventricular coronary sinusoid-to-coronary artery blood flow in systole and may demonstrate flow across the pulmonary valve if there is critical pulmonary stenosis rather than atresia. In contrast to many other lesions, cardiac catheterization is indicated in all patients with pulmonary atresia/critical pulmonary stenosis for both diagnosis and therapeutic reasons. Catheterization shows right atrial hypertension, a massive right-to-left interatrial shunt, and right ventricular hypertension, often with peak systolic pressures far greater than systemic. A right ventricular selective angiogram establishes the diagnosis by demonstrating the obstruction between the right ventricle and the pulmonary artery, and the extent of hypoplasia of the ventricular cavity and tricuspid orifices. In ventricular systole, intramyocardial sinusoids may fill from the dead-end right ventricular cavity and drain retrograde into the coronary arterial system.

Occasionally, there is no connection between some of these coronary arteries and the aorta; this is called a right ventricular dependent coronary circulation. Although the prognosis for pulmonary atresia in general is poor, with midterm survival in the 60% to 80% range, the prognosis for infants with a dependent coronary circulation is particularly poor, so it should be sought out in every patient. The pulmonary artery will be seen to fill through a tortuous ductus arteriosus. Pulmonary valvoplasty is attempted in most of these patients, even with atretic valves, as discussed below.

Treatment

Immediate intravenous infusion of PGE1 on diagnosis has greatly improved outcome in these patients. At catheterization an attempt at pulmonary valvoplasty is made, even if the valve is atretic, except when the tricuspid valve and right ventricle are so diminutive that they cannot contribute significantly to the circulation. If a valvoplasty is successful, PGE1 is continued for several days because the severe right ventricular hypertrophy prevents adequate filling and the patient remains ductus dependent for adequate pulmonary blood flow. However, the ventricle remodels rapidly if the obstruction is relieved, and the PGE1 usually can be discontinued within a week.

If the valvoplasty is unsuccessful or considered inadequate after 7 to 10 days, surgery is indicated. Patients in whom a right ventricular outflow tract is identified angiographically should have a pulmonary valvotomy performed. A small right ventricular cavity alone does not preclude executing a valvotomy. However, if the coronary arterial supply is mainly from sinusoids, decompression of the right ventricle must be avoided. In infants with an adequate right ventricular size, pulmonary valvotomy alone is advised, but PGE1 infusion is continued for a few days postoperatively as in pulmonary valvoplasty. If the right ventricle is considered inadequate initially or after several days, a systemic-pulmonary shunt is also performed. In some centers, the ductus is kept open with a stent, but the role of this vis-a vis a surgical shunt has not been defined. The valvotomy permits the right ventricle to eject some blood and promotes progressive chamber enlargement, whereas the shunt initially provides the bulk of increased pulmonary blood flow that is essential for survival. The pulmonary valvotomy and shunt performed in the neonatal period for this malformation usually do not provide optimal long-term results. Reoperation 3 to 5 years later usually becomes necessary because of persistent or recurrent right ventricular outflow tract obstruction. The second-stage operation involves right ventricular outflow tract reconstruction and placement of an outflow patch graft with ligation of the shunt. If the right ventricle remains inadequate, either a bidirectional Glenn procedure is performed so that the right ventricle handles only inferior vena caval blood or, in the worst patients, a modified Fontan-Kreuzer procedure is done.161-167

Tetralogy of Fallot

Tetralogy of Fallot is the most common cyanotic heart lesion encountered in untreated patients with cyanotic congenital heart disease who survive beyond infancy. Four structural abnormalities constitute the tetralogy: right ventricular outflow tract stenosis, ventricular septal defect, dextroposition of the aorta, and right ventricular hypertrophy. There is wide anatomic variation, with resultant physiological and clinical variations.

The basic lesion is anterocephalad malalignment of the outlet septum relative to the muscular septum. This is associated with unequal division of the truncus arteriosus into small pulmonary and large aortic components. The malalignment together with secondary hypertrophy of the muscle form the primary site of obstruction to blood flow in the infundibulum or outflow tract of the right ventricle. In addition, the pulmonary valve is often stenotic, and the pulmonary valve annulus and pulmonary arteries are often hypoplastic. In the most severe form (tetralogy of Fallot with pulmonary atresia), the distal infundibular outflow tract and pulmonary valve are atretic, and the pulmonary artery and main pulmonary arterial branches may be severely hypoplastic or atretic. Often, large aortopulmonary collaterals supply most of the lung. The ventricular septal defect is usually large, perimembranous with outlet extension, and near the tricuspid and aortic valves. The aorta arises directly over the ventricular septal defect; the degree of overriding varies greatly.

Because of the pulmonary outflow tract obstruction, varying amounts of systemic venous blood are shunted across the ventricular septal defect into the aorta, resulting in cyanosis. Pulmonary artery pressure and pulmonary blood flow are reduced.

Clinical Features

The clinical findings at birth vary with the severity of the pulmonary stenosis, but few infants with the tetralogy of Fallot remain asymptomatic or acyanotic. Cyanosis may not be present at birth; as long as the ductus arteriosus remains patent, there may be adequate pulmonary blood flow, or the outflow tract obstruction may not be severe at birth. Hypercyanotic episodes with paroxysmal hyperpnea may occur spontaneously or after early morning feedings or prolonged crying. The attacks may last only a few moments and have no sequelae; they may cause obtundation, limpness, deep exhaustion, or sleep; rarely, they may end in unconsciousness, convulsions, or even death. Because approximately one third of patients with the tetralogy of Fallot begin to have hypoxic spells by 4 or 5 months of age, corrective surgery is usually done electively within a few months of birth. Thus, the pediatrician rarely sees these episodes any more. A few of these infants have minor spells. Their cyanosis may not increase much, but they cry inconsolably. They are often misdiagnosed as “colic.” Putting them on the abdomen with a knee chest position aborts the crying (see below) and makes the diagnosis. In the very rare instance in which an infant does not undergo correction, exercise tolerance in the child varies in proportion to the severity of the cyanosis. Young children with the tetralogy of Fallot and severe cyanosis often adopt a characteristic squatting position after exertion. This maneuver increases, arterial oxygen saturation, probably by increasing systemic arterial resistance. A final group of patients shows little or no evidence of cyanosis in infancy or early childhood (acyanotic Fallot); cyanosis on exertion gradually becomes more manifest as they grow older. Occasionally, even in this group, very rapid clinical change toward the classic severely cyanotic tetralogy can occur.

In the rare, untreated patient, major late complications include brain abscess, cerebral thrombosis with hemiplegia, and infective endocarditis. Growth and development are generally delayed in proportion to the degree of cyanosis. Infective endocarditis is particularly common in children who have palliative systemic-pulmonary shunts rather than correction. Prophylactic antibiotic therapy is no longer routinely recommended for most of these patients (see Chapter 490).

Physical examination shows a right ventricular systolic heave along the lower left sternal border. A single loud second heart sound corresponding to aortic valve closure is generally heard best at the lower left sternal border, rather than being heard best at the upper right or both the upper right and left sternal border. This physical sign is important, especially in a neonate when trying to differentiate an acyanotic tetralogy of Fallot from a ventricular septal defect. When closure of the pulmonary valve is audible at the upper left sternal border, it is delayed and diminished in intensity. In patients with moderate right ventricular outflow tract obstruction, the systolic murmur is loud and harsh, stenotic or pansystolic in quality, and best heard at the middle or lower left sternal border. Rarely, a continuous murmur of persistent ductus arteriosus is heard at the upper left sternal border.

The heart is of normal size, and lung fields are poorly vascularized, signifying diminished pulmonary blood flow. The right ventricular outflow tract and main pulmonary artery segments are usually hypoplastic, resulting in a concavity of the upper left margin of the cardiac silhouette instead of the normal convexity. A characteristic “sheep’s nose,” “coeur en sabot,” or boot-shaped heart may be present, particularly with pulmonary atresia. The ascending aorta is generally large. In about 25% of the patients, a right-sided aortic arch is present and is recognized by observing a right-sided rather than left-sided indentation on the trachea. The superior vena caval shadow may be displaced to the right. When bronchial collateral circulation is well developed, diffuse fine vascular markings are noted throughout the lung. Rarely, markedly decreased left lung vascular markings indicate absence or stenosis of the left pulmonary artery.

There are right axis deviation and right ventricular hypertrophy, although in the newborn infant the diagnosis of pathologic right ventricular hypertrophy by electrocardiogram is more difficult because of the normal right ventricular dominance at this age.

In tetralogy of Fallot, the dilated aortic root overrides a large adjacent ventricular septal defect, and varying degrees of right ventricular infundibular obstruction, pulmonary valve stenosis, and hypoplasia or narrowing of the main pulmonary artery and left pulmonary artery are revealed. Doppler examination confirms the severity of the obstruction and demonstrates systolic turbulence in the main pulmonary artery.

The acute severe episodes of dyspnea and hypoxemia, termed blue spells or hypercyanotic episodes, in some infants with the tetralogy reflect a further acute reduction in the pulmonary blood flow. These spells may occur even if the infant is not cyanotic at rest. The precipitating mechanisms are probably multiple: prolonged crying may decrease pulmonary blood flow because of prolonged expirations; decreases in right ventricular preload and systemic vascular resistance because of sleeping, fever, or spontaneous vasomotor changes decrease pulmonary blood flow and increase the right-to-left shunt; and constriction of the right ventricular infundibulum may occur, further decreasing pulmonary blood flow, although it is uncertain whether this truly occurs.

Treatment

As with many significant congenital heart abnormalities, the treatment is ultimately surgical. For the neonate with prominent cyanosis, prompt infusion of PGE1 is important. Corrective surgery is usually performed within 2 to 4 months of birth, but in the rare patient who has not had palliative or corrective surgery, medical therapy is primarily directed toward acute relief of hypercyanotic episodes and preventing the complications of right-to-left shunts.

Hypercyanotic episodes may be treated by placing the infant on the abdomen in a knee-chest position or holding the infant with the legs flexed on the abdomen. Oxygen should be given to lessen dyspnea and cyanosis but is not very helpful because of the very low pulmonary blood flow. Morphine sulfate (0.2 mg/kg body weight subcutaneously) is especially effective in terminating a prolonged or severe attack. If the spell is protracted and severe and does not respond to the foregoing therapy, metabolic acidemia ensues, and correction with intravenous sodium bicarbonate is essential. Vasopressors can be given either early in the attack or if other therapy fails; phenylephrine, 0.02 mg/kg IV or 0.1 mg/kg IM, will raise systemic resistance and thus increase pulmonary blood flow. If possible, it should be given by continuous intravenous infusion, generally at a dose of 2 to 5 μg/kg/min. In infancy, these attacks may be precipitated by a relative iron-deficiency anemia (hypochromic microcytic), and such patients should have iron therapy until the hematocrit reaches levels of 50% to 55%. Further increase in the hematocrit results in a marked rise in blood viscosity, with progressive impediment to blood flow and risk of cerebral thrombosis. Any hypercyanotic episode is an absolute indication for surgery, so it is now rare to need to treat anemia except in the immediate preoperative period. If surgery is contraindicated for some reason, oral propranolol has been given at a dosage of 0.5 to 1.0 mg/kg orally every 6 hours to prevent or reduce the frequency of paroxysmal dyspneic attacks. Some cardiologists have reported that balloon dilatation of the infundibulum and pulmonary valve may improve pulmonary blood flow enough so that surgery can be delayed for 6 to 12 months.

Early elective surgery is indicated for infants with tetralogy of Fallot or tetralogy with pulmonary atresia, even in the absence of symptoms. Patients with the tetralogy of Fallot and patent right ventricular outflow tracts can have intracardiac surgical repair of the malformation by skilled congenital heart surgeons in the first months of life with an operative mortality under 5%. The ventricular septal defect is closed, the infundibular muscle is resected, and sometimes right ventricular outflow and main pulmonary artery patches are placed to augment the outflow tract. Pulmonary valvotomy is also performed in most patients, but enlargement of the pulmonary valve annulus with a transannular patch is avoided unless the annulus is critically small. Rarely, an infant cannot be repaired because of marked pulmonary artery hypoplasia, and a systemic-pulmonary anastomosis or a right ventricular outflow patch is performed without closure of the ventricular septal defect. Balloon dilatation of the pulmonary arteries can then be performed in the catheterization laboratory in anticipation of later correction.

Although repair of tetralogy of Fallot with pulmonary atresia has in recent years become increasingly successful, the operative risk and late complications and death are higher than for uncomplicated tetralogy. Unifocalization of the often discontinuous sources of pulmonary blood flow to a central system is required before the standard repair. This may be done in one or multiple stages. The 10- and 20-year survival rates excluding operative and early hospital deaths are approximately 80% and 65%, respectively, as against 95% for simple tetralogy over the same intervals.

Surgical correction for most patients with uncomplicated tetralogy of Fallot results in excellent, long-lived functional results with over 90% freedom from reoperation. Residual or recurrent small left-to-right shunts are uncommon, but residual mild or moderate right ventricular-pulmonary outflow tract obstruction and regurgitation are common. Those who have marked pulmonary regurgitation and very dilated right ventricles may eventually develop congestive heart failure, and may be at higher risk for sudden death, especially if they have very wide QRS intervals. These patients are candidates for pulmonary valve replacement, currently performed surgically but in the future very likely by catheter insertion. A few patients have surgically induced complete atrioventricular block and require an implanted pacemaker. About 1% to 3% have serious late dysrhythmias, particularly ventricular tachycardia, probably related to reentry mechanisms at the site of right ventricular tissue excisions, and about 1% to 2% die suddenly, presumably from dysrhythmias. Dysrhythmias should be suspected if these patients after surgery complain of dizzy spells, syncope, or palpitations, and appropriate diagnostic studies and therapy applied.

Tetralogy-Like Lesions

The clinical findings in patients with double-outlet right ventricle, single ventricle, or d- or l-transposition of the great arteries with a ventricular septal defect, when associated with severe pulmonic or subpulmonic stenosis, may closely resemble the findings in tetralogy of Fallot. These other malformations can be diagnosed with ease by 2-dimensional and Doppler echocardiography.168-177

Pulmonary Arteriovenous Malformation

Occasionally fistulas connect pulmonary artery and vein so that some pulmonary blood flow bypasses the alveoli. The fistulas may be large and discrete, single or multiple, or there may be numerous small fistulas scattered throughout the lungs. Many of these fistulas occur in patients with Osler-Rendu-Weber syndrome (hereditary hemorrhagic telangiectasia). They are frequently complicated by brain abscess, hemoptyisis, or intrapleural hemorrhage. Coil embolization of the fistulas can be performed in the catheterization laboratory to improve arterial oxygen saturation, although fistulas may occasionally recur in the same or other lung segments.

The second major group of congenital heart defects that present with severe cyanosis in the newborn period has the common finding that the aorta is malposed across the ventricular septum to arise from the right ventricle. This malposition occurs in such a manner (anterior and to the right with situs solitus) that the aorta is committed to receiving systemic venous return. Thus, even with a very large pulmonary blood flow, the patient can be very cyanotic. The most common heart lesion with aortic malposition is complete d-transposition of the great arteries. In this defect, the pulmonary artery is also malposed, arising from the left ventricle. In most patients, the ventricular septum is intact. Because the great vessels arise from the inappropriate ventricles, these are discordant ventriculoarterial connections. The atrioventricular connections, however, are normal (concordant).

Initial Presentation

In the absence of a ventricular septal defect, the aorta receives all of the desaturated systemic venous return and can receive pulmonary venous blood only via an interatrial communication. However, these infants often do not have atrial septal defects. Thus, as occurs normally, pulmonary blood flow increases dramatically at birth, and the increase in pulmonary venous return tends to close the foramen ovale. If this occurs, the neonate with transposition may become critically cyanotic soon after birth, a problem intensified by closure of the ductus arteriosus. If this occurs, an emergency atrial septostomy to establish an atrial left-to-right shunt should be performed. In the interim, particularly if the infant is not at a major medical center with a neonatal cardiology program, PGE1 can be very beneficial by increasing pulmonary blood flow, which in turn increases pulmonary venous return and left atrial pressure and thus forces pulmonary venous blood to cross to the right atrium. This may be life saving but may occur at the expense of very high left atrial pressures. Thus, the neonate should be intubated if there are signs of any respiratory compromise. In addition, immediate supportive therapy for metabolic acidemia and maintenance of body temperature should be instituted.

Balloon atrial septostomy is performed via the femoral or umbilical vein during neonatal cardiac catheterization or even under echocardiographic visualization in the intensive care nursery. A transvenously introduced catheter bearing a balloon is advanced through the foramen ovale into the left atrium, where the balloon is inflated to a diameter of 8 to 10 mm. The catheter and inflated balloon are then abruptly withdrawn into the right atrium, thus rupturing the septum primum valve of the fossa ovalis, enlarging the interatrial communication, and providing for more adequate mixing of blood. The systemic arterial oxygen tension often rises initially, but if it remains low despite PGE1 and an adequate balloon septostomy, a transfusion of blood is often helpful. By increasing circulating volume and atrial pressures, a transfusion can dramatically increase the left-to-right atrial shunt. In a few infants shunting is minimal because of pulmonary arterial hypertension, and treatment with nitric oxide, sildanefil, or even extracorporeal membrane oxygenation (ECMO) might be required. After a few days of stabilization, almost all infants with simple transposition today undergo surgical repair.

In order to consider this group of lesions along lines of blood flow, one has to make the initial assumption that the aorta is committed to the systemic venous (right) ventricle and then consider blood flow from the right atrium onward. Defects in the atrial, atrioventricular, and ventricular septa may occur, the latter of which is frequently associated with either pulmonic stenosis or with double-outlet right ventricle (Taussig-Bing anomaly), which is associated with aortic outflow obstruction.

Complete (D-) Transposition of Great Arteries

Complete transposition of the great arteries is the most common cardiac cause of cyanosis in the neonate, and until recently it accounted for the majority of deaths in infants with cyanotic congenital heart disease under 1 year of age. Once almost universally fatal, the prognosis has changed dramatically in recent years with the introduction of palliative and corrective procedures. This disorder is discussed in Chapter 483 and further in material on the DVD.

Morphology and Physiology

In complete transposition of the great arteries, the systemic venous return traverses the right atrium and right ventricle and is ejected into the transposed aorta arising from the right ventricle; the pulmonary venous return traverses the left atrium and left ventricle and is ejected back into the lungs via the transposed pulmonary artery. There are thus 2 separate circulations in parallel instead of in series. This arrangement is incompatible with life without some communications to permit oxygenated pulmonary venous blood to enter the systemic circulation and systemic venous blood to enter the pulmonary circulation. In about 70% of patients with complete transposition, the ventricular septum is intact, and intracardiac shunting occurs only through a stretched foramen ovale or, rarely, a secundum atrial defect; consequently, cyanosis is extreme. Infants with an associated large ventricular septal defect have better mixing between the 2 circulations and so have higher systemic oxygen saturations. Although a patent ductus arteriosus may be demonstrated in about half of the newborn infants with transposition, it closes functionally and anatomically soon after birth in most patients. A persistent large patent ductus arteriosus is uncommon, particularly malignant in terms of the risk of severe pulmonary vascular disease, and requires prompt recognition and therapy. Left ventricular outflow tract stenosis of varying degrees also may be present; it most often results from a fibrous ridge or collar in the outflow tract of the left ventricle. Common atrioventricular canal, atrioventricular valve atresia, severe pulmonary valve stenosis or atresia, coarctation of the aorta, or right aortic arch is rare in complete transposition of the great arteries.

The major consequences of transposition of the great arteries are severe hypoxemia, metabolic acidemia, and congestive heart failure. The level of systemic arterial oxygen saturation depends on the transfer of oxygenated pulmonary venous blood to the systemic circuit as well as the reciprocal transfer of systemic venous return to the pulmonary circuit. These transfers are a function of the size of the shunting sites: foramen ovale, ostium secundum defect, ventricular septal defect, patent ductus arteriosus, and bronchial collateral circulation. Other important factors, particularly in patients with large ventricular septal defect, are the hemodynamic consequences of pulmonary outflow tract stenosis and increased pulmonary vascular resistance; if outflow resistance is high, it will restrict the pulmonary blood flow and the volume of the oxygenated pulmonary venous return and reduce the systemic arterial oxygen saturation. The existence of the systemic and pulmonary circulatory pathways in parallel instead of in series usually results in high cardiac outputs for both the right and left ventricles, with consequent cardiac dilatation and myocardial failure. Myocardial function can be further compromised by the markedly desaturated aortic blood flow entering the coronary circulation.

Pulmonary vascular obstructive disease has been observed both by microscopy and by cardiac catheterization to be more common and to progress at an unusually rapid rate in infants with transposition of the great arteries and large ventricular septal defect, as contrasted to infants with large ventricular septal defect and normally related great arteries. About 75% of all infants with transposition of the great arteries and large ventricular septal defect older than 1 year of age have advanced pulmonary vascular obstructive disease, and histologic studies demonstrate moderate pulmonary vascular disease lesions in many infants with large ventricular septal defect by 3 to 4 months of age. Associated pulmonic stenosis, early intracardiac correction with closure of the ventricular septal defect, or early surgical pulmonary artery banding protects against the development of pulmonary vascular obstructive disease in this lesion. Accordingly, palliative pulmonary artery banding or intracardiac repair should be considered before the patient is 3 to 4 months of age. Significant pulmonary vascular obstructive disease has even been seen in about 5% of the transposition patients with intact ventricular septum who survive early infancy.

Clinical Manifestations

Most infants with an intact ventricular septum become critically ill the first few hours after birth, but if there is a large ventricular septal defect, cyanosis may be slight, and congestive heart failure may not become evident until a few weeks after birth. Characteristically, attention is first directed to the infant with inadequate intracardiac mixing by nursery personnel who observe cyanosis in an otherwise apparently healthy infant. A high index of suspicion is needed for early diagnosis; except for persistent cyanosis and progressive hyperpnea in the first hours after birth, the infant may appear well developed and minimally distressed, there are no distinctive murmurs, and the chest roentgenogram and electrocardiogram may be deceptively normal.

On auscultation, the second heart sound is usually interpreted as loud and single and is heard best usually at the upper left rather than the upper right sternal border, but careful auscultation often reveals narrow splitting with a soft pulmonary valve closure. The murmurs are usually unimpressive in the newborn with an intact ventricular septum, but there may be a short grade 2 to 3/6 ejection systolic murmur at the middle of the left sternal border. A loud harsh systolic murmur in a slightly older infant usually indicates a ventricular septal defect or left ventricular outflow tract stenosis.

Infants with transposition of the great arteries and large ventricular septal defect develop prominent cardiac failure and modest cyanosis by 3 to 4 weeks of age. Increasing tachypnea, dyspnea, and excessive perspiration are noted. Cyanosis may increase, but often it remains relatively mild because of good circulatory mixing. Pulmonary rales and hepatomegaly may be striking.

The electrocardiogram may not be helpful in the newborn infant because it shows right axis deviation and right ventricular hypertrophy of a degree that may be normal for a neonate. After 5 days of age, however, persistence of a positive T wave over the right precordium suggests abnormal right ventricular hypertrophy. In the older infant with an intact ventricular septum, right atrial hypertrophy and overt right ventricular hypertrophy are present.

The roentgenographic findings can vary from near normal to grossly abnormal. In the neonate the heart is small, but it enlarges over the first 1 to 2 weeks after birth. The classic transposition cardiac silhouette, an egg-shaped or oval heart with a narrow superior mediastinum and small thymic shadow, is diagnostic, but it is present early in only about one third of the newborn infants.

Two-dimensional and Doppler echocardiography constitute the major tools for morphologic diagnosis and functional assessment, showing the transposed great arteries, with the aorta arising anterior and to the right from the morphologic right ventricle, and the pulmonary artery arising posterior and to the left from the morphologic left ventricle. The sites, direction, and magnitude of shunts can be seen, and assessments of ventricular pressures can be made.

Cardiac Catheterization

Cardiac catheterization in the neonate plays an important therapeutic role in effecting hemodynamic and clinical improvement by doing a balloon atrial septostomy. Often the procedure is performed under echocardiographic guidance at the bedside, and limited diagnostic data are obtained. If it is performed in a catheterization laboratory, hemodynamic data show that oxygen saturation of the blood in the pulmonary artery is higher than that in the aorta. In the immediate newborn period, if the ventricular septum is intact, the left ventricular systolic pressure may equal right ventricular systolic pressure; however, after a few days, left ventricular pressure usually falls to one half or less of right ventricular pressure unless some left ventricular outflow tract obstruction is present. A pressure difference across the atrial septum is common, with left atrial pressures exceeding those on the right, before the balloon septostomy.

Selective right ventricular angiography demonstrates the high anterior position of the aorta arising from the right ventricle, the status of the ventricular septum, and the ductus arteriosus. Selective left ventricular angiography demonstrates a pulmonary artery arising from the posterior ventricle, the status of the ventricular septum, and any left ventricular outflow tract stenosis.

Treatment

After initial stabilization with balloon atrial septostomy, PGE1 infusion, intubation and ventilation, and correction of any metabolic derangements, the patient is allowed to stabilize for a few days. During that time, full evaluation of associated lesions and coronary arterial anatomy is made. In the absence of lesions such as subpulmonary or pulmonary valve stenosis, arterial switch surgery is performed. It is now the treatment of choice, primarily because it returns systemic ventricular function to the left ventricle and because midterm follow-up studies indicate preservation of normal ventricular function and no significant incidence of postoperative arrhythmias. The operation involves transecting the great arteries, switching their attachments above the semilunar valves, and transplanting the coronary arteries from the preoperative anterior aortic root (new pulmonary root) to the preoperative posterior pulmonary arterial root (new aortic root). For infants with intact ventricular septum or an insignificant ventricular septal defect, it is critical to perform this operation under 8 weeks of age while the left ventricular pressure and muscle mass have not yet regressed to those of a low pressure, thin-walled pulmonary ventricle dictated by the transposition physiology. Current experience for the one-stage arterial switch repair in neonates in centers with neonatal cardiac surgical proficiency indicates early operative survival of 95% or more. Freedom from reoperation (most often done to relieve surgically induced supravalvar pulmonic stenosis) is also 90% to 95%. For the infant with complete transposition and a large ventricular septal defect, the primary management problems are left ventricular failure and pulmonary hypertension with the early onset of pulmonary vascular disease. Occasionally there may be myocardial ischemia caused by coronary arterial problems associated with the switch. Currently, neonatal arterial switch repair with closure of the ventricular septal defect has significantly improved the prognosis for this subset of transposition patients to about 90% survival over 5 years.

Transposition of the Great Arteries with Pulmonary Stenosis

In the infant with transposition of the great arteries and intact ventricular septum, slight or moderate left ventricular outflow tract stenosis may be present or develop in the subpulmonary region. This obstruction may be predominantly muscular and dynamic or predominantly fibromuscular and fixed. The degree of obstruction is usually modest and only severe degrees of anatomic obstruction should be relieved by resection or conduit bypass at the time of the open-heart procedure.

When a ventricular septal defect is present with severe subvalvar left ventricular outflow tract stenosis, the clinical picture may mimic the tetralogy of Fallot. Symptoms may begin at birth, with severe cyanosis and paroxysmal hypoxemic spells; the pulmonary vascular markings on the roentgenogram are decreased. If the pulmonary stenosis is not severe, cyanosis and clinical symptoms are not extreme initially, but they may become so as the infant matures. Two-dimensional echocardiography and selective left ventriculography can define the extent and site of the pulmonary stenosis.

In the extremely cyanotic newborn infant with transposition and severe subpulmonary or pulmonary stenosis or atresia, the safest treatment is to perform a systemic-pulmonary shunt. Intracardiac repair is difficult and should be postponed until past the age of 1 to 2 years. Surgical repair (Rastelli procedure) consists of repair of the ventricular septal defect with an intracardiac ventricular baffle so as to connect the left ventricle to the aorta. Then an extracardiac valve-bearing conduit is placed between the right ventricle and the distal stump of the pulmonary artery, to bypass completely the severely stenosed left ventricular outflow tract. Other surgical procedures are the Lecompte and Nikaidoh operations. In the Lecompte operation, the conal septum is removed so that the baffle connecting the left ventricle to the aorta is not obstructed, and the pulmonary trunk is disconnected from the left ventricle and pulled across to connect to the right ventricle, usually without a pulmonary valve. The Nikaidoh operation dissects the whole aortic root off the right ventricle and connects it to the left ventricle; the ventricular septal defect is closed with a patch, and the pulmonary artery is connected to the right ventricle either directly or with a conduit. Both these latter operations have better midterm results than the original Rastelli operation.178-183

Taussig-Bing Anomaly

Double-outlet right ventricle (DORV) is a rare group of lesions that is one of the types of malposition of the great arteries. Both the aortic and pulmonary valves are positioned over the right ventricle, there is often conal (outlet septum) tissue below both orifices, and the only outflow from the left ventricle is through the ventricular septal defect, which may be either subpulmonary or subaortic, or rarely uncommitted. When the pulmonary artery is committed to the right ventricle and the aorta overrides the ventricular septal defect, there is usually subpulmonic stenosis, and the physiology and treatment are similar to tetralogy of Fallot. When the aorta is committed to the right ventricle and the pulmonary orifice is related to and overriding the ventricular septal defect (Taussig-Bing anomaly), the hemodynamics and clinical findings are similar to those of transposition of the great arteries with large ventricular septal defect and pulmonary hypertension. An associated coarctation of the aorta is present in about 25% of these patients.

Corrective surgical procedures are increasingly successful for Taussig-Bing anomaly. Arterial switch repair as for complete transposition is the operation of choice, providing the great arteries are not too different in diameter, with early and midterm outcomes similar to those of transposition with a large ventricular septal defect. Any aortic arch abnormalities are corrected surgically either before or at the same time as the intracardiac repair. When the arterial size discrepancy is severe or intracardiac anatomy makes correction problematic, a pulmonary artery band is often performed at the same time as the aortic arch repair, and definitive surgery is delayed until a later date.

In this group of lesions, systemic arterial desaturation is present because some of the systemic venous blood is directed out the aorta. However, pulmonary venous blood also is directed back to the pulmonary arterial circulation. When there is no obstruction to either circulation, usually far more blood passes into the pulmonary circulation. This occurs whether the shunt occurs at the level of the veins, atria, ventricles, or great arteries. The pathophysiology of these disorders is described further in Chapter 483. Specific lesions associated with bidirectional shunting are listed in Table 483-5 and are described below.

Total Anomalous Pulmonary Venous Connection

Total anomalous pulmonary venous connection accounts for about 2% of all congenital heart malformations seen in the first year of life and is characterized by absence of any direct connection between the pulmonary veins and the left atrium. The pulmonary veins are connected either directly to the right atrium or to various systemic veins draining toward the right atrium, such as right superior vena cava, azygous vein, left innominate vein, coronary sinus, ductus venosus, or various combinations of these connections. The pulmonary veins almost always come together to form a common channel that lies behind but is separate from the left atrium. This proximity provides the key to successful corrective surgery. The embryologic basis for the malformation is a failure of development of the connection of the common pulmonary vein with the left atrium, and consequently, an anomalous union occurs between the pulmonary vein plexus of the developing lung buds and one of several systemic venous structures. Three main anatomic types of connection have been described: supracardiac, cardiac, and infracardiac (also called infradiaphragmatic). In about 45% of the patients, pulmonary venous return to the heart proceeds from the confluence immediately posterior to the left atrium via a left vertical venous trunk that joins the left innominate vein, which joins the right superior vena cava in normal fashion (supracardiac). In about 25% the anomalous drainage pathway descends below the diaphragm, usually to connect with the ductus venosus, and the pulmonary venous drainage eventually returns to the heart via the inferior vena cava (infracardiac). In the cardiac type, the pulmonary veins may be connected directly to the right atrium or the coronary sinus. Occasionally, veins from different lung lobes drain into different parts of the venous system (mixed connections).

The physiological and clinical features of one important subgroup of infants with total anomalous pulmonary venous connection are dictated by pulmonary venous obstruction at some level in the pulmonary venous drainage pathway. In the infradiaphragmatic type, severe obstruction to pulmonary venous return is invariable. Obstruction may result from the length and narrowness of the common trunk, compression in the esophageal hiatus of the diaphragm, or more often from the constriction that normally occurs in the ductus venosus and the resistance that the total pulmonary venous return faces when it must pass through the portal-hepatic circulation. Supracardiac drainage pathways also may manifest pulmonary venous obstruction, but this occurs less frequently. The site of obstruction may be a localized intrinsic constriction, but more frequently it occurs where the left vertical vein is compressed as it passes between the left pulmonary artery anteriorly and the left bronchus posteriorly, rather than passing anterior to the pulmonary artery. Obstruction may also occur with other types of anomalous connection.

Associated intracardiac anomalies have been described in up to 30% of patients with total anomalous pulmonary venous connection. These anomalies are usually complex lesions such as common AV canal or transposition or single-ventricle complexes and are most often associated with heterotaxy syndrome (right or left atrial isomerism).

Hemodynamics

All pulmonary venous blood returns to the right atrium, where it mixes with the systemic venous return. A variable proportion then passes to the systemic circulation through a stretched patent foramen ovale into the left atrium, ventricle, and aorta; the remainder passes to the pulmonary circulation through the tricuspid valve into the right ventricle and pulmonary artery. Systemic arterial desaturation is present as a result of the obligatory right-to-left shunting of blood at the atrial level, although, rarely, streaming of pulmonary venous blood into the left atrium gives near-normal aortic saturations. The arterial oxygen saturation varies widely but is rarely decreased significantly enough to impair oxygen delivery and depends on the ratio of pulmonary to systemic blood flow. Because the pulmonary venous blood joins with systemic venous blood at or before the right atrium, the oxygen saturations tend to be similar in all 4 chambers of the heart and in the 2 great arteries.

Most infants with supracardiac and cardiac types have little or no pulmonary venous obstruction and consequently have high pulmonary blood flow, various degrees of pulmonary hypertension, and relatively low pulmonary vascular resistance. These infants generally survive the first few weeks and months of life but may succumb to severe congestive heart failure during the first year of life unless surgically corrected. All infants with the infradiaphragmatic type and about one third of the infants with the other types manifest severe pulmonary venous obstruction and so have severe pulmonary hypertension, restricted pulmonary blood flow, pulmonary venous engorgement, interstitial pulmonary edema, and severe hypoxemia. Pulmonary artery pressures often exceed systemic pressures, and death is common in the first weeks of life if the disorder is not corrected. In all types of total anomalous pulmonary venous connection, the pressures in the right atrium are invariably higher than those in the left atrium, and occasionally pulmonary venous obstruction may result from restriction of flow across the foramen ovale.

Clinical Features

About 80% to 90% of all patients manifest tachypnea, congestive heart failure, and failure to thrive early in infancy. In the group without pulmonary obstruction, cyanosis may be minimal, but cyanosis becomes more significant as congestive heart failure progresses. In the newborn period, the heart is hyperdynamic, but heart sounds are normal; murmurs are only rarely heard. If diagnosis is delayed, the auscultatory findings change. A quadruple gallop rhythm frequently develops. A soft ejection systolic murmur is present along the left sternal border, and a mid-diastolic inflow rumble is usually heard at the lower left sternal border and apex.

In infants with the obstructed form of total anomalous pulmonary venous drainage, there is very early onset of severe dyspnea. The clinical picture is that of rapidly progressive dyspnea, pulmonary edema, intense cyanosis, and right heart failure. The second heart sound is loud and narrowly split, and a gallop rhythm may be heard. Murmurs are not prominent, but a soft blowing systolic murmur of tricuspid regurgitation may be heard at the lower left sternal border.

In the unobstructed group, the roentgenographic examination shows marked cardiac enlargement with pulmonary vascular engorgement. In the supracardiac type, a pathognomonic configuration termed “figure of eight” or “snowman” may be recognized beyond infancy; this silhouette is formed by the dilated left vertical vein, innominate vein, and right superior vena cava sitting astride the dilated heart.

A characteristic chest roentgenogram is present in those infants with pulmonary venous obstruction. The heart is normal or slightly enlarged, and the lung fields show a diffuse, hazy reticulated pattern superficially resembling the ground-glass appearance seen in the respiratory distress syndrome. Because of this and the lack of diagnostic murmurs, one is likely to misdiagnose these patients as having some form of diffuse interstitial pneumonitis if one relies on the roentgenogram alone. Early 2-dimensional echocardiographic diagnosis of a normal versus an abnormal heart is critical, especially if the apparent lung disease is not improving.

The electrocardiogram shows right ventricular hypertrophy and commonly also right atrial hypertrophy. The hypertrophy is often in excess of the normal right ventricular dominance at birth, as demonstrated by a qR complex in the right precordial leads, poor left forces, and the lack of inversion of the T waves over the first few days of life.

Two-dimensional echocardiography can establish the diagnosis and anatomy subtype of pulmonary venous connection with a high degree of sensitivity and specificity particularly in infants who have atrial situs solitus, unifocal rather than mixed pulmonary venous connections, and no evidence of other major congenital defects. It is thus critical that all infants with severe respiratory distress and cyanosis at birth undergo echocardiography early in their course, particularly if extracorporeal membrane oxygenation (ECMO) is being considered. Cardiac catheterization with angiography in these critically ill infants, no matter how carefully executed, may make them even more ill and is of little diagnostic value.

Treatment

For the severely obstructed group, rapid clinical deterioration and early death are invariable without surgical treatment. Aggressive treatment of hypoxemia and metabolic acidemia should be instituted, diuretics given, and continuous positive airway pressure with oxygen supplementation should be provided while preparations are made for surgical correction with cardiopulmonary bypass.

With all types of single connections, the aim of surgical correction is to reincorporate the common pulmonary vein into the left atrium. Because this chamber may be small, correction is carried out with a wide parallel incision between the posterior aspect of the atria and the anterior wall of the common pulmonary vein as the heart is lifted out of the pericardium. The interatrial septum may be replaced to the right of the anastomosis to enlarge the functional left atrium. The anomalous connection is simply ligated and divided.

In the unobstructed type, corrective surgery dramatically restores the normal circulatory pathways with a modest surgical risk of 5% or less under the best circumstances. When severe pulmonary venous obstruction is present, particularly for the infradiaphragmatic type, the surgical mortality has been higher, but prompt referral, aggressive management of metabolic acidemia, and early emergency surgery have had increasing success, with excellent long-term results. However, it is important to note that early (2 to 4 months) postoperative pulmonary venous obstructions have been observed in about 10% of these patients. These obstructions result either from an anastomotic stricture or from a particularly malignant form of diffuse pulmonary venous fibrosis at the venous ostia or within the lobar veins. The prognosis in the latter group of patients is very poor.187-190

Hypoplastic Left Heart Syndrome

The term hypoplastic left heart syndrome describes a group of malformations characterized by marked underdevelopment of the entire left side of the heart. The right side of the heart is dilated and hypertrophied and supports both pulmonary and systemic circulations through a patent ductus arteriosus. The specific anatomic abnormalities include underdevelopment of the left atrium and ventricle, stenosis or atresia of the aortic or mitral orifices, and marked hypoplasia of the ascending aorta. Most commonly, aortic and mitral atresia coexist, and the left ventricular cavity is minute or completely obliterated. Rarely, mitral atresia is present associated with a ventricular septal defect. Hypoplastic left heart syndrome accounted for nearly 25% of cardiac deaths in the first year of life (New England Regional Infant Cardiac Registry).

Hemodynamics

The essential hemodynamic abnormality is the absence or gross inadequacy of left ventricular function. Pulmonary venous blood passes from left to right atrium via the patent foramen ovale, and this interatrial communication is often small and restrictive to blood flow, causing severe left atrial and pulmonary venous hypertension. The ventricular septum is almost always intact. The right ventricle functions as the systemic ventricle as well as the pulmonary ventricle by delivering blood into the aorta through the widely patent ductus arteriosus. The pulmonary vascular resistance must be high to provide for this systemic function of the right ventricle. Furthermore, as the ductus arteriosus constricts intermittently, there is intermittent restriction to systemic blood flow.

In the rare condition of mitral atresia with ventricular septal defect, all the pulmonary venous blood passes through a foramen ovale to mix with systemic venous return. Blood then enters the enlarged right ventricle from which it passes into the pulmonary artery and, through a ventricular septal defect, into the hypoplastic left ventricle and the aorta. If the foramen ovale permits a large left-to-right shunt, these infants initially do quite well but then go into congestive heart failure because of a torrential pulmonary blood flow.

Clinical Features

Most infants with hypoplastic left heart complex are acutely ill, with signs of congestive heart failure within the first days or weeks after birth; those with aortic atresia succumb usually within the first few days after birth.

There are signs and symptoms of severe right-sided and left-sided heart failure: cyanosis of varying degree, and often a characteristic grayish pallor and poor peripheral pulses, which contrast with hyperdynamic cardiac pulsations. Characteristically, the peripheral pulses may diminish from time to time and then reappear, presumably related to episodes of constriction of the ductus arteriosus. The major hemodynamic abnormalities are pulmonary venous hypertension and inadequate maintenance of the systemic circulation. Murmurs are not prominent, but a short soft midsystolic murmur and mid-diastolic rumble may be present. The second heart sound is single, heard loudest at the upper left sternal border, and is accentuated until clinical deterioration with gross right heart failure is advanced.

The roentgenogram shortly after birth may show only slight cardiac enlargement, but with clinical deterioration, striking generalized cardiac enlargement and moderately prominent pulmonary vascular markings appear. Pulmonary venous obstruction may be indicated by hazy lung markings.

The electrocardiogram at birth may show normal right ventricular dominance, but if the infant survives a few days, right atrial and right ventricular hypertrophy are usual. Left-sided forces are often decreased, as evidenced by the absence of a septal q wave even out to V7 and V8 and only a small r wave in V5 and V6.

The 2-dimensional echocardiogram is diagnostic by imaging a hypoplastic ascending aorta, atresia or marked stenosis of the mitral and aortic orifices, and an obliterated or minute posterior left ventricle in conjunction with a dilated, large anterior right ventricle and large patent ductus arteriosus. These findings together with the clinical picture obviate the need for any additional invasive diagnostic studies.

Treatment

Supportive therapy directed at congestive heart failure, hypoxemia, and metabolic acidemia is of only limited benefit, and survival beyond the first week or 10 days of life is rare in the absence of maintenance of ductus patency with PGE1. Although the anatomic and functional abnormalities in hypoplastic left heart syndrome are formidable, 3 different management programs are being pursued in some centers. Most often an innovative surgical intervention (Norwood procedure) has been applied to the available structures to salvage a physiologically effective circulation by a 3-stage operative approach. Ductus closure, the immediate cause of rapid circulatory collapse and death in these neonates, is modified by a PGE1 infusion to maintain a widely patent ductus arteriosus. Surgical approaches and subsequent management is reviewed in Chapter 498.

The second approach consists of neonatal orthotopic cardiac transplantation. Although there are major difficulties related to shortage of donor hearts and the uncertainty about the long-term effects of immunosuppression therapy, excellent short-term results have been obtained with a low operative mortality (under 10%) in a few institutions. While the child is awaiting transplantation, the ductus arteriosus may be kept open by a stent.

More recently, a third hybrid approach has been practiced. The ductus arteriosus is kept open with a stent, and the surgeon bands the right and left branch pulmonary arteries. This procedure is much less stressful for a sick neonate and has low mortality. Then several months later the stent is removed, the main pulmonary artery is anastomosed to the ascending aorta as in a first stage Norwood, the right ventricle and the pulmonary artery are connected, and a Glenn procedure is done. Some months later the Fontan operation is completed. In this procedure,a high-mortality first stage of the usual Norwood procedure done in very sick, small infants is replaced with a more complicated second stage. It is too early to assess which is better.191-193

Single Ventricle

A single-ventricle (or univentricular) malformation is diagnosed when there is one ventricular chamber that receives both the mitral and tricuspid orifices or a common AV orifice. About 70% to 80% of single-ventricle malformations are derived from an l-bulboventricular loop (as opposed to the normal d-looping) and manifest bulboventricular inversion. These hearts have a single right-sided, morphologically left, ventricle with absence of the inflow portion of the right ventricle. There is persistence of a rudimentary anterior and left-sided right ventricular outflow chamber that communicates proximally with the single ventricle through a ventricular septal defect (persistent bulboventricular foramen) and distally with an l-transposed aorta. The pulmonary artery is posterior and arises from the single ventricle. Stenosis or atresia of the pulmonary outflow tract is also common, as is coarctation of the aorta, although they do not coexist—as in all congenital heart lesions, one or the other outflow tract may be obstructed, but almost never both. Subaortic stenosis as a result of a decrease in size of the bulboventricular orifice is relatively common and may occur after the pulmonary artery has been banded. Complex associated anomalies are usual, and they include dextrocardia, right atrial isomerism, common atrioventricular canal, and total anomalous pulmonary venous connection.

The term common ventricle has been used to distinguish a rare type of single-ventricle heart that has a well-developed right as well as left ventricular inflow tract; in such a heart the univentricular chamber represents essentially a huge ventricular septal defect.

Hemodynamics

The hemodynamics and clinical picture vary, depending on the pulmonary blood flow and the associated intracardiac malformations. Some degree of systemic arterial desaturation is always present because of mixing of the pulmonary and systemic venous blood in the single ventricle or, in some, an associated common atrium. With significant pulmonary stenosis or atresia, cyanosis may be severe, the heart size small, and the pulmonary vascular markings diminished. In contrast, when there is no pulmonary stenosis, the clinical and hemodynamic findings are dictated by the relationship between pulmonary and systemic vascular resistances and blood flows. In the infant, and in the older child when pulmonary vascular resistance is low, there will be torrential pulmonary blood flow with marked cardiomegaly and severe congestive heart failure. In the surviving child, increasing pulmonary vascular disease may moderate the excessive flow to the lungs.

Clinical Features

With severe pulmonary stenosis, the systolic ejection murmur is usually loud; with pulmonary atresia, no murmurs may be heard except in the presence of atrioventricular valve insufficiency. An aortic ejection click may be heard; the second heart sound is usually single and loud. With markedly increased pulmonary blood flow, cyanosis may be quite mild, the systolic ejection murmur pansystolic, the second heart sound loud and narrowly split, and a third heart sound and short mid-diastolic rumble are often present.

The chest roentgenogram establishes the extent of cardiomegaly and pulmonary blood flow and the shape of the heart silhouette—straightened left heart border is often characteristic and should suggest the diagnosis of a single left ventricle with small rudimentary right ventricular outflow tract associated with l-malposition of the great arteries.

The electrocardiogram is nonspecific, presenting either right or left axis deviation and a precordial QRS pattern suggesting either right, combined ventricular, or left ventricular dominance. Large unchanging equiphasic or negative complexes across the entire precordium should raise a suspicion of single-ventricle malformation.

Two-dimensional echocardiography can establish the diagnosis of single-ventricle complex and provide additional anatomic details such as the presence of 2 atrioventricular orifices or 1 large common orifice, the orientation of the rudimentary outflow chamber, pulmonary outflow tract stenosis, and possibly anomalous pulmonary venous connections.

Cardiac Catheterization

Cardiac catheterization and angiography may be helpful in differentiating certain particularly complex malformations such as “criss-cross” or “upstairs-downstairs” hearts and for identifying pulmonary or subpulmonary stenosis, measuring the pulmonary vascular resistance, establishing the anatomic course of the rudimentary small outlet chamber and the spatial relationships and connections of the cardiac chambers and great vessels, and the details of abnormal pulmonary or systemic venous connections. Magnetic resonance imaging is also helpful for assessing complex anatomic details.

Treatment

The management of single ventricle is discussed in detail in Chapter 498. The clinical course and prognosis are often grave, but palliation and long-term salvage have been effected for infants with decreased pulmonary blood flow by surgically creating either systemic-pulmonary or cavopulmonary anastomoses and for infants with increased pulmonary blood flow by pulmonary artery banding, with subsequent progression to the modified Fontan circulation. If there is subaortic stenosis, the proximal pulmonary arterial trunk can be anastomosed to the aorta (Damus-Kaye-Stansel procedure). Occasionally, a prosthetic septum has been successfully placed in some forms of single-ventricle hearts. These formidable procedures have been significantly aided by the recent recognition in such hearts of abnormal disposition of the cardiac specialized conduction tissue arising from an anterior rather than a normal posterior atrioventricular node and coursing as the bundle of His astride the anterior (conal) septum.194-199

Truncus Arteriosus

Truncus arteriosus, constituting 2% of all congenital heart lesions, is characterized by the emergence of only a single arterial trunk from the ventricular chambers, and this vessel supplies the coronary, pulmonary, and systemic circulations proximal to the aortic arch. A truncal valve, usually with 3 or 4 leaflets, overrides a ventricular septal defect, which is always present. The pulmonary arteries generally arise as a single vessel or as 2 separate vessels from the posterior or lateral wall of the truncus. Truncus arteriosus must not be confused with the relatively common lesion tetralogy of Fallot with pulmonary atresia, also characterized by a single large vessel—the aorta—that arises from the heart. In tetralogy of Fallot with pulmonary atresia, however, there is a hypoplastic or atretic pulmonary artery attached to the right ventricular outflow region, and the lungs are supplied with blood by pulmonary arteries arising from a ductus arteriosus or from major aortopulmonary collateral vessels usually arising from the thoracic descending aorta. Similar to these patients, though, a large percentage of infants with truncus arteriosus have partial deletion of chromosome 22. About 30% to 50% have a right aortic arch. Rarely, interrupted aortic arch is present with the descending aorta being supplied from the main pulmonary artery via the ductus arteriosus.

Hemodynamics

The right and left ventricles eject blood at systemic pressure into the common arterial trunk; thus, the coronary arteries, pulmonary arteries, and aorta receive a mixture of venous and oxygenated blood at systemic pressure. The pulmonary blood flow is markedly increased in infancy because there are usually primary pulmonary artery branches of adequate size and the pulmonary vascular resistance is initially not greatly increased. Consequently, cyanosis is minimal, and the hemodynamics as well as the clinical picture are those of a large left-to-right shunt. The pulmonary circulation may be restricted in a few patients by the development of pulmonary vascular obstructive disease or rarely by hypoplastic or stenotic pulmonary arteries arising from the truncus; in 16% of patients, one pulmonary artery is absent.

Clinical Features

Symptoms usually appear in the first weeks or months of life and are consistent with a large left-to-right shunt: left heart failure, dyspnea, wheezing, frequent respiratory infections, and poor physical development. Failure to thrive is universal. In the infant, cyanosis is often not apparent or is minimal at rest because the pulmonary blood flow is so high. The heart is hyperdynamic, and peripheral pulses are prominent or bounding. The second heart sound is loud and single because of the single set of semilunar valves. A prominent systolic ejection click is heard very commonly at the lower and middle left sternal border. A harsh systolic murmur may best be heard along the middle left sternal border, and a continuous murmur is heard at the base or lateral chest wall in older infants and children. In newborn or young infants, particularly those with marked congestive heart failure, only a systolic murmur may be heard, similar to the findings in some newborn infants with a large patent ductus arteriosus. Severe truncal valve regurgitation may be suspected from a prominent to-and-fro quality in the murmur. Truncal valve stenosis occurs rarely.

If pulmonary blood flow is restricted, either by high pulmonary vascular resistance or by stenotic or hypoplastic pulmonary arteries, cyanosis is more severe, congestive heart failure is unusual, only a minimal systolic murmur of short duration and low intensity is heard, and there may be a faint continuous bruit representing bronchial pulmonary collateral flow.

Roentgenographic findings also depend on the size of the pulmonary arteries and the pulmonary blood flow pattern. In most infants there is considerable cardiac enlargement, with increased pulmonary vascular markings. When pulmonary blood flow is decreased, both heart size and pulmonary vascular markings are less prominent. A right aortic arch is common (30% to 50%), and the hilar origin of the pulmonary artery may appear superiorly displaced.

The electrocardiogram demonstrates right ventricular or combined ventricular hypertrophy.

Two-dimensional echocardiography establishes the diagnosis by demonstrating a large, single arterial vessel overriding the ventricular septum and identifying a main or primary branch pulmonary artery arising directly from this common trunk. The ductus arteriosus is often absent except with an interrupted aortic arch. Cardiac catheterization is rarely indicated in the young infant, but, if performed, selective angiography reveals the common trunk arising from the heart and the origin of the pulmonary arteries from the truncus.

Treatment

The prognosis is variable, depending to a considerable degree on the pulmonary blood flow pattern; about 75% of infants if unoperated die within the first 3 to 12 months from heart failure. Corrective surgery has been developed and widely applied, provided the patient is free from significant pulmonary vascular disease, which often develops by 3 to 4 months of age. The ventricular septal defect is closed to leave the aorta arising from the left ventricle, the pulmonary arteries are removed from their common truncus origin, and a valved conduit is placed from the free right ventricular wall to the pulmonary arteries to form a new right ventricular outflow tract (Rastelli procedure). At present, the lowest operative mortality (under 10%) and the highest long-term yield of good results are achieved by corrective surgery done under 3 months of age. The child will have the initial small conduit changed to a larger size after 3 to 7 years and will have to have the second conduit changed to a larger size after 5 to 10 years. Truncal valve regurgitation, modest in about 25% but severe in about 5% to 10%, remains an important factor in late mortality; sometimes truncal valve replacement is needed.200-204

Because a newborn with cyanotic heart disease can deteriorate rapidly, usually when the ductus arteriosus closes, it is essential to make an early diagnosis. This is particularly important when the baby is born in an outlying hospital where expert consultation and pediatric echocardiography are not available. The primary differential diagnosis is between lung and heart disease, the former often being treatable locally and the latter requiring rapid transport to a regional cardiac center.

The tools needed for diagnosis are primarily the physical examination, aided by chest roentgenogram and pulse oximetry that are available in almost all hospitals, and in some hospitals by measured arterial oxygen tension. The use of pulse oximetry needs further discussion. At best, oximetry diagnoses decreased arterial oxygen saturation. It does not diagnose the cause of the cyanosis, and it is not needed if cyanosis is severe except perhaps to quantify the degree of arterial oxygen desaturation. For mild desaturation, the limitations of oximetry must be appreciated. Different instruments may differ by 5% to 10% in saturation estimates, and saturations obtained with increased ambient light, patient movement, or markedly decreased peripheral perfusion can also be erroneous. At the time of birth, before lung expansion is complete, oxygen saturation may be as low as 60% in normal infants, but rises to above 90% by 15 minutes after birth. Within the first 24 hours, preductal may be higher than postductal saturation because of a small right-to-left ductus shunt due to pulmonary arterial hypertension, but this difference normally disappears after 24 hours. Saturations are 4% to 8% lower during quiet sleeping than being awake and alert. At sea level, healthy infants have saturations with mean values found in several studies of 93.9% to 97.6%. Only 5% to 6% were below 92%, and almost all of these became normal within 3 days. At high altitude, for example 3100 m at Leadville, Colorado, saturations in healthy babies vary from 80% to 88% at a week of age to 86% to 91% at 4 months. For all these reasons, oximetry is not a valuable diagnostic test, but it may serve to draw attention to other aspects of the patient.

Functional obstruction occurs in anomalies with bidirectional shunts and a huge pulmonary blood flow. Hyperactive hearts, usually loud murmurs, and only mild cyanosis characterize these anomalies. However, during the neonatal period, because pulmonary vascular resistance is still relatively high, cyanosis is more marked, precordial pulsation is only slightly increased and lung function is fairly normal. (See Chapter 483.) As pulmonary vscular resistance decreases, pulmonary blood flow is increased by the left-to-right shunt, the precordium becomes hyperactive, cyanosis decreases, but lung function deteriorates.

Patients who are cyanotic and have loud cardiac murmurs are very likely to have congenital heart disease rather than lung disease, although occasionally patients with lung disease and pulmonary arterial hypertension have a loud murmur of tricuspid regurgitation. Unfortunately, not all forms of congenital heart disease have characteristic murmurs, and these are indicated by an asterisk against the diagnoses in Figure 484-1. As a rule, however, the diagnosis of some form of congenital heart disease is easy, even if the specific anomaly is unclear.205-221

A heart abnormally situated in the thorax is said to show malposition. Such hearts often have abnormalities of chamber localization and great artery attachments as well as septal defects, valve anomalies, and outflow obstructions. Describing the basic structure of such a complex heart requires description of 3 cardiac segments (atria, ventricles, and great arteries) and should include not only positional interrelationships but also connections of ventricles to atria and great arteries.

Situs and Atria

The right and left atria may be regarded as extensions of the systemic and pulmonary veins, respectively, so that the body situs indicates the positions of the atria. Body situs is determined by certain organs that are normally asymmetric. The normal body configuration, situs solitus, is characterized by a right lung with 3 lobes and an eparterial bronchus, a left lung with 2 lobes and a hyparterial bronchus, asymmetric tracheobronchial branching, a liver with a major lobe on the right, a left-sided stomach and spleen, right-sided venae cavae, morphologically distinct atria, and a specific orderly arrangement of the gastrointestinal tract. Situs inversus is characterized by a mirror-image configuration of the asymmetric organs, including the gastrointestinal tract. In addition to these 2 asymmetric forms of situs, 2 roughly symmetric body configurations have been found with right and left atrial isomerism. Right atrial isomerism is characterized by bilateral right-sidedness, with bilateral 3-lobed lungs, each with a typical right bronchial branching pattern, a horizontal liver with equal-sized lobes, and bilateral morphologic right atria, each with a sinoatrial node. The spleen is usually absent (asplenia), and this may also be regarded as a feature of bilateral right-sidedness. In contrast, left atrial isomerism is characterized by bilateral left-sidedness involving lungs, bronchi, and the atria. There are usually multiple (2 to 30), roughly equal-sized spleens with a total mass equal to that of a normal-sized spleen clustered together on both sides of the dorsal mesogastrium (polysplenia). This is in contrast to accessory spleens, which are small isolated splenic masses in addition to a normal spleen. Malrotations of the bowel are common in both asplenia and polysplenia. Right and left atrial isomerism replace the terms asplenia and polysplenia, respectively, because splenic morphology and isomerism do not always match. In general, organ symmetry is more variable with left than with right isomerism.

Ventricles

The primitive cardiac tube normally bends to the right and forms a d-loop, so that the anatomic right ventricle lies to the right of the anatomic left ventricle. Such a loop is appropriate or concordant for a situs solitus individual; that is, the right atrium connects to the right ventricle, and the left atrium connects to the left ventricle. Conversely, an l-loop is concordant for a situs inversus individual. Occasionally a discordant loop forms (l-loop in situs solitus or d-loop in situs inversus); the anatomic right atrium connects to the anatomic left ventricle, and anatomic left atrium connects to anatomic right ventricle.

Great Arteries

Great arteries may be described by their ventricular connections and positional interrelationships. Ventricular connections may be normal (pulmonary artery from right ventricle, aorta from left ventricle), double-outlet right or left ventricle (DORV or DOLV, respectively), or transposition (aorta from right ventricle, pulmonary artery from left ventricle). The positional interrelationships may be described as d (dextro), where the aortic valve is to the right of the pulmonary artery; l (levo), where the aortic valve is to the left; or o (ortho), where the aorta is directly in front of the pulmonary artery—these terms are not to be confused with d-loops and l-loops. Usually great-artery interrelationships reflect ventricular interrelationships; however, there are enough exceptions that description of both segments is preferable.

The right ventricular infundibulum (or conus) is usually the most anterior cardiac structure and connects with the anterior great artery. Accordingly, normally related great arteries usually have an anterior pulmonary artery, transpositions have an anterior aorta, and double-outlets tend to have side-by-side vessels. Vessels arising from the left ventricle almost always lack a conus, and so their valves are more caudad than are those arising from the right ventricle.

Discordant loops (solitus/l-loop or inversus/d-loop) are almost always associated with transposition of the great arteries. The sequential arrangement of chambers and great arteries in these patients is such that the flow is potentially normal, and so these lesions have been called (physiologically) corrected transposition of the great arteries. Any abnormal circulation in these hearts is the result of associated abnormalities such as septal defects or atrioventricular (AV) valve stenoses or regurgitation, one or more of which occur in nearly all. The conduction pathways are also abnormal and may produce various degrees of AV block.

A simplified nomenclature for describing complex hearts (after van Praagh and colleagues) is as follows:

Situs

• Solitus
• Inversus
• Right atrial isomerism
• Left atrial isomerism

Ventricles

• d-Loop: morphologic RV to right of morphologic LV
• l-Loop: morphologic LV to right of morphologic RV
• d- or l-Single-ventricle: outlets of both atria to a large primitive ventricle with small outlet chamber that has no AV valve; as the outflow chamber is the RV outflow, its position determines d or l designation

Great arteries

• d: Aortic valve to right of pulmonic
• l: Aortic valve to left of pulmonic
• o: Aortic valve directly anterior
• Normal: PA from RV, Ao from LV
• DORV: PA and Ao from RV
• DOLV: PA and Ao from LV
• Trans: Ao from RV, PA from LV
• Malposition: unusual arrangement of vessels not conforming to above

Hence, segmental sets may be described as follows: solitus/d-loop/d-trans is the usual transposition of the great arteries in situs solitus; inversus/d-loop/d-trans is corrected transposition of the great arteries in situs inversus; right atrial isomerism/d-single/d-trans is single ventricle with aorta from small outlet chamber and pulmonary artery from large single ventricle in right atrial isomerism. Additional defects (eg, septal defects, stenoses, anomalous veins) must be described separately.

Cardiac Position

A heart predominantly in the left hemithorax is termed levocardia and is normal for situs solitus. If the heart is mainly in the right hemithorax, it is referred to as dextrocardia, the normal for situs inversus. Cardiac position within the thorax may be influenced by external forces (eg, a hypoplastic right lung or left diaphragmatic eventration may displace the heart to the right). In the absence of such external factors, cardiac position is most closely related to concordance or discordance of the bulboventricular loop. Concordant loops nearly always have normal ventricular position for that situs—that is, left-sided heart for situs solitus and right-sided heart for situs inversus. Exceptions are few and tend to be accompanied by less severe, if any, cardiac abnormalities. Discordant loops in situs solitus or situs inversus and (because atrial symmetry precludes concordance) all loops in atrial isomerisms have variable cardiac positions; for example, an l-loop in situs solitus (or atrial isomerism) can have a right-sided, left-sided, or midline heart. Similarly, a d-loop in situs inversus or atrial isomerism can have any position.222-229

These anomalies arise from abnormal persistence and dissolution of all or some of the paired embryonic aortic arches that connect the embryonic truncus arteriosus to the paired dorsal aortas. Abnormal development of these arteries may produce no symptoms (aberrant right subclavian artery, right aortic arch) or may press on the esophagus or trachea and cause dysphagia and airway obstruction. Therefore, diagnosis can usually be made by examining the characteristic indentations that the abnormal arteries make on the barium-filled esophagus or the trachea. Confirmation by echocardiography, computerized tomography, or magnetic resonance imaging has replaced aortography. Physical examination of the heart and the electrocardiogram are usually normal.

Infants with severe obstructions are very ill with vomiting, choking, and often dysphagia, so that feeding and weight gain are poor. Wheezing and stridor, usually inspiratory, are often prominent and made worse by feeding. Frequently, these infants hyperextend their heads to reduce tracheal compression. Episodes of cyanosis, apnea, or unconsciousness occur. Most of these infants develop symptoms below 3 months of age. Less severe obstruction may present with recurrent respiratory infections.

The most common anomaly is an aberrant right subclavian artery. When the proximal rather than the distal part of the right fourth arch is absorbed, the right subclavian artery runs posteriorly from the descending thoracic aorta to reach the right arm, passing obliquely up and to the right behind the esophagus and indenting it posteriorly. This anomaly so rarely causes symptoms that even if it is found, some other cause of esophageal or respiratory symptoms should be sought. On the other hand, some children with dysphagia are cured when the artery is repositioned. In adults, many of these aberrant arteries develop aneurysms at their origins, and these can rupture.

If the distal fourth arch disappears on the left rather than on the right, there will be a right aortic arch and a mirror-image arrangement of arteries to the arms and head. This is not a cause of symptoms, but the prominent roentgenographic shadow that the arch casts on the right side of the mediastinum may be mistaken for enlarged nodes or a tumor. A right aortic arch is found in about 25% of patients with the tetralogy of Fallot and about 50% with truncus arteriosus.

Most anomalies that cause serious symptoms encircle the esophagus and trachea to form a vascular ring. The most common of these is the double aortic arch, which can result from failure of absorption of any part of the embryonic fourth arches. The right and left arches indent the right and left sides of the trachea and the esophagus, and the right arch indents the esophagus posteriorly as it passes to the left behind the esophagus to join the left arch, usually the smaller arch, and form the descending aorta. Sometimes the descending aorta is right sided, and the left arch is retroesophageal. Division of one of the arches, usually the smaller posterior one, opens the constricting ring and is curative; this can be done by open or thoracoscopic surgery. However, deformity of the tracheobronchial tree may cause residual postoperative airway problems.

Almost as common is the right aortic arch that becomes a constricting ring because of a retroesophageal left-sided patent ductus arteriosus or ligamentum arteriosum. The combination produces indentations on the esophagus and trachea similar to those that occur with a double arch. Division of the ductus or ligamentum is curative. Note that infants with any of these aortic arch anomalies may have a complete or partial DiGeorge syndrome, associated with a deletion in chromosome 22q11.

Occasionally a carotid or innominate artery compresses the anterior margin of the trachea. This may show up on roentgenograms of the tracheal air column or on a tracheogram, but the esophagram is normal. If needed, the compressing artery can be displaced anteriorly at surgery.

Although not a vascular ring, the anomalous left pulmonary artery also causes airway obstruction. The left pulmonary artery arises from the right pulmonary artery and passes between the esophagus and trachea, compressing the trachea and the right main bronchus. It is the only important vascular anomaly to indent only the anterior edge of the esophagus. The infants may have cough, wheezing, stridor, and episodes of choking, cyanosis, or apnea, but dysphagia is rare. There may be collapse or hyperinflation of part of the right lung. Associated cardiovascular anomalies are common. Diagnosis is made by a combination of esophagrams, bronchoscopy, and angiography. Surgical reattachment of the left pulmonary artery to the main pulmonary artery relieves the obstruction, but tracheal stenosis often leads to suboptimal results.230-242

Anomalous Origin of Left Coronary Artery

The left coronary artery arises from the pulmonary artery, and the right coronary artery arises normally from the anterior aortic sinus. During fetal life, with similar pulmonary arterial and aortic pressures and saturations, myocardial perfusion and oxygenation are normal. However, after birth, pulmonary arterial pressure decreases, and blood flows from the right coronary artery through collateral vessels into the left coronary artery and then into the pulmonary artery. Thus, a small left-to-right shunt is produced, and blood destined for the myocardium is diverted to the pulmonary artery through these channels. Usually the anterolateral wall of the left ventricle is involved.

Generally patients present with myocardial failure from ischemia or even a myocardial infarct between 2 weeks and 6 months of age. Episodes of restlessness and crying, as if in pain, associated with pallor and sweating have been described in infants with this anomaly, but poor feeding, tachypnea, and respiratory symptoms related to left ventricular failure are more usual. Severe cardiomegaly is the rule, and mitral regurgitant murmurs often result from dilatation of the mitral valve ring or papillary muscle infarction. Prominent third and fourth heart sounds are common. The electrocardiogram shows an anterolateral infarct pattern, with broad, deep Q waves in leads I, aVL, and the left precordium, often associated with persistent S-T segment and T-wave changes in these leads. Increased left ventricular forces are usual. The chest x-ray shows cardiomegaly and usually pulmonary venous congestion. Other lesions that present with similar findings include endocardial fibroelastosis, myocarditis, and glycogen storage disease involving the heart. Because anomalous origin of the left coronary artery is treatable, this diagnosis must be considered when there is unexplained left ventricular failure in infancy; it can be suspected on 2-dimensional echocardiography but often must be confirmed by cardiac catheterization and angiocardiography. Treatment consists of reimplanting the left coronary artery into the aorta, by connecting it to the aorta by a tunnel that passes through the pulmonary artery, or by aortocoronary bypass grafting. If these are not feasible, ligating the anomalous left coronary artery, if there is a left-to-right shunt from the coronary artery into the pulmonary artery, prevents runoff and thereby permits better perfusion of the surviving myocardium through the collateral vessels. Treatment usually causes improvement in any mitral regurgitation, but rarely repair of the mitral valve may be needed.

Anomalous Aortic Origin of Coronary Arteries

Occasionally the left coronary artery arises from the right aortic sinus of Valsalva, or the right coronary artery arises from the left aortic sinus of Valsalva. The anomalously arising artery may reach its territory of supply by passing between the aorta and the pulmonary artery. Patients with this anomaly have episodes of chest pain, syncope, or even sudden death, which unfortunately may be the first abnormal event. Almost invariably these symptoms occur during or just after strenuous exercise. The anomaly is almost never familial.

The anomaly cannot be diagnosed clinically. However, unexplained chest pain or syncope on exercise require screening by echocardiography and, even if this is normal, by coronary angiography, computerized tomography, or magnetic resonance imaging. The anomalous artery can be implanted surgically into its correct sinus to prevent further danger. An anomalous left coronary artery has such a high risk that it should always be treated when found. An anomalous right coronary artery is less sinister, and decisions about treatment can be very difficult.

Coronary Arteriovenous Fistulas

See above.

Miscellaneous Anomalies

Some coronary arteries come off a single trunk from the aorta. Other than an increased risk if there is coronary atheroma, these patients occasionally die suddenly, most often when the single trunk passes between the aorta and pulmonary artery. The clinical presentation and diagnosis are the same as for anomalous aortic origin of the coronary arteries.

Rarely the whole coronary arterial system is hypoplastic. There may be ischemic symptoms or sudden death. Diagnosis is made by angiography. There is no specific treatment.

Sudden death has also occurred in patients with normally attached coronary arteries who, at autopsy, have had slitlike orifices of a coronary artery and in whom the first part of the coronary artery emerges tangentially rather than being perpendicular to the aortic wall.243-252