Neonatal Cardiology, 3rd Ed. Michael Artman

Chapter 6. Approach to the Cyanotic Infant

■ INTRODUCTION

■ PATHOPHYSIOLOGY OF CYANOSIS

Oxygen Delivery

Hemodynamic Categories of Cyanotic

Cardiovascular Disease

Clinical Presentation of Cyanotic Cardiovascular Disease

■ DEFECTS WITH DECREASED PULMONARY

BLOOD FLOW

Fetal Physiology

Decreased Pulmonary Blood Flow With Inflow

Obstruction

Decreased Pulmonary Blood Flow With Outflow Obstruction

Decreased Pulmonary Blood Flow With Valvar Regurgitation

■ d-TRANSPOSITION COMPLEXES

Fetal Physiology

Simple d-Transposition of the Great Arteries

d-Transposition of the Great Arteries With

Ventricular Septal Defect

Taussig-Bing Anomaly

■ PALLIATIVE PROCEDURES

Systemic-to-Pulmonary Artery Shunts

Approach to the Patient With a Functional Single Ventricle

■ SUGGESTED READINGS

■ INTRODUCTION

Cyanosis is the most common manifestation of symptomatic cardiovascular disease in the newborn infant. Moreover, cyanosis in the absence of significant respiratory distress is almost always caused by structural cardiovascular disease because pulmonary disease severe enough to cause cyanosis is usually associated with severe respiratory distress. Congenital cardiovascular defects that cause primarily cyanosis in newborn infants are reviewed in this chapter. Infants who have decreased systemic perfusion as the primary symptom, even if cyanosis is also present, are discussed in Chapter 8.

■ PATHOPHYSIOLOGY OF CYANOSIS

Oxygen Delivery

Adequate oxygen delivery to meet metabolic needs is essential for healthy survival. The amount of oxygen delivered to the tissues is dependent on systemic blood flow, hemoglobin concentration, and hemoglobin oxygen saturation (Table 6-1). At birth, oxygen consumption increases nearly threefold to meet the energy costs of breathing, feeding and digestion, and thermoregulation. Immediately after birth, systemic blood flow at least doubles, and systemic arterial oxygen saturation increases from about 75% to 95% (reviewed in Chapter 3). Thus, despite the increase in oxygen consumption, oxygen delivery increases similarly, and the reserve to extract oxygen remains large in normal infants. The fractional extraction of oxygen is about 30% so that the mixed venous saturation is about 65% to 70%. In contrast, newborn infants with cyanotic congenital heart disease cannot increase systemic arterial oxygen saturation, and, in fact, oxygen saturation often falls precipitously soon after birth. These infants are therefore at risk for inadequate systemic oxygen delivery, which, if untreated, may result in anaerobic metabolism, metabolic acidosis, and death.

TABLE 6-1. Calculation of Oxygen Delivery and Blood Flows

SOD, systemic oxygen delivery. Q_s, systemic blood flow. C_SA, oxygen content of systemic arterial blood. VO2, oxygen consumption. Csv, oxygen content of mixed systemic venous blood. Qp, pulmonary blood flow. Cpv, oxygen content of pulmonary venous blood. Cp_A, oxygen content of pulmonary arterial blood. Q_EP, effective pulmonary blood flow. C, oxygen content. c, constant describing the oxygen carrying capacity of a unit of hemoglobin (each gram of hemoglobin can carry 136 mL of oxygen per liter of blood). Hb, blood hemoglobin concentration. S, oxygen saturation of a given source of blood.

Hemodynamic Categories of Cyanotic Cardiovascular Disease

Decreased pulmonary blood flow (Table 6-2) and malposition of the aorta over the systemic venous ventricle (transposition complexes) are the two main pathophysiological mechanisms responsible for severely decreased systemic arterial saturation in newborn infants with cyanotic heart disease. In the normal postnatal circulation, all of the poorly saturated systemic venous blood is directed through the right heart structures to the pulmonary arteries; the oxygen saturations of the blood in the systemic veins and pulmonary arteries are therefore equal. This blood becomes nearly fully saturated as it takes up oxygen in the pulmonary capillary bed and returns to the heart via the pulmonary veins. Pulmonary venous blood then passes through the left heart structures to the aorta. Thus, the oxygen saturations in the pulmonary veins and systemic arteries are the same, and pulmonary blood flow is equal to systemic blood flow (Table 6-1).

TABLE 6-2. Congenital Cardiovascular Defects Presenting With Cyanosis Caused by Decreased Pulmonary Blood Flow

Anatomic level	Structural defect
Tricuspid valve	Tricuspid valve regurgitation Tricuspid valve stenosis or atresia Ebstein anomaly
Right ventricle	Hypoplastic right ventricle Tetralogy of Fallot (subpulmonic stenosis with ventricular septal defect)
Pulmonary valve	Pulmonary valve stenosis or atresia with intact ventricular septum Pulmonary valve stenosis or atresia with ventricular septal defect (± single ventricle, malposed aorta, or aortopulmonary collateral vessels) Absent pulmonary valve syndrome
Pulmonary artery	Supravalvar pulmonary artery stenosis Branch pulmonary artery stenosis

In conditions of decreased pulmonary blood flow (Table 6-2), systemic venous blood returns to the right atrium, but some of this desaturated blood does not reach the pulmonary arteries for oxygen uptake. Rather, a portion passes to the left heart structures and aorta, where it mixes with pulmonary venous blood, resulting in decreased systemic arterial saturation. In addition, a portion of pulmonary venous blood often returns to the lungs (eg, via a ductus arteriosus) and does not contribute to oxygen uptake. “Effective pulmonary blood flow” is defined as the volume of systemic venous blood delivered to the pulmonary arteries for oxygen uptake and is directly proportional to the oxygen saturation in the aorta (Table 6-1). In conditions of malposition of the aorta over the systemic venous ventricle (transposition complexes), cyanosis also occurs; in this situation, however, pulmonary blood flow is normal or even increased. For example, when the aorta is malposed over the ventricle that receives the systemic venous return (typically the right ventricle), most of the systemic venous blood is ejected into the aorta. Depending on the position of the pulmonary artery and the presence or absence of a ventricular septal defect, varying amounts of pulmonary venous blood are ejected into the aorta and pulmonary artery. In the most common defect in this category—d-transposition of the great arteries with intact ventricular septum (Figure 6-1A)—all of the pulmonary venous blood flows back to the pulmonary arteries if there is no communication between the two sides of the heart. The volume of pulmonary blood flow is normal, but it never reaches the systemic circulation—this is not compatible with survival. Survival is dependent on at least some of pulmonary venous blood entering the aorta. This must occur at the atrial level (eg, from the left atrium across the foramen ovale into the right atrium, right ventricle, and then the aorta), the arterial level (the ductus arteriosus), or both. Patency of the foramen ovale or ductus arteriosus is essential to survival. In the presence of both, left-to-right flow through the ductus arteriosus increases pulmonary blood flow so that left atrial volume and pressure increase, which in turn increases the left-to-right atrial shunt.

Transposition of the great arteries is called ventricular- arterial discordance because the ventricles connect to the wrong arteries. In simple d-transposition of the great arteries, there is atrial-ventricular concordance because the right atrium connects normally to the anatomic right ventricle through a tricuspid valve, and the left atrium connects normally to the anatomic left ventricle through a mitral valve. However, atrial-ventricular discordance can also occur. In that case, the right atrium connects via the mitral valve to the left ventricle, and the left atrium connects via the tricuspid valve to the right ventricle (Figure 6-1B). If both atrial-ventricular discordance and ventricular-arterial discordance are present together, blood flow patterns are normal. Thus, this condition is often called “corrected” transposition of the great arteries. l-transposition of the great arteries is a more appropriate term because the embryologic abnormality is failure of the primitive heart tube to rotate to a rightward (d-looped) position. Instead, rotation is to the left (l-looping). As an isolated anomaly, l-transposition of the great arteries does not cause symptoms in infants, but associated cardiovascular defects are commonly present (see following text).

Clinical Presentation of Cyanotic Cardiovascular Disease

Cyanosis is a critically important clinical finding to detect in the newborn infant. It is the primary presentation of cardiovascular disease that manifests symptomatically in the newborn infant. If cyanosis due to congenital cardiovascular disease is not recognized, the neonate may experience rapid and severe cardiovascular decompensation. Evaluation of cyanosis is discussed in Chapter 5, but the critical features of cyanotic congenital cardiovascular disease are the following:

• Systemic arterial hypoxemia is manifested clinically by central rather than peripheral cyanosis.

• Cyanosis is often not present immediately after birth, particularly in infants who have defects that cause decreased pulmonary blood flow, because the ductus arteriosus is still widely patent.

• Cyanosis is not evident until a significant amount of reduced hemoglobin is present. If an infant has a systemic arterial oxygen saturation above 85%, cyanosis may be quite difficult to detect by visual inspection. Oxygen saturation should be measured by pulse oximetry in all newborn infants as a screening test and at any time that there is concern that central cyanosis may be present.

• Oxygen saturation may differ between the upper and lower body. The ascending and descending aorta may be perfused by different ventricles if the ductus arteriosus is patent. Pulse oximetry should be performed on the right hand, which receives blood from the ascending aorta in the normal aortic arch, and on either foot, which receives blood from the descending aorta. Certain conditions are associated with different relationships in oxygen saturation between the upper and lower body; defining the relationship may be very helpful to identify the specific defect causing cyanosis (Table 6-3). It should also be remembered that, rarely, the right subclavian artery arises from the descending aorta and does not reflect ascending aorta saturation (Chapter 5).

• Infants with cyanotic heart disease are hypoxemic and thus breathe rapidly. However, they rarely have respiratory distress (ie, no retractions or nasal flaring), and arterial CO2 levels are usually decreased because of hyperventilation. Thus, these defects are rarely confused with primary lung disease.

■ DEFECTS WITH DECREASED PULMONARY BLOOD FLOW

Obstruction to blood flow within the right heart or pulmonary arteries or severe regurgitation of the tricuspid or pulmonary valve causes decreased pulmonary blood flow (Table 6-2). Obstructive defects are far more common than defects in which valvar regurgitation is the dominant problem. In all of these situations, a portion of the systemic venous blood is shunted from the right atrium through the foramen ovale to the left atrium, where it mixes with pulmonary venous blood, resulting in systemic arterial desaturation. In certain defects, a right-to-left shunt across a ventricular septal defect is also present. Because obstruction or regurgitation almost always occurs proximal to the ductus arteriosus, upper and lower body saturations are always similar in this group of defects, even if the ductus arteriosus is patent. This is a very important finding that differentiates this group of newborns from those with transposition complexes or persistent pulmonary hypertension of the newborn (Table 6-3).

FIGURE 6-1. A. Simple d-transposition of the great arteries (ventricular-arterial discordance). The immediate postnatal circulation shows pulmonary venous blood returning to the pulmonary artery and systemic venous blood returning to the aorta, causing severe cyanosis. The shunt through the foramen ovale, if present, passes in a left-to-right direction. The shunt through the ductus arteriosus is mixed, with a small right-to-left shunt in early systole and a much larger left-to-right shunt in diastole. Red arrows indicate oxygenated blood, and blue arrows indicate desaturated blood. Abbreviations: LA, left atrium; LV, anatomic left ventricle; RA, right atrium; RV, anatomic right ventricle.

FIGURE 6-1. B. l-transposition of the great arteries (atrial-ventricular and ventricular-arterial discordance). The immediate postnatal circulation shows systemic venous blood returning normally to the right atrium and then flowing to the anatomic left ventricle and pulmonary artery. Pulmonary venous blood returns to the left atrium and then flows to the anatomic right ventricle and aorta. Aortic saturation is normal, and there is a small left-to-right ductal shunt. The aorta arises anteriorly and to the left (l-loop) and ascends to the right. Red arrows indicate oxygenated blood, and blue arrows indicate desaturated blood. The abbreviations are the same as for Figure 6-1A.

Fetal Physiology

During fetal life, inflow or outflow obstruction to the right ventricle without a ventricular septal defect causes a large portion of blood that would otherwise enter the right ventricle to cross the foramen ovale into the left atrium. In the extreme case of either tricuspid atresia or pulmonary atresia with intact ventricular septum (Figure 6-2), all systemic venous return passes through the foramen ovale. Thus, the foramen ovale is extremely large in utero. Postnatally, a significant interatrial communication is usually present.

TABLE 6-3. Possible Diagnoses by Defect Groups in Newborn Infants With Upper Body Oxygen Desaturation and With Variable Lower Body Desaturation

Lower body oxygen saturation (relative to upper)	Defect groups possible	Defect groups excluded
Same	Decreased pulmonary blood flow Transposition complexes Pulmonary hypertension	None
Higher	Transposition complexes	Decreased pulmonary blood flow Pulmonary hypertension
Lower	Pulmonary hypertension	Decreased pulmonary blood flow Transposition complexes

This defect is essentially a stretched foramen ovale in which the flap does not fully close the foramen after birth. The interatrial communication is almost always nonrestrictive after birth, and systemic venous return to the left heart is unobstructed. However, in rare cases, the opening in the atrial septum is too small, and an emergency atrial septostomy is necessary to maintain systemic output.

In these conditions, the left ventricle receives much more of the combined venous return because of the increased blood flow into the left atrium across the foramen ovale. The coronary and upper body circulations receive a normal amount of combined ventricular output so that the excess output passes through the aortic arch and isthmus to the descending aorta. This enlarges the aortic isthmus so that coarctation of the aorta does not occur. This is another important finding that differentiates these defects from the transposition complexes, in which coarctation of the aorta may be present.

Flow across the foramen ovale is not increased in the group of infants with obstruction to pulmonary blood flow who have a ventricular septal defect. For example, in patients with tetralogy of Fallot, venous return passes normally to the right ventricle, but rather than passing entirely into the main pulmonary artery, some of the right ventricular output is diverted into the ascending aorta through a subaortic ventricular septal defect (Figure 6-3). Thus, blood flow through the ascending aorta and aortic arch is increased (as in patients without a ventricular septal defect), and again coarctation of the aorta is not present.

Decreased Pulmonary Blood Flow With Inflow Obstruction

An extremely useful clinical finding in infants with cyanosis is the quality of the right ventricular impulse.

Normally, the right ventricle is easily palpated along the lower sternum or in the subxiphoid area. This is because the right ventricle is the dominant ventricle during fetal life and is anteriorly positioned and the sternum is relatively pliable. The right ventricular impulse is either normal or increased in patients with right ventricular outflow tract obstruction, transposition complexes, or persistent pulmonary hypertension of the newborn. However, if inflow obstruction is present, the right ventricle does not fill normally and thus does not contract to a normal extent. The right ventricular impulse is decreased in such patients. Thus, the presence of a decreased right ventricular impulse in a newborn infant with cyanosis quickly limits the differential diagnosis to the few defects in which right ventricular inflow obstruction is present (Table 6-2), the two most common of which are described next.

Tricuspid Atresia

Anatomic and physiologic considerations. In tricuspid atresia, the tricuspid valve fails to form normally, resulting in an atretic valve with total obstruction of inflow to the right ventricle from the right atrium. Consequently, all of the systemic venous blood crosses the foramen ovale to the left atrium and ventricle. The degree of right ventricular hypoplasia is variable. In the large majority of these infants, a ventricular septal defect is present, promoting the development of a small right ventricle as blood flows from the left ventricle through ventricular septal defect to right ventricle and pulmonary arteries in utero. The great arteries are usually normally related, but d-transposition of the great arteries is present in a small percentage of infants. When the great arteries are transposed, pulmonary blood flow is increased because the pulmonary valve arises directly from the left ventricle, whereas systemic blood flow depends on the size of the ventricular septal defect so that coarctation of the aorta may occur.

FIGURE 6-2. Pulmonary atresia with intact ventricular septum and right ventricular hypoplasia. Fetal flow patterns show systemic and umbilical venous return passing through the foramen ovale, causing it to be a large communication. The ascending aorta receives all of the ventricular output so that the aortic arch and isthmus are large and the ductus arteriosus, in which flow is reversed, is vertically oriented and small. Red lines indicate oxygenated blood, and blue lines indicate desaturated blood. The intermediate purple arrows illustrate mixing of the venous return so that systemic blood has decreased oxygen saturation. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Clinical presentation. Physical examination reveals increasing cyanosis as the ductus arteriosus closes (except in the presence of a large VSD and unobstructed pulmonary blood flow), and the oxygen saturations are similar in all extremities. Tachypnea may be present, but respiratory distress is absent. 'The peripheral pulses and perfusion are normal, and the remainder of the noncardiac examination is usually noncontributory. The right ventricular impulse is decreased, an important finding directing the clinician to consider this diagnosis. Even more specific is a thrill, which may be present when blood flows anteriorly from the left ventricle to the right via a restrictive ventricular septal defect. This is pathognomonic of tricuspid atresia in a cyanotic newborn infant; in all other cyanotic defects with a ventricular septal defect, blood flows from the right ventricle posteriorly to the left so that a thrill is not present. The first heart sound is normal. No extra sounds or clicks are heard. The second heart sound depends on associated defects. It is usually single but will be split if the flow across the ventricular septal defect and pulmonary valve is large. However, at the normal rapid heart rates present at birth, a split second heart sound is difficult to appreciate. If the great arteries are transposed, the aortic component of the second heart sound may be loud. A murmur may be heard as a result of flow through a ventricular septal defect or right ventricular outflow tract obstruction.

FIGURE 6-3. Tetralogy of Fallot. Fetal flow patterns show normal venous return to the right and left ventricles, but some right ventricular output is directed to the ascending aorta, enlarging the aortic arch and causing the ductus arteriosus to shunt left to right. Red lines indicate oxygenated blood, and blue lines indicate desaturated blood. The intermediate purple arrows illustrate mixing of the venous return so that systemic blood has decreased oxygen saturation. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Ancillary tests. Based on clinical findings alone, it is usually possible to limit the differential diagnosis in these infants to cyanosis caused by defects that result in right ventricular inflow obstruction (Table 6-2). Simple ancillary tests usually can then differentiate tricuspid atresia from pulmonary atresia with intact ventricular septum and determine whether there is associated d-transposition of the great arteries:

• The chest radiograph shows a narrow mediastinum when the arteries are transposed and a normal mediastinum when they are normally related.

• The electrocardiogram usually shows right atrial enlargement and decreased right ventricular forces in all of these defects, but the axis is inferior with a normal clockwise loop in pulmonary atresia with intact septum, whereas it is superior (0 to -60 degrees) with a counterclockwise loop in tricuspid atresia and normally related great arteries. Infants with tricuspid atresia and d-transposition of the great arteries may have a similar axis to those with pulmonary atresia (0 to +90 degrees).

• Echocardiography is definitive. No tricuspid valve tissue is seen in the atrioventricular groove, between the right atrium and the right ventricle. Obligatory flow across the foramen ovale (or secundum atrial septal defect) into the left atrium is present and is often directed by a large eustachian valve in the right atrium. The size of the atrial communication, the presence of a ventricular septal defect, the size of the right ventricle and right ventricular outflow tract, the relationship of the great arteries, and the patency of the ductus arteriosus should all be evaluated.

Therapeutic considerations. These infants are considered to have a functional single ventricle because the right ventricle will never function as an adequate pumping chamber in the absence of an adequate inlet. Most infants require a systemic-to-pulmonary artery shunt shortly after birth because of severe cyanosis. Some centers are providing pulmonary blood flow by transcatheter placement of a stent in the ductus arteriosus rather than via a surgical aorto-pulmonary shunt. Subsequently a bidirectional Glenn shunt (superior cavopulmonary connection) and then a modified Fontan operation are performed (see following text). Infants who have a relatively well developed right ventricle and pulmonary valve because of the presence of a ventricular septal defect are only minimally cyanotic and may not need a systemic- to-pulmonary artery shunt. Occasionally, if pulmonary blood flow is very high, a pulmonary arterial band may be needed. Even more uncommon is when the pulmonary obstruction allows for an appropriate amount of pulmonary blood flow under low perfusion pressure so that no surgery in the first months of life is necessary. After the newborn period, these infants progress through staged single-ventricle palliation as described below. Infants with transposed great arteries often develop functional subaortic obstruction (restrictive bulboventricular foramen) and may need a Damus-Kaye-Stansel operation (see following text) to be performed at the time of either the bidirectional Glenn shunt or modified Fontan operation.

Pulmonary Atresia With Intact Ventricular Septum and Hypoplastic Right Ventricle

Anatomic and physiologic considerations. A second category of right ventricular inflow obstructive defects occurs when the tricuspid valve is present but is severely hypoplastic. This is associated with hypoplasia of the right ventricle and atresia of the pulmonary valve. After birth, pulmonary blood flow is entirely dependent on patency of the ductus arteriosus. The systolic pressure in the right ventricle is usually much greater than the systemic systolic pressure because of the right ventricular outflow tract obstruction. As a result of the very high pressure within the right ventricular cavity, embryonic connections of the right ventricular cavity with coronary arteries may persist as coronary sinusoids (Figure 6-4). These connections may perfuse the myocardium with poorly saturated blood and may not communicate with the proximal coronary system, or they may connect to the coronary arteries but with severely stenotic openings. In these situations, part of the coronary arterial circulation is dependent on perfusion from the right ventricle (“right ventricledependent coronary circulation”), which increases the risk of death because of myocardial ischemia.

FIGURE 6-4. Pulmonary atresia with intact ventricular septum and right ventricular hypoplasia. A right ventricular angiogram demonstrating a very hypertrophied diminutive ventricle with extensive filling of both coronary arterial systems by sinusoidal communications with the hypertensive ventricle. Abbreviation: RV, right ventricle.

Clinical presentation. On physical examination, the infant is cyanotic within a few hours after birth and has similar oxygen saturations in all extremities. The peripheral pulses and perfusion are normal. Important noncardiac findings are rarely present. Although the right ventricle is usually generating systolic pressures that greatly exceed systemic pressure, the right ventricular impulse is often decreased because the right ventricle usually receives and ejects only a very small amount of blood. The first heart sound is normal. No extra sounds or clicks are heard. The second heart sound is single and of normal intensity. Murmurs are only occasionally present and reflect either a narrow ductus arteriosus or tricuspid valve regurgitation.

Ancillary tests. The chest radiograph shows a small cardiac silhouette and normal mediastinum, similar to that seen in tricuspid atresia with normally related great arteries.

• The electrocardiogram shows decreased, normal, or increased right ventricular forces, depending on the mass of the right ventricular wall. In contrast to patients with tricuspid atresia, the axis is in the left inferior quadrant (+60 to 90 degrees); this is an important differentiating point.

• The echocardiogram usually shows a small tricuspid valve annulus and a markedly hypertrophied right ventricle with little contraction and often evidence of endocardial fibrosis. The size of the tricuspid valve and right ventricle should be defined. There usually is no apparent right ventricular outflow tract, and there is a unidirectional right-to-left atrial shunt. Color Doppler echocardiography may demonstrate flow in the coronary arterial sinusoids within the myocardial wall. Evaluation of whether the coronary arterial circulation is dependent on the right ventricle is mandatory, and cardiac catheterization may be necessary to resolve this issue.

Therapeutic considerations. Treatment of these patients must be individualized and is often difficult and complicated. The major question is whether the tricuspid valve and right ventricle can grow enough to support some or all of the pulmonary circulation if right ventricular outflow obstruction is relieved or whether the patient must be treated as a functional single ventricle. In many of these patients, the very small tricuspid valve precludes its use in the circulation. However, there is a continuum between these patients and those with pulmonary valve atresia and a normal-size right ventricle (see below); in those patients with a moderately hypoplastic tricuspid valve and right ventricle, creation of continuity between the right ventricle and pulmonary artery may result in remarkable growth of the tricuspid valve and right ventricle. Placement of a systemic-to-pulmonary artery shunt may be necessary in addition to right ventricular outflow tract reconstruction to ensure adequate pulmonary blood flow, at least in the short term. Patients with an extremely hypoplastic right ventricle, right ventricle-dependent coronary circulation, or a right ventricle that fails to grow adequately after relief of right ventricular outflow tract obstruction are treated as functional single ventricles. They require a systemic-to-pulmonary artery shunt (or a stent in the ductus arteriosus) and later are candidates for a bidirectional Glenn shunt and modified Fontan operation (see following text).

Decreased Pulmonary Blood Flow With Outflow Obstruction

Pulmonary Atresia With Intact Ventricular Septum and a Normal-Size Right Ventricle

Anatomic and physiologic considerations. Pulmonary atresia with an intact ventricular septum is not necessarily associated with a hypoplastic right ventricle. When the right ventricular cavity is well formed, the tricuspid valve is usually of nearly normal size but may be severely insufficient. Coronary arterial sinusoids do not develop, likely in part because the right ventricle cannot generate high pressures because of the tricuspid regurgitation. Additionally, by the time the outflow obstruction develops during fetal life, the embryonic sinusoids may have already regressed. Interestingly, the pulmonary arteries are usually normally developed despite the fact that they receive only a small amount of the fetal combined ventricular output through the ductus arteriosus.

Clinical presentation. The infant is cyanotic within a few hours after birth with similar oxygen saturations in all extremities. Mild tachypnea is present, but respiratory distress is absent. The peripheral pulses and perfusion are normal, and the noncardiac examination is unremarkable. Unlike the infant with the hypoplastic right ventricle, however, the large volume of blood passing into the right ventricle is associated with a normal to increased right ventricular impulse. The first heart sound is normal or may be obscured by the tricuspid regurgitation murmur. No extra heart sounds are present. The second heart sound is single. An early, blowing systolic murmur heard best at the left lower sternal border and radiating toward the right anterior chest is caused by the tricuspid valve regurgitation.

Ancillary tests

• The chest radiograph usually shows an enlarged right atrium because of tricuspid insufficiency, and the central blood vessels are of normal size.

• The electrocardiogram is similar to that seen in pulmonary atresia with a hypoplastic tricuspid valve, except that right ventricular hypertrophy is more common and right atrial enlargement may be especially pronounced.

• The echocardiogram shows a nearly normal tricuspid valve annulus. The z score, a measure of the number of standard deviations from the normal mean diameter, is usually greater than -2. Severe tricuspid regurgitation with an enlarged right atrium is present. The right ventricle, which is well formed (inflow, body, and outflow components are all present), contracts normally, and endocardial fibroelastosis is not seen. The pulmonary arteries and pulmonary valve are normal in size, and the pulmonary circulation is exclusively from blood passing through the ductus arteriosus.

Therapeutic considerations. These infants require administration of prostaglandin E1 to maintain adequate pulmonary blood flow through the ductus arteriosus. Pulmonary valvuloplasty performed in the cardiac catheterization laboratory is the procedure of choice. Access to the pulmonary artery from the right ventricle usually is achieved by radio-frequency perforation of the atretic valve, and then a balloon valvuloplasty is performed. Many infants do very well after this procedure. However, sometimes the oxygen saturation is quite low because the hypertrophied and noncompliant right ventricle cannot accept an adequate amount of systemic venous return even after a successful valvuloplasty. In these cases, it is necessary to continue prostaglandin E1 administration after the procedure or to perform a systemic-to-pulmonary artery shunt. The ventricle, though, often rapidly remodels, and the prostaglandin E1 infusion or the shunt may be necessary for only a short period of time.

Critical Pulmonary Valve Stenosis

Anatomic and physiologic considerations. Critical pulmonary valve stenosis is very similar to pulmonary atresia with a normal-size right ventricle and is likely caused by similar events during cardiovascular development. Instead of an imperforate pulmonary valve, forward flow of blood is present. The distinction between critical and severe stenosis is based on a systemic arterial desaturation below some arbitrary level, usually about 90% to 92%, in the absence of a patent ductus arteriosus. Both critical and severe stenosis of the pulmonary valve cause right ventricular systolic pressures to be at or, most often, higher than systemic levels. If the degree of stenosis is critical, the ventricle cannot eject the entire systemic venous return across the pulmonary valve. In these cases, some of the systemic venous return crosses the foramen ovale to the left atrium, causing systemic arterial desaturation.

Clinical presentation. The clinical presentation of infants with critical pulmonary valve stenosis is similar to that of infants with pulmonary atresia. The right ventricular impulse may be increased if there is a large amount of tricuspid regurgitation. The second heart sound is single. Although there is forward flow across the pulmonary valve, it is so minimal that it cannot be heard, and the limited valve opening is not associated with an ejection click. A murmur of tricuspid regurgitation is usually present.

Ancillary tests

• The chest radiograph and electrocardiogram are similar to those seen in pulmonary atresia.

• Echocardiography is also similar to that seen in pulmonary atresia, except there is flow across the pulmonary valve and coronary sinusoids are rarely present. Forward flow may be so limited that it cannot be distinguished from the turbulence in the main pulmonary artery caused by ductal flow striking the atretic valve. Thus, definitive evidence of valve patency is often a small jet of pulmonary regurgitation visualized by color Doppler in the right ventricular outflow tract (Figure 6-5).

Therapeutic considerations. Although infants with severe pulmonary valve stenosis may be stable, those with critical obstruction of the pulmonary valve require administration of prostaglandin E1 to maintain adequate pulmonary blood flow through the ductus arteriosus. Many infants do very well after a pulmonary valvuloplasty performed in the catheterization laboratory. Similar to patients with pulmonary atresia, it may be necessary to establish a second source of pulmonary blood flow, at least temporarily, via a systemic-to-pulmonary artery shunt even after a successful valvuloplasty.

FIGURE 6-5. Critical pulmonary stenosis. Two-dimensional echocardiography demonstrates a well- developed pulmonary valve that does not appear to open (A). Color Doppler demonstrates a narrow jet of pulmonary insufficiency (B, see arrow), indicating that the pulmonary valve is critically obstructed rather than atretic. The flow distal to the pulmonary valve represents not flow crossing the valve but rather ductal flow toward the valve (red) and reversal of that flow toward the branch pulmonary arteries (blue). Abbreviations: PA, pulmonary artery; RV, right ventricle.

Dextroposition Syndromes (Including Tetralogy of Fallot)

Anatomic and physiologic considerations. An entirely separate group of defects with right ventricular outflow obstruction are those associated with anterior malalignment of the outlet ventricular septum relative to the trabecular septum, resulting in right ventricular outflow tract obstruction. Tetralogy of Fallot is the most common of these defects and is characterized by anterior displacement of the infundibular or outlet septum, a large and anteriorly malaligned outlet ventricular septal defect, and narrowing of the right ventricular outflow tract (Figure 6-3). The aortic root is dextroposed, and the amount of aortic valve overriding is variable (15% to 90%). However, the aorta is still related anatomically to the left ventricle, as indicated by the fibrous continuity between the aortic and mitral valves. The type of pulmonary stenosis is also highly variable and may occur at subvalvar, valvar, and/or supravalvar levels. In the extreme situation, pulmonary atresia is present. If so, the pulmonary arteries may arise from a variety of sources.

To understand the possible sources of pulmonary blood flow, one must be aware of the embryology of the pulmonary vascular bed (Chapter 1). The central pulmonary arteries and ductus arteriosus arise from tissues derived from the sixth aortic arch. The peripheral pulmonary arteries are derived from an entirely different embryologic source, the capillary plexus of the embryonic lung. In the normal situation, the central pulmonary arteries invade the parenchyma of the lung along with intersegmental vessels of the descending aorta, such as the bronchial arteries. Normal central pulmonary arteries present in any lung segment are thought to send inhibitory signals that prevent connections with the intersegmental arteries.

When pulmonary valve atresia occurs in the absence of a ventricular septal defect, the aortic arch tissues develop normally, and normal central pulmonary arteries develop because they receive blood flow through the ductus arteriosus. However, the dextroposition syndromes develop in part because of abnormalities in the embryological development of the aortic arches, and thus the central pulmonary arteries are often very hypoplastic and may not connect to every lung segment.

In the absence of a connection between the central pulmonary artery and the distal vascular bed in a given lung segment, the inhibitory signals are absent, and other connections are made. Most commonly, intersegmental vessels from the descending aorta, called direct major aorto-pulmonary collateral vessels, connect to the lung segment (Figure 6-6A). Occasionally, these vessels do not develop, and indirect collateral vessels derived from the head and neck vessels supply that segment (Figure 6-6B). In either situation, small central pulmonary arteries may fill with blood in a retrograde fashion from small connections peripherally, but central connections are not present (Figure 6-6C).

Clinical presentation. The initial presentation of the infant with any of these “dextroposition” defects depends entirely on the amount of pulmonary blood flow. Pulmonary blood flow increases greatly as pulmonary vascular resistance falls after birth in those infants with severe obstruction and a persistently patent ductus arteriosus. These infants may be cyanotic very transiently, if at all, and soon do not appear cyanotic at rest. Typically, during the first hours of life, they are cyanotic only when crying or feeding. Over the first few hours and days, the ductus arteriosus begins to close, and cyanosis becomes more apparent.

On physical examination, a variable degree of cyanosis is present, and although the infant may be tachypneic, respiratory distress is not evident. Because pulmonary arterial resistance is less than systemic arterial resistance, any shunt across the ductus arteriosus must be from the aorta to the pulmonary artery so that upper and lower body arterial oxygen saturations are the same, a finding that can help to differentiate these infants with dextroposition defects from those with d-transposition of the great arteries (Table 6-3). The pulses are normal or increased if there is a large ductus arteriosus or aorto-pulmonary collateral flow. The cardiac examination shows a normal to increased precordial impulse and a single second heart sound. A systolic or continuous murmur reflecting flow through the collateral vessels may be heard over the lung fields and is often prominent in the back.

The remainder of the physical examination is normal except when the cardiac defect occurs in the presence of a specific syndrome. Unlike infants with other forms of cyanotic heart disease, associated noncardiac findings are quite common, particularly when the aortic arch is right sided (Chapter 15). A relatively large proportion of patients are syndromic or have chromosomal anomalies. The group of syndromes with a microdeletion on the short arm of chromosome 22 (deletion 22q11 syndrome) include DiGeorge syndrome, CATCH-22, velocardiofacial syndrome, conotruncal face anomaly, and Shprintzen syndrome, all of which have overlapping clinical findings. These findings, which include hypertelorism, low-set ears, micrognathia, and palatal anomalies, are commonly present in affected infants. These infants should undergo testing to assess for genetic disorders.

Ancillary tests

• The chest radiograph shows a dominant right ventricular contour with absence of the main pulmonary artery contour and shows the classic “boot-shaped” heart (Figure 6-7). Evaluation of the central pulmonary vessels is important. Decreased central vascularity is often present, but this does not necessarily reflect decreased pulmonary blood flow. Pulmonary blood flow is dependent not on the size of the central vessels but rather on the conductance of the peripheral vascular bed. A large volume of blood may be passing through a ductus arteriosus or through aorto-pulmonary collateral vessels to the lungs without enlarging the central arteries.

• The electrocardiogram is normal during the first few days of life, showing the normal right ventricular dominance pattern of upright T waves and dominant R waves in the right precordium. However, unlike the electrocardiogram from a normal infant in which the T waves become inverted during the first week of life, the upright T waves persist because the systolic pressure in the right ventricle remains at systemic levels. The oxygen saturation may be in the low to mid-90s in many infants with small central pulmonary arteries; this indicates pulmonary blood flow that is about three times the normal systemic blood flow. The presence of a right aortic arch is an important finding that is commonly present in dextroposition defects and increases the likelihood of a chromosome 22 microdeletion. The absence of a rightward deflection of the trachea or of a left-sided aortic knob and the presence of a descending aorta to the right of the spine are all suggestive of the presence of a right aortic arch on the chest radiograph.

• The echocardiogram shows the internal cardiac anatomy of an outlet ventricular septal defect and an aorta overriding the ventricular septum to a variable degree. The anatomy of the right ventricular outflow tract and pulmonary valve, the central pulmonary arterial anatomy, associated muscular ventricular septal defects, the coronary arterial anatomy, the side of the aortic arch, and the anatomy of the ductus arteriosus should be determined. In the presence of a patent ductus arteriosus and a patent pulmonary valve, it may not be possible to determine whether blood flow through the ductus arteriosus is necessary for healthy survival until the ductus arteriosus closes. However, the size of the outflow tract and pulmonary valve usually reflect the degree of right ventricular outflow tract obstruction. In pulmonary atresia, it is particularly important to clearly determine the anatomy of the ductus arteriosus. Differentiating the ductus arteriosus from an aorto-pulmonary collateral vessel is sometimes difficult. If the ductus arteriosus is present, it may also connect to only one lung. If the pulmonary valve is atretic, a ductus arteriosus may or may not be present. Thus, newborns with pulmonary atresia and ventricular septal defect usually undergo cardiac catheterization and/or magnetic resonance imaging to precisely determine anatomy.

FIGURE 6-6. Aortic or selective angiograms performed in a patient with pulmonary atresia, ventricular septal defect, and aorto-pulmonary collateral vessels. A. Descending aortic angiogram shows large direct aorto-pulmonary collateral vessels arising from the mid-thoracic aorta. B. An angiogram performed in the right innominate artery demonstrates indirect collateral vessels arising from the right subclavian artery and perfusing the right lung. C. A selective angiogram in a direct aorto-pulmonary collateral vessel demonstrates distal filling of diminutive bilateral true pulmonary arterial circulation.

FIGURE 6-7. A chest radiograph in an infant with tetralogy of Fallot. This demonstrates a narrow mediastinum by absence of the normal pulmonary arterial contour in the upper left heart border and the dominant right ventricular contour making the left border take on a horizontal, or bootshaped, appearance. An umbilical artery catheter is present.

Therapeutic considerations. Infants with reasonably well developed pulmonary arteries undergo complete repair of their defects, usually within the first few months of life. Infants who require intervention but are either too premature or at excessive risk from cardiopulmonary bypass because of secondary organ dysfunction may undergo a palliative procedure first. Palliation may be via a catheter approach, consisting of a balloon pulmonary valvuloplasty, stenting of the ductus arteriosus, or, more rarely, stenting of the right ventricular outflow tract. Alternatively, systemic-to-pulmonary artery shunt may be placed surgically.

Therapy is much more complex in patients with hypoplastic central pulmonary arteries because the sources of pulmonary blood flow are complicated and different in every patient. Those infants in whom the blood supply to one or both lungs arises from the ductus arteriosus require surgery in the newborn period to preclude loss of these lung segments when the ductus closes. In contrast, surgery may be delayed for weeks or months in those infants whose pulmonary blood flow is supplied by aortopulmonary collateral vessels. The goal of therapy for these infants is reconstruction of the pulmonary arteries such that closure of the ventricular septal defect is possible, but this often involves a series of procedures in the catheterization laboratory and operating room.

Heterotaxy Syndromes (Right and Left Atrial Isomerism)

Anatomic and physiologic considerations. Hetero- taxy syndromes represent constellations of cardiac and noncardiac findings in which the situs of the neonate is uncertain (Chapter 1), and thus they are also called situs ambiguous. They may be divided into apparent bilateral right sidedness, also known as asplenia syndrome, and bilateral left sidedness, or polysplenia syndrome. This is based on the fact that the spleen is a left-sided structure; unfortunately, the presence or absence of functioning splenic tissue does not always correlate with the finding of right or left sidedness. Of all the findings that occur in one or the other syndrome, the most reproducible is the anatomy of the atrial appendages. The right and left appendages are very different. The right atrial appendage is blunt, has a wide opening to the atrium, and has pectinate muscles that extend to the anterior wall of the atrium. In contrast, the left atrium is long and fingerlike, and has a narrow opening to the atrium and limited pectinate muscles that do not extend anteriorly. Because of these reproducible differences in the atrial appendages, the heterotaxy syndromes have been termed “right atrial isomerism” or “left atrial isomerism” (although the term refers to the appendages rather than to the body of the atrium).

In right atrial isomerism, obstruction of the pulmonary outflow is almost universal, and atresia of the pulmonary valve is frequently present. The heart may be in either side of the thorax. Associated cardiac and noncardiac findings are numerous. Additional cardiovascular findings include bilateral superior vena cavae, bilateral sinus nodes, absence of the coronary sinus, a complete atrioventricular septal defect or atresia of one of the atrioventricular valves (rarely are two separate atrioventricular valves present), dextroposition of the aorta, and an almost pathognomonic finding of juxtaposition of the inferior vena cava and descending aorta. The pulmonary arterial anatomy usually mirrors that of the bronchi, exhibiting bilateral right-sided morphology. The pulmonary veins usually connect anomalously, often to one or both superior vena cavae. If they connect directly to the atria, they do so symmetrically into both atria. The hepatic veins also frequently connect abnormally, directly to the atria and separate from the inferior vena cava. Noncardiac findings include a midline liver, bilateral right bronchial and lung morphology, absence of a functioning spleen, and malrotation of the intestine.

Clinical presentation. The clinical presentation of the newborn with right atrial isomerism is similar to that of any infant with ductal-dependent pulmonary blood flow. Initially, the saturations are high enough that cyanosis may be appreciated only when the infant is crying or feeding, but eventually cyanosis increases as the ductus arteriosus closes. Rarely, pulmonary venous obstruction is severe enough to cause significant pulmonary edema, which is associated with both severe respiratory distress and cyanosis. Specific clinical findings include a midline or leftward liver, which can be appreciated by percussion, and a cardiac impulse and heart sounds more prominent in the right chest. The second heart sound is single, and murmurs are often absent but, if present, are usually heard best over the lung fields.

Ancillary tests

• The chest radiograph often shows a right-sided heart and/or stomach, a midline or leftward liver, decreased central pulmonary vascularity, and occasionally bilateral minor fissures, indicative of two lungs of rightsided morphology. The mediastinum is often difficult to interpret because the aorta usually arises abnormally and bilateral vena cavae are present.

• The electrocardiogram is highly variable because of the variability in the position of the heart and the intracardiac findings. There are usually prominent anterior forces since the ventricular chamber ejects into the anterior aorta, but those forces may be in the right or the left chest, and there is usually no evidence of a septal Q wave in the precordial leads on either side of the chest.

• The echocardiogram accurately defines the anatomic details in right atrial isomerism if performed in a careful and thorough manner.

Therapeutic considerations. These patients all have a functional single ventricle. Almost all will need a systemic-to-pulmonary artery shunt in the newborn period. Subsequently, a bidirectional Glenn shunt (usually bilateral bidirectional because there are two superior vena cavae) and modified Fontan operation may be performed (see following text). The connection of the hepatic veins is critically important to determine before the modified Fontan procedure, as they must be included in the conduit rather than remaining connected to the atrium.

Left atrial isomerism presents with a wide constellation of findings as well but usually is not associated with significant obstruction to pulmonary blood flow. Occasionally, however, there may be significant obstruction with associated cyanosis so that this syndrome should be considered in the infant presenting with cyanosis and uncertain situs. The constellation of findings seen in left atrial isomerism is discussed in Chapter 7.

l-Malposition of the Aorta With Pulmonary Stenosis/ Atresia

Anatomic and physiologic considerations. l-malposition of the aorta is often associated with a ventricular septal defect and subvalvar and valvar pulmonic stenosis. In this condition, abnormal l-looping of the heart and rotation of the outflow tracts are present. As described earlier, there is both atrial-ventricular and ventricular-arterial discordance (Figure 6-1B). The tricuspid valve (which is the left, or pulmonary venous, atrioventricular valve) connects to the systemic right ventricle and often has an Ebstein malformation (inferior displacement of the septal leaflet; see following text). However, tricuspid regurgitation is rarely severe in this defect. Occasionally, there is dextrorotation of the heart and, more rarely, true situs inversus, which often lead to the erroneous diagnosis of heterotaxy syndrome. In the presence of pulmonary outflow tract obstruction, a ventricular septal defect is almost always present so that some of the desaturated blood that enters the left ventricle from the right atrium passes through the ventricular septal defect into the ascending aorta. Sometimes both atrioventricular valves empty into the left ventricle, a condition known as double-inlet left ventricle. If this occurs, the right ventricle is usually only a rudimentary outflow chamber, and the physiology is that of a functional single ventricle. Mixed pulmonary and systemic venous blood passes through the ventricular septal defect and small right ventricle and then into the aorta. The size of the ventricular septal defect must be evaluated to ensure that it is large enough so that all of the systemic output can pass through it without obstruction. Alternatively, instead of double-inlet left ventricle, the tricuspid valve may override the ventricular septum (tricuspid valve straddling).

Clinical presentation. The physical findings are dependent on the specific defect present. The precordial impulse is usually normal or mildly increased in the absence of situs inversus since the left ventricle is located adjacent to the normal right ventricle. The quality of second heart sound often provides a clue to the diagnosis. Because the aorta lies anteriorly and leftward (or rightward in situs inversus), the second heart sound is single, very loud, and heard more laterally than usual. A harsh mid-frequency systolic murmur is heard in the mid-parasternal area and reflects flow through the ventricular septal defect. This murmur is difficult to separate from the pulmonary outflow murmur, which may be of somewhat higher frequency and which radiates into both lung fields.

Ancillary tests

• The chest radiograph shows mesocardia and an unusual left heart contour as a result of the l-transposed aorta, especially in older infants. The left-sided aorta is seen at the left upper mediastinal border (Figure 6-8).

• The electrocardiogram is variable, depending on the location of the heart in the chest, but it frequently shows Q waves in the anterior precordial leads and evidence of biventricular hypertrophy, with prominent R and S waves. Atrioventricular block occurs occasionally, but it is much more frequent in left atrial isomerism. If Ebstein anomaly of the tricuspid valve is present, pre-excitation may be seen, and supraventricular tachycardia may occur.

• The echocardiogram shows the findings discussed in the preceding discussion. It is important to clearly determine the atrial-ventricular connections to exclude double-inlet left ventricle or straddling of the tricuspid valve, both of which affect the ultimate surgical approach to the patient. The morphology and function of the tricuspid valve, the ventricular septum, the subpulmonary region, and the pulmonary valve should also be determined.

Therapeutic considerations. The approach to therapy in an individual patient depends on the associated anomalies. Infants without associated intracardiac abnormalities do not require specific therapy. However, even in the absence of other anomalies, long-term follow-up studies indicate a high incidence of acquired systemic ventricular dysfunction, heart failure, systemic atrioventricular valve (tricuspid) regurgitation, arrhythmias, and sudden death. A ventricular septal defect is the most commonly associated defect and will often require surgical closure. Because of the abnormal course of the conduction system, complete atrioventricular block is common after closure of a ventricular septal defect, and many patients will need permanent pacemaker placement. In addition, there is an incidence of acquired atrioventricular block in later life, even in the absence of surgical intervention.

FIGURE 6-8. A chest radiograph in an infant with l-transposition of the great arteries. This shows a prominent shadow in the left upper mediastinum that is caused by the leftwardascending aorta. This gives the left heart border a straight appearance that is characteristic of this defect.

Decreased Pulmonary Blood Flow With Valvar Regurgitation

Valvar regurgitation is a rare cause of decreased pulmonary blood flow, but regurgitation of the tricuspid valve is much more common than that of the pulmonary valve. Regurgitation of the tricuspid valve causes backflow of blood into the right atrium, increasing right atrial pressures. This causes a right-to-left atrial shunt across the foramen ovale and cyanosis. Pulmonary valve regurgitation is extremely rare and occurs almost exclusively as part of a syndrome called tetralogy of Fallot with absent pulmonary valve (see following text). Pulmonary valve regurgitation does not increase right atrial pressures.

The course of cyanosis in the neonate with valvar regurgitation is often quite different from that of an infant with obstruction of pulmonary blood flow. Although both may have progressive cyanosis in the first few hours to days of life as the ductus arteriosus closes, the neonate with outflow obstruction requires intervention, whereas the neonate with valvar regurgitation may show a spontaneous increase in arterial oxygen saturation after a few days of very low saturations. This is because pulmonary vascular resistance affects the amount of valvar regurgitation but not the amount of proximal obstruction. Over the first weeks of life, pulmonary vascular resistance decreases, beginning at the same time but over a longer time course than the closure of the ductus arteriosus. The neonate with valvar regurgitation may be dependent on blood flow through the ductus arteriosus while the pulmonary vascular resistance is high. However, as pulmonary vascular resistance decreases during the first weeks of life, the degree of valvar regurgitation decreases and allows more blood to enter the pulmonary vasculature.

Ebstein Anomaly

Anatomic and physiologic considerations. Ebstein anomaly is characterized by varying degrees of inferior displacement of the septal and posterior (mural) leaflets of the tricuspid valve (Figure 6-9A). This is the most common cause of cyanosis resulting from valvar regurgitation. Displacement of the leaflets into the right ventricle prevents proper coaptation of the leaflets and thus produces severe tricuspid regurgitation. Because the leaflet is displaced below the atrioventricular groove, the regurgitation is not only into the right atrium but also into a component of the right ventricle. This is called the atrialized right ventricle, which may dilate greatly along with the right atrium.

In the fetus, the severe regurgitation and displacement of the septal leaflet of the tricuspid valve in Ebstein anomaly drastically reduces blood flow across the right ventricular outflow tract and increases flow across the foramen ovale. Thus, there may be a secondary abnormality in the development of the right ventricular outflow, the most severe abnormality being pulmonary valve atresia. Also, the large increase in flow across the foramen ovale is usually associated with a large secundum atrial septal defect. The increased right atrial pressures in the fetus also may be associated with hydrops fetalis, which may lead to fetal demise.

Clinical presentation. The neonate with Ebstein anomaly, even of only moderate severity, usually presents with profound cyanosis when the ductus arteriosus begins to close. Peripheral pulses and perfusion are usually normal. The liver is usually normal, although it occasionally is large and pulsatile. The precordium is hyperactive because a large volume of blood is passing back and forth between the right atrium and ventricle. Heart sounds are often complex and difficult to interpret because multiple systolic clicks may be present. It is worthwhile remembering that a cyanotic infant with too many heart sounds is likely to have Ebstein anomaly. A loud, harsh systolic murmur at the lower left sternal border reflecting tricuspid regurgitation is heard and radiates to the right.

Ancillary tests

• The chest radiograph is often dramatically abnormal. The heart appears globular and markedly dilated, filling much of the chest, and the pulmonary vascular markings are decreased. Ebstein anomaly is one of the very few conditions that presents with marked cardiomegaly at birth.

• The electrocardiogram usually shows marked right atrial enlargement (peaked P wave in leads II, III, and V1) and variable right ventricular forces. A short PR interval and a delta wave of pre-excitation are sometimes present, and supraventricular tachycardia may occur in these infants.

• The echocardiogram is diagnostic, except in the rare infant in whom inferior displacement of the tricuspid valve is uncertain and other causes of tricuspid regurgitation must be considered. Usually, a large degree of separation between the hinge point of the leaflet and the atrioventricular groove is present, and the mural leaflet is small and dysplastic. Another pathognomonic finding is the location and direction of the orifice of the valve, which is indicated by the regurgitation jet. Whereas color Doppler demonstrates regurgitation beginning near the atrioventricular groove in other causes of tricuspid regurgitation and goes superiorly, in Ebstein anomaly the jet begins well down toward the apex of the ventricle and may go inferiorly. It is important to carefully evaluate the size of the true right ventricle, outflow tract, and pulmonary valve because this often determines whether the cyanosis will regress spontaneously or whether neonatal surgery will be necessary. The absence of forward flow of blood across the pulmonary valve is not diagnostic of pulmonary valve atresia. Pulmonary arterial pressures may be maintained at systemic levels by flow through a patent ductus arteriosus. If the pulmonary arterial pressure exceeds the pressure that the right ventricle can generate because of the presence of tricuspid regurgitation, the pulmonary valve will not open. In the absence of forward flow, color Doppler evidence of pulmonary regurgitation verifies the patency of the valve. This is very important because neonatal surgery still carries significant mortality and may be unnecessary. The pulmonary arteries are well developed even if the pulmonary valve is atretic, and the left-sided structures are normal.

FIGURE 6-9. Ebstein anomaly. A. Ebstein anomaly showing marked displacement of the septal and posterior leaflets of the tricuspid valve, well below the atrioventricular groove, leading to impaired coaptation of the three leaflets and tricuspid insufficiency. Also noted is the large atrialized right ventricle caused by this displacement, consisting of right ventricular muscle proximal to the orifice of the tricuspid valve (aRV). B. The cone reconstruction of the tricuspid valve consists of detachment of the posterior and septal leaflets of the tricuspid valve, plication of the atrialized right ventricle, and then refashioning and reattachment of the leaflets more superiorly, near the atrioventricular groove, creating the shape of a cone.

Therapeutic considerations. The fact that tricuspid regurgitation often improves as the pulmonary vascular resistance decreases over the first few weeks of life should be considered when planning therapy for these patients. As discussed earlier, cyanosis may gradually decrease, so continuing an infusion of prostaglandin E1 for several weeks may be advisable rather than performing a potentially unnecessary systemic-to-pulmonary artery shunt or complex tricuspid valve surgery. Conversely, if the pulmonary valve is well formed and the regurgitation is severe, some clinicians recommend early ligation of the ductus arteriosus to promote forward flow across the valve. Newer corrective surgical techniques are being developed, and the cone reconstruction has shown very good early results, as shown and described in Figure 6-9B. The atrial septal defect is large and is often sufficient to maintain adequate systemic output, and thus an atrial septostomy is not necessary at birth. Later in life, it is often necessary to close the atrial septal defect, even in patients with mild Ebstein anomaly.

Other Causes of Tricuspid Regurgitation

Other causes of tricuspid regurgitation are much less common than Ebstein anomaly. The tricuspid valve may be dysplastic but without displacement of the septal leaflet, causing severe regurgitation. The clinical presentation, results of ancillary tests, and therapy depend on the amount of regurgitation and are similar to that described above for Ebstein anomaly. Ischemic damage to the papillary muscles of the tricuspid valve related to perinatal asphyxia is discussed in Chapter 9.

Absent Pulmonary Valve Syndrome

Anatomic and physiologic considerations. Pulmonary regurgitation is extremely rare and usually occurs as tetralogy of Fallot with absent pulmonary valve syndrome. Rarely, the ventricular septum is intact in absent pulmonary valve syndrome. The pulmonary valve annulus is mildly hypoplastic but has only vestigial valve remnants. The central branch pulmonary arteries are usually massively dilated, sometimes asymmetrically. A ductus arteriosus rarely exists, and its absence has been implicated in the dramatic pulmonary arterial enlargement. This enlargement may also be caused by a primary defect in the wall of the pulmonary arteries, and histology shows disruption of the elastic layer. Although the unrestricted pulmonary regurgitation in association with the infundibular narrowing and the ventricular septal defect causes right-to-left ventricular shunting and cyanosis, compression of the central bronchi by the dilated pulmonary arteries often contributes to the severe cyanosis.

Clinical presentation. On physical examination, the infant is cyanotic, but in contrast to infants with other causes of cyanotic heart disease, the infant may have severe respiratory distress because of bronchial compression. The distress is both inspiratory and expiratory and may improve dramatically when the infant is placed in a prone position, an important finding that should be considered in evaluating and treating the infant. However, many infants are in sufficient distress that they require endotracheal intubation and mechanical ventilation. The pulses are normal, and the noncardiac examination is usually noncontributory. The precordial impulse is usually markedly increased. The heart sounds often are difficult to appreciate because of the loud murmur. It is best described as a to-and-fro murmur, loudest at the

left upper sternal border but radiating to the entire chest. Few murmurs will be confused with this dramatic sound, except perhaps that of truncal valve stenosis and regurgitation in a neonate with persistent truncus arteriosus (although infants with truncus arteriosus rarely have the same degree of respiratory distress).

Ancillary tests

• The chest radiograph is often dramatically abnormal, showing a massively dilated right or left pulmonary artery or both. The cardiac silhouette is often large. The pulmonary vascular markings may appear increased despite reduced pulmonary blood flow because of the marked pulsatility caused by the pulmonary valve regurgitation.

• The electrocardiogram is similar to that of the neonate with tetralogy of Fallot. It is usually normal but may show right ventricular hypertrophy, particularly after several days when the right precordial T waves have not inverted normally.

• The echocardiogram shows a mild form of tetralogy of Fallot but with massively dilated proximal pulmonary arteries, except when the ventricular septum is intact. Little obvious valve tissue is present in the pulmonary annulus, and severe pulmonary regurgitation is present.

Therapeutic considerations. The pulmonary complications of this syndrome are the principal determinants of successful therapy. The ventricular septal defect is closed, and a conduit is used to reconstruct the right ventricular outflow tract. Despite reparative surgery, tracheobronchial obstruction secondary to the markedly dilated pulmonary arteries often results in chronic respiratory insufficiency.

■ d-TRANSPOSITION COMPLEXES

The other main hemodynamic category of defects that cause cyanosis is the d-transposition complexes. The aorta is “transposed” to the opposite side of the ventricular septum and thus arises from the morphologic right ventricle in patients with d-transposition. In the most common form, simple d-transposition of the great arteries (Figure 6-1A), the heart is normally or d-looped. The right atrium is connected normally to the right ventricle (atrial-ventricular concordance), which, in turn, is connected to the aorta (ventricular-arterial discordance). The left atrium is connected normally to the left ventricle, and the pulmonary artery is also transposed over the ventricular septum and thus arises from the left ventricle. Desaturated systemic venous blood returns to the right atrium and flows across the tricuspid valve into the right ventricle and out the aorta, resulting in profound cyanosis. The pulmonary artery may arise from the left ventricle or may arise with the aorta from the right ventricle. When this arises with a subpulmonary ventricular septal defect and side-byside great vessels, it is called double-outlet right ventricle of the Taussig-Bing type. Other cardiovascular abnormalities are frequently present in patients with the d-transposition complexes and include an atrial septal defect, a ventricular septal defect, subvalvar pulmonary stenosis, subvalvar aortic stenosis (in the presence of Taussig-Bing anomaly), and coarctation of the aorta (almost always in the presence of a ventricular septal defect).

Fetal Physiology

Blood flow patterns are abnormal in the fetus with d-transposition of the aorta, but these patterns are not altered as in the fetus with obstruction of blood flow within the right heart. Because the left and right ventricles eject blood under similar pressures both in the normal fetus and in those with transposition, their relative ability to receive blood (passive compliance) is similar. Thus, venous return enters the ventricles and crosses the foramen ovale in a normal pattern.

The right ventricle ejects blood containing somewhat less oxygen and glucose to the upper body. The brain and heart accommodate the decreased oxygen and glucose delivery by use of local vasodilatory mechanisms that increase blood flow, although there is recent evidence suggesting that metabolic adaptations are incomplete and that neurodevelopmental problems may begin in utero (Chapter 14). The left ventricle, which receives a larger portion of the placental return, ejects blood with relatively high oxygen saturation and glucose concentration to the lower body and placenta. This may cause the pancreas to produce more insulin. Hyperinsulinemia may explain the apparent association of d-transposition of the great arteries with macrosomia and hypoglycemia in neonates.

Blood flow around the aortic arch is normal or somewhat increased in the fetus with simple d-transposition. Thus, these infants rarely have coarctation of the aorta. More commonly, coarctation occurs when there is a sub- pulmonic ventricular septal defect, which directs some of the right ventricular output to the pulmonary artery and through the ductus arteriosus to the lower body, thus decreasing blood flow around the aortic arch. A subpulmonary ventricular septal defect may occur if the pulmonary artery is committed to the left ventricle (d-transposition with ventricular septal defect), but it is much more frequent when the pulmonary artery is committed to the right ventricle (double-outlet right ventricle of the Taussig-Bing type). In this defect, the great vessels are usually side by side, which impinges on the aortic outflow tract, causing subaortic stenosis in addition to the aortic coarctation.

Simple d-Transposition of the Great Arteries

Anatomic and physiologic considerations. Pulmonary blood flow increases significantly after birth, raising left atrial pressure and causes the flap of the foramen ovale to close. The likelihood that this flap is insufficient, as occurs in a secundum atrial septal defect, is no higher in infants with d-transposition than in a normal newborn infant. If the flap of the foramen closes, pulmonary venous return does not enter the right atrium and right ventricle, and the pulmonary and systemic circulations are thus completely separated. In the presence of d-transposition of the great arteries, this prevents the ascending aorta from receiving highly saturated pulmonary venous return and results in severe cyanosis, requiring urgent intervention.

The frequent presence of higher oxygen saturations in the lower extremities in d-transposition of the great arteries is explained by the abnormal blood flow patterns (Table 6-3). Although this is more common and severe when coarctation of the aorta is present, higher oxygen saturations in the lower extremities occur commonly in simple d-transposition without coarctation (especially before a balloon atrial septostomy is performed). This is because the normal postnatal left-to-right ductal shunt raises left atrial pressure if the foramen ovale is restrictive. The continued left-to-right shunting and increased left atrial pressure cause reflex pulmonary arterial vasoconstriction. This increases pulmonary vascular resistance to a level that right-to-left shunting occurs through the ductus arteriosus so that highly saturated blood from the pulmonary artery flows to the descending aorta.

Clinical presentation. Simple d-transposition of the great arteries is the most common form of cyanotic cardiovascular disease and one of the most common forms of symptomatic cardiovascular disease in the newborn.

Unlike the infant with decreased pulmonary blood flow who generally does not have severe cyanosis at birth, the infant with d-transposition of the great arteries is often profoundly cyanotic within minutes after birth. Thus, the newborn infant who presents early with profound cyanosis but without respiratory distress most frequently has d-transposition of the great arteries.

On physical examination the infant is cyanotic in all extremities, although, as discussed above, pulse oximetry may show a higher oxygen saturation in the lower extremities. The infant is tachypneic but not in respiratory distress. The pulses and perfusion are normal. The noncardiac examination is noncontributory. The precordium is active but not increased compared to that of a normal newborn infant. The first heart sound is normal, and the second sound is single and loud but not displaced. Murmurs are rarely present.

Ancillary tests

• The chest radiograph classically shows an “egg on a string” (Figure 6-10) in which the heart is of normal size but the mediastinum is narrow because of posterior and rightward malposition of the pulmonary artery. However, the thymus is frequently present, and narrowing of the mediastinum may not be apparent.

• The electrocardiogram is normal at birth, although evidence of right ventricular hypertrophy is present by several days of age. Over the next few days, if the infant is untreated, the heart enlarges, and pulmonary vascularity increases.

• d-transposition is rapidly diagnosed by two-dimensional echocardiography. On diagnosis, it is important to quickly determine the patency of the ductus arteriosus and of the foramen ovale. Doppler echocardiography should be used to estimate the flow and the pressure difference across the foramen ovale. If a significant pressure difference between the right and left atria is found, the foramen ovale is said to be “restrictive.” Associated abnormalities, such as a ventricular septal defect, coarctation of the aorta, or subvalvar pulmonic stenosis, should be assessed. It is also important to determine the anatomy of the pulmonary and aortic valves and the alignment of their commissures and of the coronary arteries.

FIGURE 6-10. A chest radiograph in an infant with d-transposition of the great arteries. This shows a narrow mediastinum caused by posterior and medial displacement of the pulmonary artery. The left ventricular contour is dominant making the apex of the heart point downward, like an “egg on a string.” A nasogastric tube is present.

Therapeutic considerations. To maintain patency of the ductus arteriosus, prostaglandin E1 (Chapter 12) should be administered to all newborn infants with d-transposition of the great arteries. Although shunting through the ductus arteriosus is typically bidirectional (right to left in early systole and left to right throughout diastole), only left-to-right shunting through the foramen ovale allows highly saturated blood to reach the ascending aorta. If the patient is profoundly cyanotic and the foramen ovale is small and restrictive, an emergency balloon atrial septostomy should be performed. This can usually be done by trained personnel under echocardiographic guidance at the infant’s bedside. After the septostomy, the increased pulmonary blood flow caused by the ductal shunt raises left atrial pressure, which may dramatically increase the left-to-right shunt across the foramen ovale, which in turn increases aortic oxygen saturation.

Definitive surgical repair of simple d-transposition of the great arteries is accomplished by performing the arterial switch procedure, usually in the first week or two of life. The aorta and pulmonary artery are transected just above their respective valves and then sewn to the appropriate ventricle. To maintain coronary perfusion with normal pressure and oxygen saturation, the coronary arteries must be transferred from the aorta to the pulmonary artery (which becomes the neo-aorta). The anatomy of the coronary arteries is frequently abnormal in these patients, but in almost all instances, the coronary arteries can be successfully transplanted into the neo-aorta at the time of surgery.

d-Transposition of the Great Arteries With Ventricular Septal Defect

Anatomic and physiologic considerations. The cardiac defect most commonly associated with d-transposition of the great arteries is a ventricular septal defect. The defect usually lies in the perimembranous region but may be in the muscular septum. When the ventricular septal defect is subpulmonic, it may be associated with redirection of some of the right ventricular output to the pulmonary artery so that coarctation of the aorta is more likely to occur.

Clinical presentation. The clinical presentation of the infant with d-transposition of the great arteries and a ventricular septal defect may be the same or quite different than that of the infant with an intact ventricular septum. Blood tends to flow through the ventricular septal defect to the pulmonary arteries (left-to-right shunting) because the resistance in the pulmonary vascular bed is lower than that in the systemic bed. If the atrial septum is intact, the infant is profoundly cyanotic, and an emergency balloon atrial septostomy is indicated despite the presence of a ventricular septal defect. The only distinguishing features from simple d-transposition may be a short systolic murmur and, occasionally, respiratory distress from the increased left atrial pressures and subsequent pulmonary edema. If, however, a relatively nonrestrictive foramen ovale is present, the left-to-right ventricular shunt increases left atrial filling and causes a large left-to-right atrial shunt that does not decrease with closure of the ductus arteriosus. Thus, these infants may have quite high arterial oxygen saturations, and, indeed, occasionally they are not diagnosed until several weeks of age when they present with evidence of excessive pulmonary blood flow. Implementation of pulse oximetry screening in the newborn should greatly decrease such delayed diagnoses.

Ancillary tests

• The chest radiograph shows an enlarged heart and increased vascularity at an earlier time.

• The electrocardiogram is similar to that seen in simple d-transposition of the great arteries.

• The echocardiogram shows the location and shunting of the ventricular septal defect. The flow and pressure difference across the patent foramen ovale must be assessed. Possible associated defects, such as pulmonary stenosis and coarctation of the aorta, should be determined.

Therapeutic considerations. Definitive surgical repair is accomplished by the arterial switch procedure and closure of the ventricular septal defect. If a subaortic ventricular septal defect is present, the presence of fixed subvalvar and valvar pulmonary stenosis prevents this approach. Instead, a Rastelli or REV procedure is performed, but this is usually delayed for several months or years. In these operations, the ventricular septal defect is closed in such a fashion that the left ventricle ejects into the aorta (an interventricular baffle). Connection of the right ventricle to the pulmonary artery often requires an external conduit (Rastelli procedure), but occasionally the right ventricular outflow tract also can be internally baffled to connect to the pulmonary valve without significant obstruction (REV procedure).

Taussig-Bing Anomaly

Anatomic and physiologic considerations. Doubleoutlet right ventricle of the d-transposition type is commonly referred to as Taussig-Bing anomaly. There is disagreement about what constitutes double-outlet right ventricle as compared to d-transposition with ventricular septal defect. Perhaps the best way to differentiate the two defects is that a subpulmonic conus or infundibulum is present in double-outlet right ventricle but not in d-trans- position with a ventricular septal defect (Figure 6-11). The conus is a structure that is part of the embryologic outflow tract, which is incorporated into the future right ventricle. Thus, the presence of a conus below the pulmonary valve suggests that it is committed to the right ventricle rather than to the left ventricle. This is more than a semantic consideration. The presence of asubpulmonic conus indicates that the pulmonary valve is located more anteriorly and leftward than occurs in simple d-transposition. This position is more likely to encroach on the subaortic outflow tract, and the right ventricle is likely to eject more of its output across the pulmonary valve. Thus, subaortic stenosis and coarctation of the aorta are far more likely to occur in Taussig-Bing anomaly, and complete interruption of the aorta is common (Figure 6-11).

Clinical presentation. On physical examination, the infant is cyanotic but usually not as severely as the newborn with simple d-transposition. There commonly is a significant discrepancy between upper and lower body oxygen saturations, and the lower body pulses may be decreased if coarctation of the aorta is present. If so, respiratory distress and decreased systemic perfusion may be present. The precordium is active, the second heart sound is single, and a short systolic murmur is present.

Ancillary tests

• The chest radiograph and electrocardiogram are not different than those seen in d-transposition of the great arteries with ventricular septal defect.

• The echocardiogram demonstrates the abnormal relationships of the great arteries and shows both the sub- pulmonic conus and a separate subaortic conus. The subpulmonic ventricular septal defect is readily demonstrated. The anatomy of the subaortic region, the aortic arch, and the coronary arteries should be characterized. The relative sizes of the great arteries should also be evaluated because major size discrepancies may complicate the arterial switch operation.

Therapeutic considerations. Definitive surgical repair is accomplished in early infancy by the arterial switch procedure and closure of the ventricular septal defect, although marked discrepancy in semilunar valve size, coronary artery abnormalities, and the obstruction of the left ventricular outflow tract after closure of the ventricular septal defect all adversely affect the long-term outcome. Associated defects, such as coarctation of the aorta, are repaired at the same time.

■ PALLIATIVE PROCEDURES

Systemic-to-Pulmonary Artery Shunts

A shunt may be placed between the aorta or branch of the aorta and pulmonary artery in two groups of infants who do not have enough pulmonary blood flow because of severe pulmonary stenosis or pulmonary atresia: those who are too small to undergo open-heart repair of all defects and those in whom open-heart repair is not feasible. The shunt must be large enough to provide adequate pulmonary blood flow as the patient grows but not so large that the patient develops ventricular dysfunction because of volume overload. In addition, placement of the shunt should avoid distortion of the pulmonary artery.

The Blalock-Taussig shunt was one of the first surgeries performed in children with congenital cardiovascular disease. As originally described, the subclavian artery was divided, and the proximal end was anastomosed to the main branch pulmonary artery on the same side (Figure 6-12). More commonly, a modified Blalock-Taussig shunt is performed by placing a Gore-Tex tube graft between the subclavian or innominate artery and the branch pulmonary artery on the same side. The size of the shunt is determined by the size of the Gore-Tex tube graft. A central shunt is performed by placing a Gore-Tex tube graft between the ascending aorta and main pulmonary artery (Figure 6-12). This shunt has a very low likelihood of causing distortion of the pulmonary artery. In patients with very hypoplastic or otherwise distorted pulmonary arteries, atypical shunts are most often constructed with a piece of Gore-Tex tubing connecting the aorta or subclavian artery to a branch pulmonary artery. Alternatively, some avoid surgery and use transcatheter placement of a stent in the ductus arteriosus to maintain pulmonary blood flow.

FIGURE 6-11. Echocardiographic images of Taussig-Bing anomaly. There is with subaortic narrowing relative to the large subpulmonic region (A) with acceleration noted by color Doppler (B, see arrow). There is marked transverse arch hypoplasia (C) with acceleration at its lower end due to a coarctation (D, see arrow). Abbreviations: Ao, ascending aorta; PA, pulmonary artery; RV, right ventricle.

FIGURE 6-12. Diagram of most commonly performed sys- temic-to-pulmonary artery shunts. Abbreviations: LPA, left pulmonary artery; MPA, main pulmonary artery; RPA, right pulmonary artery.

After surgical or catheter-based placement of a systemic-to-pulmonary artery shunt, the magnitude of pulmonary blood flow is determined primarily by shunt diameter and length, and secondarily by the relation of the systemic-to-pulmonary vascular resistances. The goal is usually to keep the oxygen saturations 75% to 85%, which usually provides adequate systemic oxygen delivery and does not create excessive volume overload for the ventricle(s) (see following discussion).

Patients who have had a shunt procedure are at risk of infectious endocarditis, paradoxical embolism, brain abscess, and shunt thrombosis. Low-dose aspirin is usually administered daily to decrease the risk of shunt thrombosis, and clopidogrel has been added in some high-risk patients, although studies as to its efficacy and safety are ongoing. Shunt thrombosis should always be considered if a patient becomes acutely hypoxemic and the shunt murmur becomes very soft or absent.

Approach to the Patient With a Functional Single Ventricle

Anatomy

Unfortunately, many complex cardiac defects result in a functional single ventricle. The possible anatomic variations are numerous; the most common defects are discussed in Chapters 6 to 8, and complete lists may be found in standard textbooks.

Physiology

Mixing of the systemic and pulmonary circulations occurs in infants with a functional single ventricle. The output from the single ventricle is divided between the two circulations; the proportion going to the systemic and pulmonary vascular beds is determined by the relative resistance to flow within the respective circulation. Resistance to pulmonary blood flow is determined by the amount of subvalvar and valvar pulmonary obstruction, the size of the ductus arteriosus (or surgically placed shunt) if present, and the pulmonary vascular resistance. The resistance to systemic blood flow is determined by the degree of subvalvar and valvar aortic obstruction, aortic arch hypoplasia or coarctation, the size of the ductus arteriosus, and the systemic vascular resistance.

Initial Treatment

Patients with a functional single ventricle usually have too much or too little pulmonary blood flow. Those without enough pulmonary blood flow usually have pulmonary atresia or severe pulmonary stenosis. At birth, they are cyanotic and are dependent on flow of blood through the ductus arteriosus to maintain pulmonary blood flow. Once the ductus arteriosus begins to close, cyanosis increases. These infants require prostaglandin E1 administration (Chapters 5 and 12) and then placement of a systemic- to-pulmonary artery shunt (see earlier discussion).

Some patients have a mild amount of pulmonary stenosis shortly after birth that limits pulmonary blood flow and prevents severe congestive heart failure. The degree of pulmonary stenosis tends to increase with time so that these patients become progressively more cyanotic. A systemic-to-pulmonary artery shunt may be necessary at 2 to 3 months of age, but some patients may be able to wait until they are candidates for a bidirectional Glenn shunt (see following text).

Other patients have excessive pulmonary blood flow, as they have little or no obstruction between the heart and pulmonary artery (Chapter 7). The high pulmonary vascular resistance present at birth usually prevents symptomatic pulmonary overcirculation in the neonatal period. However, as the resistance decreases over the first few weeks of life, pulmonary blood flow increases, and the patient develops tachypnea, diaphoresis, and poor feeding associated with congestive heart failure. These infants may not appear cyanotic, as the large pulmonary blood flow may result in saturations >85%. Seldom, however, will the oxygen saturation be >95%, and a pO in 100% oxygen almost always will be <100 mm Hg. Placement of a pulmonary artery band may be indicated (Chapter 7). Alternatively, some surgeons prefer to ligate the pulmonary artery and place a shunt with a goal of more precise control of pulmonary blood flow.

The overall goal of therapy for patients with a functional single ventricle is to divide the output of the single ventricle between the systemic and pulmonary vascular beds such that systemic oxygen delivery is adequate and the volume load to the functional single ventricle is minimized. Assuming a normal systemic output and normal pulmonary venous saturation, a systemic arterial saturation of 75% to 85% reflects a ratio of pulmonary to systemic flow of between 1:1 and 2:1. The hematocrit should be at least 40% to 45% to assist in maintaining adequate systemic oxygen delivery in the presence of moderate hypoxemia. Ferrous sulfate should be administered to most infants with this circulation because of their greater hematopoietic needs.

Rationale for Modified Fontan Operation

Before the 1970s, patients who received either a shunt or a pulmonary artery band as a neonate often developed ventricular failure in part because the functional single ventricle pumped blood to both the systemic and the pulmonary circulations. In addition, they were at risk for cerebrovascular accidents and brain abscesses because of right-to-left shunting. The average life span for these patients was 15 to 25 years of age.

The principle of the modified Fontan operation is that systemic venous return (superior and inferior vena caval blood) flows passively to the pulmonary arteries through surgically constructed anastomoses. The pulmonary venous return flows into the functional single ventricle and then is pumped to the aorta. Thus, the pulmonary and systemic circulations are completely separate (except for coronary venous return, which continues to drain into the heart via the coronary sinus) and flow in series. The patient is acyanotic and theoretically not at risk of paradoxical emboli. In addition, the functional single ventricle is pumping to one, not to two, circulations and is thus considered “volume unloaded.”

Characteristics of a Good Candidate for a Modified

Fontan Operation

Careful patient preparation and selection are critically important to attain a good long-term result after this procedure. From the time of initial diagnosis in the newborn period, it is incumbent on cardiologists and surgeons to be aware of the following considerations when planning treatment of patients with functional single ventricles:

• For blood to flow passively to the pulmonary arteries, the pulmonary arteries must be well developed and the pulmonary artery pressures and resistances must be within normal limits. Distortion of the pulmonary arteries at the time of surgery must be avoided, and congenital stenoses should be relieved to allow proper growth and development of the pulmonary arterial vasculature.

• The function of the single ventricle must be within normal limits. If the end-diastolic pressure of the ventricle is increased (which is transmitted to the pulmonary vascular bed), passive pulmonary blood flow will be limited, resulting in cyanosis and poor cardiac output. Thus, prolonged volume loading and outflow obstruction must be avoided.

• There should be no or only mild atrioventricular valve regurgitation. Moderate or more severe degrees of regurgitation will increase left atrial pressure, which in turn increases pulmonary pressures, therefore limiting pulmonary blood flow. Minimizing the volume load to the ventricle decreases the risk of atrioventricular valve regurgitation.

• Aorto-pulmonary collaterals vessels increase the volume load to the functional single ventricle and should be ligated, coiled, or unifocalized with the true pulmonary arteries.

The modified Fontan operation was originally performed all at one operation; that is, the venous return through both the superior and the inferior vena cavae was directed to the pulmonary arteries. This procedure was often associated with considerable morbidity. Additionally, patients seem to have a better long-term outcome when their single ventricle is volume unloaded at a relatively early age. It is not usually practical to perform the Fontan operation on patients <12 to 18 months of age. For these reasons, the modified Fontan operation is usually separated into two stages.

Superior Cavopulmonary Anastomosis

The first stage toward a modified Fontan circulation is a superior cavopulmonary anastomosis, which can be performed in a patient as young as 4 to 6 months of age.

FIGURE 6-13. Superior cavopulmonary anastomosis. The superior vena cava is anastomosed to the right pulmonary artery. Abbreviations: IVC, inferior vena cava; LPA, left pulmonary artery; RA, right atrium; RPA, right pulmonary artery; SVC, superior vena cava.

This current approach is a modification of the original Glenn shunt (end-to-end anastomosis of the superior vena cava to the right pulmonary artery) and is sometimes referred to as a bidirectional Glenn shunt. However, most centers have further modified the procedure so that the term “superior cavopulmonary anastomosis” is more accurate. Typically, the superior vena cava is divided, and the cephalic end is connected end to side to the ipsilateral pulmonary artery (Figure 6-13). If a patient has bilateral superior vena cavae, then bilateral superior cavopulmonary anastomoses are performed. A variation in surgical technique, called a hemi-Fontan, is preferred by some surgeons. The hemi-Fontan does not divide the superior vena cava but excludes inferior vena caval blood from the pulmonary arteries by means of a temporary intra-atrial patch.

Modified Fontan Operation

Most patients will have had a superior cavopulmonary anastomosis (or hemi-Fontan) as a first stage of the Fontan procedure (an initial palliation, either a shunt or a modified Norwood procedure, discussed in Chapter 8, usually precedes the first stage). The modified Fontan operation is performed anywhere from 1 to 3 years later. The goal of this procedure is to direct flow from the inferior vena cava to the pulmonary arteries. The exact method by which the modified Fontan operation is performed depends on the patient’s anatomy and the preference of the physicians. This may involve a right atrial to pulmonary arterial anastomosis, a lateral tunnel in which a baffle is created within the atrium to direct the inferior vena caval blood flow to the pulmonary artery, or an extracardiac conduit (Figure 6-14). Many believe that creation of a fenestration within the Fontan circuit (the fenestration functions physiologically like an atrial septal defect) decreases the morbidity associated with the procedure. Some fenestrations close spontaneously; whether the fenestration that remains open should be closed is unknown.

Long-term outcome studies have shown that patients who have undergone successful modified Fontan operations live longer than those who were treated with shunts and/or pulmonary arterial banding. Most surviving patients are in New York Heart Association Class I-II. Their exercise capacity is about 60% of normal. However, the modified Fontan operation is a less-than-perfect solution to the complex problem of functional single ventricle. Some of these patients are reasonably asymptomatic, but many eventually develop atrial arrhythmias, intracardiac thromboses, protein-losing enteropathy, and/or significant ventricular dysfunction. Some eventually require cardiac transplantation.

Damus-Kaye-Stansel Operation

This procedure is performed primarily for patients with functional single ventricle in whom the aorta arises from a hypoplastic ventricular chamber that has a small communication (bulboventricular foramen) with a functional single ventricle. These patients thus have the equivalent of subaortic stenosis. Resection of the ventricular septum is associated with high morbidity and mortality. For this reason, as shown in Figure 6-15, a connection is placed between the main pulmonary artery and the ascending aorta. The pulmonary valve and proximal main pulmonary artery becomes the main outlet to the systemic circulation. Depending on the exact anatomy, the connection can be a tube graft as shown or a patch that creates a side- to-side anastomosis when the aorta and pulmonary artery are close to each other. Flow to the pulmonary arteries is supplied by a shunt.

FIGURE 6-14. Diagram of a modified Fontan operation showing a bidirectional Glenn shunt and an extracardiac conduit. MPA indicates main pulmonary artery.

FIGURE 6-15. Damus-Kaye-Stansel procedure. A small communication between the left and right ventricles creates physiologic subaortic stenosis. In this example, a tube graft has been placed between the main pulmonary artery and ascending aorta to provide unobstructed blood flow to the systemic circulation (PA-AO anatomosis). The pulmonary artery is ligated distally, and pulmonary blood flow is supplied by a systemic-to-pulmonary artery shunt. Abbreviations: Ao, aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; RA, right atrium.

SUGGESTED READINGS

General

Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. Vol. 2. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:chaps 38-43, 49-53.

Hoffman JIE. The Natural and Unnatural History of Congenital Heart Disease. Oxford, England: Wiley-Blackwell; 2009:chaps 3-6, 39-43, 46.

Moller JH, Hoffman JIE, eds. Pediatric Cardiovascular Medicine. 2nd ed. Philadelphia, PA: Churchill Livingstone; 2012:chaps 14, 33, 35, 36, 39-44.

Rudolph AM. Congenital Diseases of the Heart: Clinical- Physiological Considerations. Chichester, England: Wiley- Blackwell; 2009:chaps 14-18.

Defects With Decreased Pulmonary Blood Flow

Cohen MS, Anderson RH, Cohen MI, et al. Controversies, genetics, diagnostic assessment, and outcomes relating to the heterotaxy syndrome. Cardiol Young. 2007;17(suppl 2): 29-43.

da Silva JP, Baumgratz JF, da Fonseca L, et al. The cone reconstruction of the tricuspid valve in Ebstein’s anomaly. The operation: early and midterm results. J Thorac Cardiovasc Surg. 2007;133:215-223.

Daubeney PE, Delany DJ, Anderson RH, et al. Pulmonary atresia with intact ventricular septum: range of morphology in a population-based study. J Am Coll Cardiol. 2002; 39:1670-1679.

Jacobs JP, Franklin RC, Wilkinson JL, et al. The nomenclature, definition and classification of discordant atrioventricular connections. Cardiol Young. 2006;16(suppl 3): 72-84.

Rosenthal E, Qureshi SA, Chan KC, et al. Radiofrequency- assisted balloon dilatation in patients with pulmonary valve atresia and an intact ventricular septum. Br Heart J. 1993;69:347-351.

Schmidt KG, Cloez JL, Silverman NH. Changes of right ventricular size and function in neonates after valvotomy for pulmonary atresia or critical pulmonary stenosis and intact ventricular septum. J Am Coll Cardiol. 1992;19:1032-1037.

Shinkawa T, Polimenakos AC, Gomez-Fifer CA, et al. Management and long-term outcome of neonatal Ebstein anomaly. J Thorac Cardiovasc Surg. 2010;139:354-358.

Wald RM, Adatia I, Van Arsdell GS, Hornberger LK. Relation of limiting ductal patency to survival in neonatal Ebstein’s anomaly. Am J Cardiol. 2005;96(6):851-856.

d-Transposition Complexes

Griselli M, McGuirk SP, Ko CS, et al. Arterial switch operation in patients with Taussig-Bing anomaly—influence of staged repair and coronary anatomy on outcome. Eur J Cardiothorac Surg. 2007;31:229-235.

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Leobon B, Belli E, Ly M, et al. Left ventricular outflow tract obstruction after arterial switch operation. Eur J Cardiothorac Surg. 2008;34:1046-1050.

Pasquali SK, Hasselblad V, Li JS, et al. Coronary artery pattern and outcome of arterial switch operation for transposition of the great arteries: a meta-analysis. Circulation. 2002;106:2575-2580.

Sakata R, Lecompte Y, Batisse A, et al. Anatomic repair of anomalies of ventriculoarterial connection associated with ventricular septal defect. I. Criteria of surgical decision. J Thorac Cardiovasc Surg. 1988;95:90-95.

Palliative Procedures

Alwi M, Choo KK, Latiff HA, et al. Initial results and medium-term follow-up of stent implantation of patent ductus arteriosus in duct-dependent pulmonary circulation. J Am Coll Cardiol. 2004;44:438-445.

Anderson PAW, Sleeper LA, Mahony L, et al. Contemporary outcomes after the Fontan procedure: a pediatric heart network multicenter study. J Am Coll Cardiol. 2008;52:85-98.

Blaufox AD, Sleeper LA, Bradley DJ, et al. Functional status, heart rate, and rhythm abnormalities in 521 Fontan patients 6 to 18 years ofage. J Thorac Cardiovasc Surg. 2008;136:100-107.

Cowgill LD. The Fontan procedure: a historical review. Ann Thorac Surg. 1991;51:1026-1030.

Giardini A, Hager A, Pace Napoleone C, et al. Natural history of exercise capacity after the Fontan operation: a longitudinal study. Ann Thorac Surg. 2008;85:818-821.

Khairy P, Poirier N, Mercier LA. Univentricular heart. Circulation. 2007;13:800-812.

McCrindle BW, Williams RV, Mitchell PD, et al. Relationship of patient and medical characteristics to health status in children and adolescents after the Fontan procedure. Circulation. 2006;113(8):1123-1129.

Murphy AM, Cameron DE. The Blalock-Taussig-Thomas collaboration: a model for medical progress. JAMA. 2008;300:328-330.