■ INTRODUCTION
■ PATHOPHYSIOLOGY OF INCREASED PULMONARY BLOOD FLOW
Clinical Presentation
Pathophysiology of Tachypnea
Classification of Defects That Result in
Increased Pulmonary Blood Flow
■ LEFT-TO-RIGHT SHUNTS
Atrioventricular Septal Defect
Ventricular Septal Defect
Aorto-Pulmonary Window/Anomalous
Origin of One Pulmonary Artery From the Ascending Aorta
Patent Ductus Arteriosus Arteriovenous Malformation
■ DEFECTS WITH BIDIRECTIONAL SHUNTS AND EXCESSIVE PULMONARY BLOOD FLOW
Total Anomalous Pulmonary Venous Connection Without Obstruction
Single-Ventricle Physiology Without Outflow Obstruction
Truncus Arteriosus
■ PULMONARY ARTERY BAND
■ SUGGESTED READINGS
■ INTRODUCTION
Respiratory distress in the setting of normal peripheral perfusion and without overt cyanosis is the least common manifestation of symptomatic cardiovascular disease in the newborn. Particularly in the absence of a murmur, the diagnosis of heart disease is often delayed or missed entirely because respiratory distress alone in an acyanotic infant with normal perfusion is most often caused by lung disease rather than intrinsic cardiac disease. Furthermore, symptoms usually develop gradually over the first few days or weeks of life, and the respiratory symptoms, such as tachypnea with feeding, are often subtle. It may take several weeks or more to recognize that the infant is growing poorly and that heart disease may be the cause. This chapter reviews structural cardiovascular defects that can cause respiratory distress with normal systemic perfusion; obstructive structural heart disease is discussed in Chapter 8; cardiomyopathies and arrhythmias are discussed in Chapters 9 and 10, respectively; and heart failure is discussed in Chapter 11.
■ PATHOPHYSIOLOGY OF INCREASED PULMONARY BLOOD FLOW
Clinical Presentation
A diverse group of congenital structural cardiovascular defects share the common feature of increased pulmonary blood flow as the main pathophysiologic process. It is this common characteristic that is the basis for the majority of signs and symptoms caused by this group of defects. The arterial oxygen saturation, although sometimes mildly decreased, is not so low that either cyanosis is present or systemic oxygen delivery is compromised.
The primary symptom in these infants is tachypnea, often accompanied by mildly increased work of breathing. In addition to tachypnea, many of these infants exhibit other signs and symptoms of the heart failure syndrome (Chapter 11). These infants have heart failure with high cardiac output (“high-output failure”), which is very different than the low-output failure that occurs in adults with acquired heart disease and in neonates with decreased systemic perfusion (Chapters 8 and 11). In addition to increased pulmonary blood flow, systemic blood flow is often increased in response to the increased metabolic demands resulting from the greater respiratory effort. The increased cardiac output leads to greater circulating blood volume to maintain normal filling pressures. The heart is hypercontractile, and systemic and pulmonary venous filling pressures are usually normal. Peripheral edema does not occur because venous pressures are not increased. However, hepatomegaly is a fairly constant finding because the liver and hepatic veins are very compliant and enlarge to accommodate the increased circulating blood volume.
Oxygen consumption, or metabolic demand, is increased for a variety of reasons. The major contributor is the increased work of breathing. In a normal infant, breathing is a large component of basal oxygen consumption (20%), which is similar to the metabolic requirements for growth. As the work of breathing increases, it may comprise 30% to 40% of oxygen consumption. An increase in adrenergic drive is necessary to maintain the increased combined ventricular output, and this too increases oxygen consumption, particularly by stimulation of brown fat metabolism. This increased adrenergic drive is mediated by both neural and hormonal mechanisms and causes two other common signs of high-output heart failure: tachycardia and diaphoresis. In infants, diaphoresis is observed on the forehead and scalp, especially during feeding.
Finally, failure to thrive is an important and frequent component of the clinical presentation. It is caused by the increased caloric requirements associated with increased oxygen consumption and by decreased caloric intake. These infants feed poorly because of their increased respiratory effort; they vomit frequently because of gastroesophageal reflux in the presence of increased intraabdominal pressure, which in turn is caused by increased respiratory effort. The caloric intake required for growth in a normal infant is about 100 to 120 kcal/kg/d. Failure to thrive occurs because the infant in high-output failure may take in only a fraction of this amount. These infants may require 160 to 180 kcal/kg/d to maintain a normal growth rate because of increased metabolic demands.
Pathophysiology of Tachypnea
The mechanism for tachypnea in infants with increased pulmonary blood flow is not known. Left atrial pressures are generally normal. Ventilation and oxygenation also are not impaired, which indicates that significant alveolar edema is not present. The increased amount of fluid in the thorax caused by increased pulmonary blood flow, particularly distributed in the pulmonary veins, may make it more difficult for the infant to breathe by increasing the weight of the lungs, but this has never been shown to be an independent factor in respiratory work. More likely, the increased production of interstitial fluid with the attendant increase in lymphatic flow is the primary cause of tachypnea in these infants.
As blood flows normally through the lungs, interstitial fluid is produced. This fluid is drained from the interstitial spaces by the lymphatic vessels. As blood flow increases, lymphatic flow increases similarly. Defects with high pulmonary arterial pressures increase precapillary pressures, which further increase lymphatic flow. As interstitial fluid production increases, the ability of the lymphatics to drain the fluid may be exceeded, causing accumulation of interstitial fluid. The fluid is predominantly peribronchial, which may impair bronchial function. Airway size may decrease, and airway resistance may increase, further increasing the work of breathing. In addition, the infant may be more likely to develop wheezing, as only a small further decrease in airway lumen would impair air exchange. This scenario explains not only the tachypnea universally seen in infants with a symptomatic increase in pulmonary blood flow but also the radiographic findings of increased vascular markings, the presence of peribronchial edema, and other manifestations of interstitial but not of alveolar fluid. It also explains why some of them (especially those without murmurs) initially are diagnosed as having bronchiolitis.
Infants with normal lung size and function and no abnormalities other than cardiovascular disease do not develop tachypnea and failure to thrive until pulmonary blood flow is very high, usually exceeding two and a half times the normal flow. The onset of symptoms tends to track with the time course over which pulmonary blood flow increases after birth. In the normal infant, systemic blood flow peaks at around 6 to 10 weeks of age, at the time of the nadir of hemoglobin concentration. Pulmonary vascular resistance also decreases during this time period. Thus, pulmonary blood flow increases greatly during this time in the infant with a cardiovascular defect associated with increased pulmonary blood flow—there is an increase in systemic blood flow associated with physiologic anemia concomitant with an increase in the relative proportion of blood flow to the lungs (an increased pulmonary-to-systemic blood flow ratio) because of the decreased pulmonary vascular resistance.
In contrast, infants with intrinsic pulmonary disease who also have excessive pulmonary blood flow may develop tachypnea and heart failure at a level of pulmonary blood flow that is only modestly higher than normal. A common situation is an infant born prematurely who develops bronchopulmonary dysplasia. The presence of even a minor cardiac structural defect (such as an atrial septal defect) that would not cause symptoms in a normal-term infant may result in significant symptoms in this setting. The onset of symptoms and the requirement for medical and/or surgical intervention are often accelerated in this subset of infants.
Classification of Defects That Result in Increased Pulmonary Blood Flow
Many congenital cardiovascular defects cause an increase in pulmonary blood flow as the dominant pathophysiological process, yet some are categorized according to other manifestations that are of less importance with regard to the clinical presentation. Truncus arteriosus and total anomalous pulmonary venous connection without obstruction are good examples. Because some degree of systemic arterial desaturation occurs in both of these conditions, they are often classified as “cyanotic heart disease.” However, in contrast to classical cyanotic defects (such as d-transposition of the great arteries and tetralogy of Fallot), truncus arteriosus and total anomalous pulmonary venous connection without obstruction are associated with only modest systemic arterial desaturation that may not be recognized visually. Furthermore, the predominant symptoms are tachypnea and failure to thrive, which are secondary to excessive pulmonary blood flow, not cyanosis. These defects should therefore be categorized among those that cause excessive pulmonary blood flow rather than cyanosis.
Defects that cause excessive pulmonary blood flow can be divided into two distinct subgroups. In both subgroups, excessive pulmonary blood flow occurs because a large volume of saturated pulmonary venous blood is diverted back into the pulmonary arteries via an abnormal communication (ie, a large left-to-right shunt is present). In the first subgroup, only a left-to-right shunt is present. No desaturated systemic venous blood is diverted into the systemic arterial bed. Thus, systemic arterial saturation is normal and equals that in the pulmonary veins (Figure 7-1). The second subgroup of defects also has a large left-to-right shunt but is distinguished by the additional presence of a right-to-left shunt; that is, systemic venous blood is diverted back into the systemic arterial circulation before passing through the pulmonary arterial system (Figure 7-2). Thus, some degree of systemic arterial desaturation is present in these infants. However, the dominant (or net) shunt is still left to right. Pulmonary blood flow is markedly increased, and systemic blood flow is normal or mildly increased. Consequently, the extent of systemic arterial desaturation is only modest, and the clinical effects of that desaturation are negligible.
These principles are illustrated by considering an infant with truncus arteriosus with the following scenario: (1) all systemic and pulmonary venous blood mixes completely in the combined outflow tract so that aortic and pulmonary arterial blood oxygen saturations are the same, (2) pulmonary blood flow has increased to four times the systemic normal blood flow after 1 week of life, (3) pulmonary venous blood is nearly fully saturated at 98%, and (4) systemic venous blood is less saturated than normal, at 50%, because of the increased respiratory work and decreased systemic arterial saturation. Therefore, four volumes of pulmonary venous blood mix with one volume of systemic venous blood in the ventricular outflow, and that blood is ejected out the aorta and pulmonary arteries. When these five volumes of blood mix, the oxygen saturation of the fully mixed blood is
Thus, this infant has a systemic arterial saturation of about 88%. Moreover, the systemic arterial saturation in such an infant is even higher because of preferential flow of left ventricular blood anteriorly and rightward, toward the ascending aorta (see discussion of truncus arteriosus below). The infant may not appear cyanotic because the threshold for observing cyanosis is about 85% with a normal hemoglobin concentration and is even lower at a few weeks of age because of the normal physiologic anemia. In addition, oxygen delivery to the tissues is not impaired because normally only about 25% of the oxygen delivered is consumed. Tachypnea is a prominent manifestation because of high pulmonary blood flow, and failure to thrive would be present for the reasons described earlier. Thus, categorizing such an infant as having “cyanotic heart disease” is not consistent with either the physical examination or the pathophysiology of the defect. Instead, categorizing truncus arteriosus as a defect with “excessive pulmonary blood flow” is more appropriate on both accounts.
FIGURE 7-1. Exclusive left-to-right shunt. In this diagram of a ventricular septal defect, much of the fully saturated pulmonary venous blood (PV) passes through the ventricular septal defect to join the poorly saturated systemic venous blood (SV). This left-to-right shunt increases the saturation of pulmonary arterial blood (PA) above systemic venous saturation. However, none of the systemic venous blood crosses the ventricular septal defect to enter the aorta. Thus, the oxygen saturation of systemic arterial blood (SA) is normal and equal to that in the pulmonary veins.
Infants with excessive pulmonary blood flow can therefore be categorized as having an exclusive left-to- right shunt or as having bidirectional shunting but with a dominant left-to-right shunt. Within each category, the defects can be considered according to the anatomic level, beginning arbitrarily with left-to-right shunts that empty into the right atrium and progressing through the right ventricle, pulmonary arteries, and the systemic veins (Tables 7-1 and 7-2).
FIGURE 7-2. Predominant left-to-right shunt with an associated right-to-left shunt. In this idealized diagram of total anomalous pulmonary venous connection, the large volume of fully saturated pulmonary venous blood (PV) fully mixes in the right atrium with the smaller volume of systemic venous blood (SV). The majority of this fully mixed blood passes into the right ventricle to enter the pulmonary artery, and a lesser amount crosses the foramen ovale to the left side of the heart and into the aorta. Thus, pulmonary arterial (PA) and systemic arterial blood (SA) have the same oxygen saturation, which is determined by the relative volumes of pulmonary venous and systemic venous blood flows.
TABLE 7-1. Congenital Cardiovascular Malformations That Result in an Exclusive Left-to-Right Shunt. Defects in Bold Letters Commonly Cause Symptoms During the Neonatal Period.
|
Anatomic level |
Structural defect |
|
Atrial septum |
Secundum atrial septal defect Primum atrial septal defect Sinus venosus atrial septal defect |
|
Atrioventricular septum |
Complete atrioventricular septal defect Partial atrioventricular septal defect |
|
Ventricular septum |
Inlet ventricular septal defect Perimembranous ventricular septal defect Muscular ventricular septal defect (may cause symptoms if a large mid-muscular defect is present) Outlet ventricular septal defect |
|
Truncal/aortopul- monary septum |
Aortopulmonary window Anomalous origin of the right pulmonary artery from the ascending aorta |
|
Arterial communication |
Patent ductus arteriosus Arteriovenous malformation |
|
Venous communication |
Partial anomalous pulmonary venous connection |
■ LEFT-TO-RIGHT SHUNTS
This section will consider only congenital cardiovascular defects with exclusive left-to-right shunts that cause symptoms in the otherwise normal infant. Several defects associated with left-to-right shunting will not be considered because they do not cause symptoms. For example, left-to-right shunting across an atrial septal defect occurs when the stiffness of the left ventricle is greater than that of the right ventricle. Newborn infants have a right ventricle that is of equal or greater thickness and stiffness as the left ventricle so that the left-to-right shunt at birth is small or nonexistent (Chapter 3). Although pulmonary vascular resistance begins to fall immediately at birth, it takes months for the right ventricle to remodel and accept a significantly greater amount of blood than the left ventricle. In addition, pulmonary arterial pressures are normal so that less interstitial fluid is produced for the same level of pulmonary blood flow. Thus, unless the infant has lung disease, even a large atrial septal defect does not cause symptoms in newborns and young infants.
At the atrioventricular and ventricular levels (eg, a ventricular septal defect), the magnitude of the left- to-right shunt increases much more rapidly after birth. These shunts depend on the relative resistances of the pulmonary and systemic vascular beds. The shunt occurs almost exclusively in systole when the distal vascular bed (the resistance vasculature) is filled with blood from the previous contraction, which limits the extent of the shunt. Although pulmonary vascular resistance falls precipitously immediately after birth, it does not fall so low that a systolic shunt will be large enough to cause symptoms. The further steady decline in pulmonary vascular resistance over the next several weeks of life occurs simultaneously with the normal decline in hemoglobin and hematocrit (physiologic “anemia” of infancy). Together, these processes promote a progressive increase in left-to- right shunting and pulmonary blood flow to levels high enough to cause symptoms. Typically, symptoms are noted between 4 and 8 weeks of age. An exception is a small number of infants with an atrioventricular septal defect who have a direct communication between the left ventricle and the right atrium or severe mitral insufficiency. Both of these conditions lead to a large atrial left-to-right shunt; the shunt is obligatory in that atrial pressure is always much lower than left ventricular pressure during ventricular systole. In these neonates, a very large left-to-right shunt may develop within the first days after birth, causing early symptoms of heart failure.
|
TABLE 7-2. Congenital Cardiovascular Malformations With Bidirectional Shunts and Excessive Pulmonary Blood Flow |
|
|
Anatomic level |
Structural defect |
|
Atrial septum |
Common atrium (usually left atrial isomerism) |
|
Atrioventricular septum |
Complete atrioventricular septal defect with common ventricle (usually left atrial isomerism) |
|
Ventricular septum |
Single ventricle physiology: 1. Double-inlet left ventricle (usually l-malposed aorta) and unobstructed outflow tracts 2. AV valve atresia/stenosis (mitral or tricuspid) with large ventricular septal defect and unobstructed outflow tracts |
|
Truncal/ aortopulmonary septum |
Truncus arteriosus |
|
Venous communication |
Total anomalous pulmonary venous connection without obstruction |
At the arterial level (eg, a patent ductus arteriosus), the shunt occurs during both systole and diastole. Diastolic shunts are always much larger than the corresponding systolic shunt because blood continues to flow from the resistance vessels of the lungs during diastole, affording much more vascular space to be filled. Thus, shunts at the arterial level are likely to cause high-output heart failure at an earlier age than shunts that occur at the ventricular level. These infants are frequently tachypneic when they leave the hospital after birth, but it may not be appreciated until they return for postnatal follow-up and are found to be failing to thrive.
If there is a large connection at the ventricular or arterial level, pulmonary arterial systolic pressure is equal to that in the aorta; these defects are considered “nonrestric- tive.” If the amount of shunting is limited by the size of the connection, pulmonary arterial systolic pressures are less than systemic, and the defect is considered “pressure restrictive.” It is important to be aware that a pressure- restrictive connection can have a large amount of flow across it.
The presence of elevated pressures in the pulmonary vascular bed alters the normal regression of pulmonary arterial musculature. In the fetus and newborn, the small pulmonary arteries have a thicker medial smooth muscle layer in relation to diameter than similar arteries in adults. Birth is normally associated with a marked relaxation of these vessels, leading to a large decrease in pulmonary vascular resistance and increase in pulmonary blood flow (Chapter 3). The high pulmonary arterial pressures resulting from a nonrestrictive defect prevent regression of this muscle. In addition, increased blood flow in the presence of elevated pressures creates shear forces on the distal pulmonary arteries and arterioles, which, if uncorrected, can lead to irreversible damage to these vessels (pulmonary vaso-occlusive disease). This occurs over the first few years of life, more rapidly in the unrestrictive arterial level shunt (eg, ductus arteriosus) because pressure is increased not only in systole, as occurs in a ventricular level communication, but also during diastole.
Shunts that occur at an arteriovenous level (eg, a congenital arteriovenous malformation) are also obligatory shunts because, even in the fetus, arteriolar pressure far exceeds venous pressure. Thus, the magnitude of the shunt is directly related to the size of the malformation, and the transition from fetus to newborn or newborn to older infant does not alter the magnitude of the shunt. The difference in compliance of the two vascular beds is so great that any increase in ventricular output merely passes into the systemic veins.
Finally, exclusive left-to-right shunts at a pulmonary venous level (eg, partial anomalous pulmonary venous connection) drain into the right atrium or systemic veins. Partial anomalous pulmonary venous return presents similarly to an atrial septal defect, and it may take several months for a clinically significant shunt to develop, if ever.
Atrioventricular Septal Defect
Anatomic and Physiologic Considerations
Atrioventricular septal defects are often termed “endocardial cushion defects” or “atrioventricular canal defects,” but these terms assume an understanding of the embryologic origin, which has yet to be completely defined. The spectrum of defects that make up atrioventricular septal defects, from the primum atrial septal defect and the cleft mitral valve to the complete atrioventricular septal defect, have one common finding: absence of the atrioventricular septum (Figure 7-3). Thus, the term “atrioventricular septal defect” seems most appropriate. The septal leaflet of the tricuspid valve inserts inferiorly to the septal attachments of the mitral valve, and it is the atrioventricular septum that separates the right atrium from the left ventricle. This portion of the septum is very small and is recognized on echocardiography by the more inferior hinge point of the septal leaflet of the tricuspid valve compared to the anterior leaflet of the mitral valve. In all forms of atrioventricular septal defect, this discrepancy is absent, and the two valves lie in the same plane. Because of the absence of the atrioventricular septum, it is possible for blood to shunt directly from the left ventricle to the right atrium. As stated in the preceding discussion, this type of shunt is obligatory and can be quite large. However, the atrioventricular valve tissue usually prevents such a direct connection, and in most cases of atrioventricular septal defects, a left ventricle-to-right atrium shunt is not present.
FIGURE 7-3. A. Apical four-chamber echocardiogram in a normal newborn infant. The atrioventricular septum (avs) lies between the medial hinge point of the mitral valve (mv) and the more inferiorly placed septal hinge point of the tricuspid valve (tv). B. Apical four-chamber echocardiogram in a newborn infant with a complete atrioventricular canal defect. Note that the right-sided component of the atrioventricular valve (ravv) hinges at the same level as the left-sided component (lavv) so that there is no atrioventricular septum. The absence of an atrioventricular septum occurs even in the presence of a partial atrioventricular canal defect (eg, a primum atrial septal defect) in which there is no ventricular septal defect. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
Clinical Presentation
A complete atrioventricular septal defect does not usually cause symptoms in the fetal or early neonatal periods. Newborn infants may not have a cardiac murmur because pulmonary vascular resistance is still relatively high. This is an especially important consideration in a newborn with trisomy 21, in whom the likelihood of an atrioventricular septal defect is high. The absence of a murmur is common in these infants because they frequently have lung hypoplasia, which contributes to the maintenance of high pulmonary vascular resistance. Thus, every infant with trisomy 21, even in the absence of a murmur or other signs and symptoms, should have an echocardiogram reviewed by a pediatric cardiologist. Most infants with a complete atrioventricular septal defect present within the first few weeks of life with tachypnea, diaphoresis, poor feeding, and failure to thrive.
On physical examination, the weight percentile is usually at least one or two standard deviations below the length percentile. If the infant has trisomy 21, it is important to use growth charts specific to this condition, which show quite a different normal growth pattern than that of the normal population. There is often moderate resting tachycardia, in the range of 130 to 150 beats per minute. Tachypnea with intercostal and substernal retractions is common. The extremities are warm and well perfused, and the peripheral pulses are strong, indicating that systemic blood flow is well maintained by peripheral vasodilation. Systemic oxygen saturation measured by pulse oximetry may be normal at rest but may be in the low 90s, especially during crying, because of right-to-left shunting at the atrial level. The liver is moderately enlarged with a sharp margin, and splenomegaly can often be appreciated. The precordium is diffusely hyperactive to palpation. The first heart sound is often normal but occasionally may be louder than normal. If the atrial or ventricular-atrial shunt is large and there is a right bundle branch block, the second heart sound may be widely split with little variation. More often, however, the rapid heart rate and high pulmonary arterial diastolic pressures make it difficult to appreciate splitting of the second heart sound. However, the second heart sound is almost always louder than normal because of high diastolic pulmonary arterial pressure. Extra heart sounds are not common, but occasionally an S3 can be heard at the apex. There is often a harsh mid-frequency systolic murmur along the mid- sternal border that may be holosystolic and that radiates throughout the chest. A separate systolic murmur of higher frequency may be appreciated at the apex if there is significant left-sided atrioventricular (mitral) valve insufficiency. This situation should be suspected if the pulses are decreased and the peripheral extremities are cool. A diastolic inflow rumble is often present at the apex or the lower left sternal border, though rapid heart rates may make it difficult to appreciate. More often, the absence of silence in diastole suggests that a diastolic murmur is present. The diastolic murmur is caused by excessive blood flow across the mitral valve and usually indicates that pulmonary blood flow is at least twice the normal.
FIGURE 7-4. An electrocardiogram in an infant with a complete atrioventricular septal defect. The ECG shows left axis deviation (approximately -120 degrees) and right ventricular hypertrophy (a dominant R wave with upright T waves in V1 and deep S waves in V6).
Ancillary Tests
• The chest radiograph shows generalized cardiomegaly with a globular heart, often including a prominent right contour indicative of right atrial enlargement and increased pulmonary vascularity.
• The electrocardiogram shows left axis deviation (QRS axis between 0 and -120 degrees) with a counterclockwise loop. Right ventricular hypertrophy is demonstrated by persistence of upright T waves with prominent R waves in the right precordial leads (Figure 7-4). If a large ventricular shunt is present, the electrocardiogram shows biventricular hypertrophy, indicated by the presence of normal left-sided forces despite right ventricular hypertrophy. These left-sided forces are demonstrated by prominent S waves in the right precordial leads as well as left-sided forces (R waves) in V6 and in the inferior limb leads.
• The echocardiogram clearly shows the common atrioventricular valve with atrial and ventricular septal defects. The attachments of the valve, the relative size of the two ventricles, and the degree of atrioventricular valve insufficiency are critical elements of the echocardiographic examination. Associated defects commonly occur, particularly secundum atrial septal defects and patent ductus arteriosus. The most important commonly associated defects are subaortic stenosis and coarctation of the aorta because of their deleterious effects on systemic perfusion.
Therapeutic Considerations
Treatment of heart failure and failure to thrive are important elements of the medical management of infants with atrioventricular septal defects. However, because of the large left-to-right shunt and propensity for the early development of pulmonary vascular disease, it is important to plan for early surgical repair. Infants with complete atrioventricular septal defects generally undergo surgical repair in the second or third month of life, even in the absence of severe heart failure and failure to thrive. Repair in the first few months of life is associated with a more benign postoperative course and fewer problems related to residual pulmonary hypertension. Although several surgical techniques are utilized, the general approach involves closure of the atrial and ventricular septal defects and repair of the atrioventricular valve. Postoperatively, these infants may have residual atrioventricular valve insufficiency (or occasionally atrioventricular valve stenosis). However, the prognosis is favorable, and most infants and children are symptom free after surgical repair.
Ventricular Septal Defect
Anatomic and Physiologic Considerations
The most common congenital cardiac structural malformation is a ventricular septal defect. Ventricular septal defects are categorized according to their position within the septum (Figure 7-5). The most common ventricular septal defects occur in the membranous septum, the very small component of the ventricular septum where the aortic, mitral, and tricuspid valves attach and where there is no muscle in the septal wall. These defects extend from the membranous region in any direction and are thus commonly termed “perimembranous ventricular septal defects.” Most commonly, they extend toward the outlet of the ventricles. In this situation, the outlet septum may be normally aligned with the inlet septum, allowing for unobstructed flow of blood from each ventricle to its respective great vessel. Less commonly, the outlet septum may be malaligned with respect to the inlet septum. If there is anterior deviation of the outlet septum, the defect is then subaortic, and it is associated with subpul- monic and pulmonic valve stenosis (tetralogy of Fallot; see Chapter 6). If there is posterior deviation of the outlet septum, the defect is subpulmonic, and there is often associated subaortic stenosis and coarctation of the aorta (Figure 7-6).
FIGURE 7-5. Schematic diagram of the ventricular septum. The sites of common ventricular septal defects are shown.
FIGURE 7-6. Posterior maligned ventricular septal defect. With posterior malignment of the outlet septum, the ventricular septal defect is subpulmonic, and the aortic outflow tract is narrowed. This decreases flow in the ascending aorta in the fetus, leading to coarctation of the aorta. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
Defects of the ventricular septum may also be isolated to the inlet portion, where the ventricular component of atrioventricular septal defects occurs (Figure 7-3). A defect may occur in the muscular septum, where they are often multiple. Tiny defects located in the apex of the muscular septum are common at birth and almost always close spontaneously. The most superior defects lie above the crista supraventricularis and directly under both the aortic and the pulmonary valves and are termed “supracristal” or “doubly committed subarterial” ventricular septal defects. In this type of defect, the deficiency in the subvalvar region causes the noncoronary cusp of the aortic valve to not be properly suspended. This often results in prolapse of the noncoronary cusp into the defect, causing aortic insufficiency (but typically not in the neonatal period).
Clinical Presentation
An infant with an isolated ventricular septal defect is rarely symptomatic in the first weeks of life. Rather, if symptoms are to develop, they do so after a few weeks as the pulmonary vascular resistance falls and the hematocrit approaches its postnatal nadir.
The symptomatic infant with a ventricular septal defect presents similarly to the infant with an atrioventricular septal defect. The infant is tachycardic and tachypneic, often with retractions, though this may be a subtle finding. Oxygen saturation measured by pulse oximetry is normal. Pulses and perfusion are normal or sometimes increased because of the increased sympathetic drive. Hepatomegaly occurs in association with the increased biventricular output. The lungs are clear to auscultation. The precordium is hyperactive. Right ventricular pressure is not necessarily increased because a pressure-restrictive defect may still allow a large enough shunt to cause symptoms. A parasternal thrill is occasionally present if there is a pressure-restrictive defect with a high-velocity jet across the septum that is directed anteriorly toward the sternum. The first heart sound is normal, and the second heart sound depends on pulmonary arterial pressures. Splitting of the second heart sound is normal or may be decreased, and the pulmonic component is louder than normal if the pulmonary artery pressures are increased. However, it is often difficult to appreciate the splitting and quality of the second heart sound because the murmur is usually loud and holosystolic. The frequency of the murmur should be evaluated carefully; the higher the frequency of the murmur, the more pressure-restrictive is the defect. A mid-diastolic inflow murmur is usually present in the symptomatic infant because of the increased flow across the mitral valve. This finding indicates a large left-to-right shunt.
Ancillary Tests
• The chest radiograph shows cardiomegaly, but unlike the infant with an atrioventricular septal defect who also has an atrial-level shunt, chamber enlargement is confined to the left side of the heart. Increased vascular markings are also present.
• The electrocardiogram usually shows a normal axis unless there is pulmonary hypertension, which may cause right axis deviation. Prominent left ventricular voltages are often present, and the presence or absence of right ventricular hypertrophy depends on the amount of pressure restriction across the defect. Left atrial enlargement may be evident as a wide (greater than 3 mm) and often bifid P wave in lead II.
• The echocardiogram is used to define the location, size, and number of ventricular septal defects; the alignment of the outlet septum; and the presence of associated defects as discussed earlier. Doppler echocardiography is used to estimate right ventricular and pulmonary arterial pressures and the magnitude of the left-to-right shunt.
Therapeutic Considerations
The timing of and need for medical and surgical intervention in early infancy depends on the magnitude of the left-to-right shunt and severity of symptoms. Many infants with a small defect and minimal left-to-right shunt are asymptomatic and do not require any intervention. Small defects often resolve spontaneously during the first year or two of life (especially isolated defects located in the muscular septum). In contrast, infants with a large left-to-right shunt and failure to thrive despite adequate medical management require surgical repair in the first few months of life. The risks of surgical repair are low, and there is no advantage to delaying surgical correction in most infants with symptoms due to a large ventricular septal defect. However, it should be recognized that the normal postnatal decline in hemoglobin and hematocrit may temporarily aggravate symptoms of heart failure. Thus, it may be reasonable to continue medical management until the normal physiologic anemia of infancy has resolved in those infants with mild or moderate symptoms.
Beyond early infancy, the decision to close a ventricular septal defect depends not on the size of the shunt and associated failure to thrive but rather on the size of the defect and/or associated defects. When the ventricular septal defect approaches the size of the aortic root, the defect is no longer pressure restrictive. That is, right ventricular systolic pressure equals that in the left ventricle. The increased pressure is transmitted to the pulmonary arteries. In turn, pulmonary arterial hypertension creates excessive shear forces in the distal pulmonary vasculature. Initially, this delays the normal postnatal regression of muscle in the walls of the arterioles. Over time, intimal hyperplasia, fibrosis, and ultimately vascular occlusion occur. The progression from reactive pulmonary hypertension to irreversible pulmonary vaso-occlusive disease in a patient with ventricular septal defect usually takes at least 18 months, though the time frame may be shorter for patients with trisomy 21. A decision regarding closure of a nonrestrictive ventricular septal defect is usually made within 4 to 6 months so that the risk for vaso-occlusive disease is minimized.
Associated defects that lead the cardiologist to recommend surgical closure may develop over time, but these rarely occur during infancy. They include membranous subaortic stenosis, double-chamber right ventricle (in which anomalous muscle bundles develop and obstruct blood flow into the right ventricular outflow tract), aortic insufficiency (caused by prolapse of an aortic valve leaflet into the defect, most commonly seen in supracristal defects), and recurrent bacterial endocarditis.
Occasionally, a ventricular septal defect is closed surgically or by a transcatheter approach when the shunt remains large enough to cause left ventricular dilation but is not associated with pulmonary hypertension or other defects. Because of the propensity for ventricular septal defects to decrease in size over time, such defects are usually not closed before 5 years of age.
Aorto-Pulmonary Window/Anomalous Origin of One Pulmonary Artery From the Ascending Aorta
Anatomic and Physiologic Considerations
These two structural defects are rare, but because they are related embryologically and present similarly, they are discussed together. In both defects, a direct communication between the ascending aorta and at least one pulmonary artery is present. However, because there are two semilunar valves, the shunt is exclusively left to right (unlike that of truncus arteriosus, described in the following discussion). Aorto-pulmonary window results from a deficiency in septation of the aorto-pulmonary septum, which thereby allows for a variably sized communication between the ascending aorta and main pulmonary artery (Figure 7-7). It usually occurs midway between the semilunar valves and the bifurcation of the main pulmonary artery. This defect is thought to be embryologically distinct from persistent truncus arteriosus based on observations that aorto-pulmonary window is not associated with chromosome 22 microdeletion syndromes (such as DiGeorge syndrome), nor is ablation of the cardiac neural crest tissue in experimental models associated with an aorto-pulmonary window. In utero, an aorto-pulmonary window often causes no abnormalities in blood flow patterns, but if the left ventricle ejects a large portion of its output across the window and through the main pulmonary artery to the ductus arteriosus, interruption of the aortic arch may occur. Interestingly, aorto-pulmonary window is associated with type A interruption of the aortic arch (distal to the subclavian artery) rather than the much more common type B interruption (between the carotid and subclavian artery), which is the type seen in infants with chromosome 22 microdeletion syndrome.
FIGURE 7-7. Aorto-pulmonary window. There is a defect in the aorto-pulmonary septum so that the systemic and pulmonary arterial vascular beds are connected just above the semilunar valves. It is often associated with interrupted aortic arch, as in this diagram.
Anomalous origin of the right pulmonary artery from the aorta occurs more frequently than that of the left, but both are quite rare. Anomalous origin of the right pulmonary artery occurs in association with aorto-pulmonary window and with type A interruption of the aortic arch.
Although it has been called “hemitruncus,” this is a poor term because, as mentioned earlier, these defects are not embryologically related to persistent truncus arteriosus and two separate semilunar valves are present, a finding that excludes an abnormality of truncal septation. Anomalous origin of the left pulmonary artery can occur in isolation but is more commonly associated with tetralogy of Fallot and thus does not present similarly to aortopulmonary window.
Clinical Presentation
The infant with aorto-pulmonary window or with anomalous origin of the pulmonary artery from the ascending aorta is tachypneic very soon after birth, though it may not be recognized immediately. This is particularly true when no murmurs are present, which may occur because stenosis of the communication is uncommon so that blood flows in a laminar manner through defect and central vessels. Inevitably, the infant exhibits poor growth and respiratory distress. On physical examination, the infant is generally warm with normal perfusion of the extremities. A hallmark finding is that of bounding pulses. The lungs are clear to auscultation. The liver is moderately enlarged. The precordium is hyperdynamic, indicative of a hypertensive right ventricle. Infants with anomalous origin of the right pulmonary artery often have left pulmonary arterial pressures that exceed systemic pressures; right ventricular systolic pressure is suprasystemic. The first heart sound is normal, and the second heart sound is narrowly split or single and is louder than normal. A harsh systolic murmur is commonly present at the upper sternal border and radiates to one or both lung fields. Occasionally, the murmur is continuous and resembles that heard in an infant with a patent ductus arteriosus. A mid-diastolic murmur at the apex reflects the increased blood flow across the mitral valve resulting from the increased pulmonary blood flow.
Ancillary Tests
• The chest radiograph shows generalized cardiomegaly with a prominent main pulmonary artery and increased vascularity. Pulmonary edema may be present, particularly when there is an associated interruption of the aorta arch (Figure 7-8).
• The electrocardiographic findings are variable but usually show persistent right precordial upright T waves and prominent anterior forces beyond the first week of life, indicative of right ventricular hypertrophy. Often, there is evidence of biventricular hypertrophy. Left atrial enlargement may be present.
• The echocardiogram shows an enlarged left atrium and left ventricle. It is often difficult to appreciate that there is a communication of the ascending aorta with one or both pulmonary arteries unless this is considered in the differential diagnosis. Right ventricular hypertension is present. The aortic arch should be carefully evaluated for the presence of obstruction.
FIGURE 7-8. A chest radiograph in an infant with aortopulmonary window and interrupted aortic arch. The important findings include generalized cardiomegaly with a left ventricle-forming apex, a large main pulmonary artery, and passive congestion of the lungs. An endotracheal tube is present, and ECG monitoring leads are evident on the shoulders.
Therapeutic Considerations
These defects require surgical repair. It is important to intervene early to prevent pulmonary vascular disease. Repair of an aorto-pulmonary window is generally accomplished from a transaortic approach. It is important to correct any associated defects if present. There have been a few reports of catheter-based intervention to close an aorto-pulmonary window without the need for surgery. Surgical correction of an isolated anomalous pulmonary artery arising from the ascending aorta requires division of the pulmonary at its origin and reimplantation into the main pulmonary artery. This may be accomplished directly or may require augmentation with prosthetic, autologous, or heterologous material.
Patent Ductus Arteriosus
Anatomic and Physiologic Considerations
A patent ductus arteriosus is a common problem in prematurely born infants but is relatively uncommon in term newborn infants. Moreover, unless it is quite large, a patent ductus arteriosus rarely causes symptoms in a term infant. In the term infant, normal postnatal closure of the ductus arteriosus occurs in two stages. Immediately after birth, contraction of the medial smooth muscle causes functional closure, usually within 12 to 24 hours. Thereafter, infolding of the endothelium causes disruption of the internal elastic lamina and proliferation of the subintimal layers. Necrosis of these layers occurs, and as the mounds continue to enlarge, there is progressive replacement of muscle fibers with connective tissue, resulting in permanent closure and converting the ductus to a ligamentum arteriosus. This process usually takes about 2 to 3 weeks. In the preterm infant, the initial functional closure frequently does not occur, and the decrease in pulmonary vascular resistance over the first few days of life causes an increasing left-to-right shunt through the ductus.
The initial closure of the ductus arteriosus and its failure to close in premature infants has been the subject of many investigations. Patency of the ductus arteriosus is mediated by the perfusing oxygen concentration and the levels of prostaglandin E2 and I2, although other vasoactive substances, such as bradykinin and circulating catecholamines, may contribute. The immature ductus is very sensitive to the dilating effects of prostaglandins and much less sensitive to the vasoconstricting effects of oxygen. As the ductus matures in the later stages of gestation, it becomes much more sensitive to oxygen and much less so to prostaglandins. Thus, the large increase in oxygen concentration usually induces complete closure of the ductus arteriosus in the term infant, but this is not the case in the preterm infant. Moreover, prostaglandin levels decrease to a greater extent in the term infant, further promoting ductal closure. Because the pulmonary vascular musculature is less well developed in preterm infants, pulmonary vascular resistance is particularly low, and shunts of a large magnitude can develop rapidly. In addition, pulmonary capillary permeability may be greater, allowing for the production of more interstitial edema in response to a moderate increase in pulmonary blood flow. Furthermore, the immature alveoli may be more sensitive to the presence of increased fluid. Because of these factors, a moderate left-to-right shunt through a ductus arteriosus has a far greater effect on the lung function in a preterm infant than in a term infant.
The effects of a patent ductus arteriosus on the systemic circulation are also much more prominent and deleterious in the preterm infant. In a term infant with a patent ductus arteriosus, the left ventricle is capable of greatly increasing output in response to the increases in preload and sympathetic nervous system activity. Despite a very large shunt, systemic blood flow usually is maintained, and organ ischemia does not occur. In contrast, the left ventricle of the preterm infant is less capable of increasing its output. The ventricle is less compliant because of higher water content and less organized myocyte architecture. Therefore, end-diastolic volume cannot increase as much in response to an increase in pulmonary venous return, limiting the increase in stroke volume. End-diastolic pressure increases to a greater extent, contributing to alveolar edema. Additionally, resting heart rate is greater and near the level at which a further increase causes a decrease in stroke volume. For all of these reasons, systemic blood flow frequently falls in the premature infant with a large patent ductus arteriosus. This decrease in systemic blood flow may lead to serious consequences, including renal insufficiency, necrotizing enterocolitis, and intraventricular hemorrhage. Even the myocardium is susceptible to ischemia. Although coronary blood flow can increase greatly in response to stress, the very low diastolic pressures in the aorta of the preterm infant with a ductus arteriosus may not provide sufficient perfusion pressure to prevent subendocardial ischemia.
Clinical Presentation
A large ductus arteriosus in a preterm infant usually presents after a few days of age as the infant is recovering from respiratory distress syndrome. The earliest signs are often an increased need for respiratory support and increased arterial carbon dioxide levels due to alveolar edema. The widespread use of surfactant therapy has decreased the severity of respiratory distress syndrome, but symptoms of a patent ductus arteriosus tend to occur earlier. Surfactant promotes alveolar patency and therefore improves oxygenation, but pulmonary vascular resistance falls more rapidly. Pulses become more prominent, and the pulse pressure widens, often with diastolic pressures falling into the mid- to low 20s. The liver is enlarged. The precordial impulse is very prominent. The heart sounds are normal, and an S3 gallop is occasionally heard.
The murmur is not the usual continuous murmur in the left infraclavicular area that is classically described in older infants. Rather, the murmur in preterm infants is usually heard along the left sternal border and is predominantly systolic with limited diastolic spillover. There may be an associated mid-diastolic rumble at the apex, although the rapid heart rates in preterm infants make this difficult to appreciate.
Ancillary Tests
• The chest radiograph shows an enlarged left ventricle and left atrium and interstitial and alveolar edema.
• The electrocardiogram in the preterm infant with a large ductus arteriosus is usually normal because the presentation is rapid and there is little time for ventricular hypertrophy to develop. However, if the ductus persists, left atrial enlargement, as manifested by a wide P wave in lead II, and left ventricular hypertrophy, with prominent inferior and lateral R waves and flattening of the ST-T waves, may develop. Marked biventricular hypertrophy may be seen in older infants with a large patent ductus arteriosus.
• Echocardiography is essential for confirmation of the diagnosis and assessment of severity and the exclusion of other congenital anomalies. The left atrium and ventricle are enlarged, and there is often an associated left-to-right shunt across the foramen ovale. Pulsed and color Doppler echocardiography demonstrate the left-to-right shunt, which occurs primarily in diastole. Although the width of the color jet roughly estimates the diameter of the ductus arteriosus and the size of the left-sided chambers roughly estimate the size of the shunt, the magnitude and importance of the ductal shunt is best determined by evaluating flow in the systemic arteries. The presence and extent of retrograde flow in the descending aorta correlates with severity, as it reflects the amount of blood that is being directed away from the gastrointestinal tract and kidneys. These organ systems are primarily perfused in diastole and are most susceptible to ischemic damage.
Therapeutic Considerations
Treatment of preterm infants with indomethacin has dramatically altered the management of patent ductus arteriosus. Indomethacin is administered either prophylactically or after recognition of the presence of a patent ductus arteriosus. A number of different dosing regimens have been proposed, and local institutional practices vary.
The key features are early administration and repeat dosing over a 24-hour period. It is important to repeat the echocardiogram if there is any suspicion of failure of the ductus to close or if reopening is suspected after initial closure. Repeat courses of indomethacin can be administered, but if ductal patency persists and the infant remains symptomatic, many authorities recommend an aggressive approach to surgical ligation of the ductus. In many institutions, this is accomplished in the neonatal intensive care unit, thereby avoiding potential problems associated with transporting a sick premature infant to and from the operating room. Some centers are performing transcatheter closure in infants as small as 2 kg because of the availability of newer devices that can be delivered from a venous approach using small 4F sheaths or catheters. This is generally limited to the large, tubular ductus that has enough length (at least 6 to 8 mm) to contain the device within the ductus, preventing device-related obstruction of the aortic or left pulmonary artery.
Recent studies have suggested that other nonsteroidal anti-inflammatory drugs, such as ibuprofen, may be equally effective as indomethacin and may have fewer side effects. Acetaminophen, which inhibits prostaglandin synthesis via interaction at the peroxidase site of prostaglandin H2 synthetase rather than being a cyclooxygenase inhibitor, has also recently been studied with outcomes similar to that of ibuprofen. The studies of both agents are still fairly limited, and indomethacin remains the primary medical therapy at this time.
A patent ductus arteriosus in a full-term infant rarely causes significant symptoms. However, closure is recommended if the ductus remains patent past infancy. Outside the neonatal period, the ductus arteriosus is not responsive to indomethacin, and either a surgical or a catheterbased approach to closure is necessary. Occlusion of the ductus in the catheterization laboratory is generally performed as the treatment of choice in a term infant with a persistently patent ductus outside of the neonatal period.
Arteriovenous Malformation
Anatomic and Physiologic Considerations
A systemic arteriovenous malformation has the same pathophysiological effects on pulmonary blood flow as an intracardiac defect, such as ventricular septal defect. The excess portion of flow that enters the venous system through the abnormal arteriovenous malformation is directed through the right atrium, right ventricle, and pulmonary arteries. The magnitude of the increase in systemic venous flow can be sufficiently large to cause interstitial edema and symptoms of excessive pulmonary blood flow.
Before birth, a very large arteriovenous malformation may cause heart failure by reducing systemic perfusion and elevating venous pressures, leading to hydrops fetalis. An arteriovenous malformation commonly associated with hydrops occurs in the placental circulation and may not be appreciated after birth. The placenta should be carefully evaluated in all infants with hydrops of unknown etiology.
The most common site for arteriovenous malformations that present symptomatically in the newborn is deep within the brain. These typically drain into a large vein of Galen and are associated with abnormal brain development. In addition, an unusually high incidence of sinus venous atrial septal defects is present in infants with vein of Galen malformations. The next most common site of arteriovenous malformation is in the liver. These are often associated with hepatic hemangioendotheliomas.
Clinical Presentation
After birth, the excessive venous flow is directed into the lungs as the foramen ovale and ductus arteriosus close. Unlike other causes of exclusive left-to-right shunts, the amount of shunting is not dependent on the slower, second phase of the decrease in pulmonary vascular resistance that occurs during the first few weeks of life. Furthermore, the shunt magnitude is only minimally affected by the postnatal decline in hemoglobin and hematocrit. In the presence of a large arteriovenous malformation, very high levels of pulmonary blood flow occur almost immediately after birth, and tachypnea can be apparent within hours. Occasionally, if the malformation is extremely large, systemic blood flow is compromised, and decreased systemic perfusion may be the dominant finding. In this instance, an erroneous diagnosis of hypoplastic left heart syndrome may be considered initially. If desaturation is prominent, persistent pulmonary hypertension is also a common misdiagnosis.
The physical examination of an infant with a symptomatic arteriovenous malformation is striking. The infant is tachycardic and tachypneic. Oxygen saturation may be normal, but it also may be mildly decreased in the upper extremities because of a right-to-left atrial shunt and further decreased in the lower extremities because of a right-to-left ductal shunt, mimicking pulmonary hypertension of the newborn. If systemic blood flow is
not compromised, the extremities are warm and well perfused, and the pulses are bounding. Even when perfusion is poor and the extremities are cool, the pulses are unusually strong. If appreciated clinically, this is a pathognomonic finding of arteriovenous malformations. The liver is moderately enlarged. The precordium is strikingly hyperactive. The dramatic increase in precordial activity is indicative of the greatly increased blood flow into the right ventricle and of secondary pulmonary arterial hypertension. The first heart sound is normal, the second heart sound is either widely split or single and loud (when pulmonary vascular resistance is elevated), and there may be a nonspecific systolic ejection murmur. Bruits can always be heard over the location of the malformation. Auscultation of head and liver is extremely important in any infant with respiratory distress or decreased systemic perfusion at birth, especially if the pulses and precordial impulse are prominent. If this is included in the routine physical examination in the newborn, the diagnosis of an arteriovenous malformation will not be missed.
Ancillary Tests
• The chest radiograph shows generalized cardiomegaly, including enlargement of the superior vena caval shadow in patients with a vein of Galen malformation.
• The electrocardiogram shows right ventricular hypertrophy and often biventricular hypertrophy even at birth. Enlargement of one or both atria may also be apparent.
• The echocardiogram shows generalized chamber enlargement. The right atrium and right ventricle are particularly large, and the right ventricle appears to be hypercontractile. Dilation of the superior vena cava or inferior vena cava should be apparent, depending on the location of the malformation. The intracardiac anatomy should be defined, and the specific presence of a sinus venosus atrial septal defect should be sought in infants with a vein of Galen malformation. A thorough Doppler evaluation is extremely important, as this can indirectly locate the site of the arteriovenous malformation. The ascending aortic flow signal shows exaggeration of the forward flow in all instances, but retrograde diastolic flow in the aorta will occur distal to the origin of the vessels feeding the malformation. Thus, the entire aorta and head and neck vessels should be interrogated. Rapid and accurate diagnosis is essential because these infants are often quite ill and require prompt intervention.
Therapeutic Considerations
Infants with a large arteriovenous malformation generally require stabilization with positive pressure ventilation and supportive measures to maintain effective systemic circulation. Once the infant has been stabilized, interventional catheterization should be performed promptly. The arteriovenous malformation can often be occluded either partially or completed using coils or other devices and materials. Even partial occlusion may be very helpful in reducing the magnitude of the shunt, thereby minimizing symptoms and allowing the infant to grow normally. Unfortunately, many infants with vein of Galen aneurysm malformations have severe neurologic injury before birth, or it may occur as a result of the intervention, which usually requires large numbers of coils and other methods to fully occlude the abnormal vasculature. This may further impair blood flow to normal brain tissue as well. Complete neurologic evaluation with magnetic resonance imaging is performed before intervention, and in the presence of severe injury, palliative care is often recommended.
■ DEFECTS WITH BIDIRECTIONAL SHUNTS AND EXCESSIVE PULMONARY BLOOD FLOW
This category includes congenital cardiovascular malformations in which the dominant pathophysiologic process is excessive pulmonary blood flow, although the presence of an associated right-to-left shunt causes varying degrees of systemic arterial desaturation. Some of defects with bidirectional shunts cause symptoms of decreased systemic perfusion (total anomalous pulmonary venous connection with obstruction) or cyanosis (double-inlet left ventricle with subvalvar pulmonary stenosis), but only those conditions in which excessive pulmonary blood flow is the dominant pathophysiological process are considered in this chapter.
Total Anomalous Pulmonary Venous Connection Without Obstruction
Anatomic and Physiologic Considerations
The most proximal extracardiac connection that allows for mixing of systemic and pulmonary venous blood is the abnormal connection of the pulmonary veins to either the systemic veins, the coronary sinus, or the right atrium directly. During normal development, the pulmonary veins from the five lobes of the lung approach the midline and coalesce, forming a single pulmonary venous confluence. This confluence then merges into the posterior left side of the primitive atrium, forming a large communication. The mature left atrium is composed of the pulmonary venous confluence and the left half of the primitive atrium.
When the pulmonary venous confluence does not connect normally into the atrium, it coalesces with other venous structures. The most common connection is to the common cardinal system, usually on the left. When this occurs, the confluence joins behind the left atrium and usually ascends as a left vertical vein anterior to the left pulmonary artery, left mainstem bronchus, and aortic arch to join the left innominate vein and then the superior vena cava (Figure 7-9). Occasionally, the vertical vein passes between the left pulmonary artery and the left mainstem bronchus, causing severe obstruction. Less commonly, the ascending trunk ascends the right side of the mediastinum and enters the back of the superior vena cava or the azygous vein. This is more commonly associated with mixed anomalous pulmonary venous drainage and other complex anomalies, such as right atrial isomerism.
The next most common connection is infradiaphragmatic, in which the pulmonary venous confluence descends below the diaphragm, anterior to the esophagus, and joins the umbilicovitelline venous system. This form of anomalous pulmonary venous connection is almost always obstructed at birth because the pulmonary venous return must enter the relatively small portal system as the ductus venosus closes. Since the pathophysiology and clinical presentation of obstructed pulmonary venous return differ significantly from the defects that cause excessive pulmonary blood flow, infradiaphragmatic anomalous pulmonary venous connection is discussed in Chapter 8.
The third most common site of connection is directly to the coronary sinus. In this case, the pulmonary venous confluence lies entirely within the pericardium and connects to the middle portion of the coronary sinus in the atrioventricular groove. This connection is rarely obstructed.
Finally, the pulmonary veins may connect directly to the right atrium. This usually is not a single connection, but there is mixed drainage with the right-sided pulmonary veins connecting to the right atrium and the left-sided pulmonary veins connecting to the left atrium. This form of anomalous pulmonary venous connection is commonly associated with heterotaxy (left atrial isomerism; Chapter 6).
FIGURE 7-9. Total anomalous pulmonary venous connection above the diaphragm. In this defect, the fully saturated pulmonary venous blood returns via the left innominate vein to the superior vena cava and, along with systemic venous return from the upper body, preferentially crosses the tricuspid valve to the right ventricle and main pulmonary artery. The less saturated systemic venous blood from the inferior vena cava passes preferentially across the foramen ovale to the left atrium and then into the left ventricle and ascending aorta. Therefore, pulmonary arterial oxygen saturation is higher than ascending aortic oxygen saturation. If there is a patent ductus arteriosus, a small right-to-left shunt causes descending aortic oxygen saturation to be higher than that in the ascending aorta. Contrast this diagram with the idealized situation depicted in Figure 7-2, where complete mixing is assumed to occur in the right atrium. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
The connections of the pulmonary veins may also be mixed. Most frequently, the left upper pulmonary vein connects superiorly via a vertical vein to the left innominate vein, while the left lower and right pulmonary veins connect inferiorly below the diaphragm or to the right superior vena cava.
Clinical Presentation
The newborn with total anomalous pulmonary venous connection without obstruction is not symptomatic at birth, although transient cyanosis may be present. The presence of mild arterial desaturation at birth is now much more frequently appreciated because of the use of screening pulse oximetry. Most newborns with unobstructed total anomalous pulmonary venous connection have supradiaphragmatic drainage of the veins (either via a left vertical vein or, less commonly, via the coronary sinus). In both of these situations, the fully saturated pulmonary venous blood follows the path of superior vena caval flow, preferentially crossing the tricuspid valve into the right ventricle (Figure 7-9). The less saturated inferior vena caval blood preferentially crosses the foramen ovale to the left ventricle and ascending aorta. If the ductus arteriosus remains patent, a small right-to-left ductal shunt usually occurs because of the increased pulmonary blood flow. The right-to-left shunt causes the arterial oxygen saturation in the lower extremities to be higher than that in the upper extremities. The only other condition in which upper extremity saturation is less than that in the lower extremity is d-transposition of the great arteries. In d-transposition of the great arteries, however, upper extremity saturation is much lower than in total anomalous pulmonary venous connection. Thus, the finding of higher oxygen saturation by pulse oximetry in the lower extremity of a patient with mild cyanosis is pathognomonic of supradiaphragmatic total anomalous pulmonary venous connection.
If cyanosis is not present at birth, the infant usually feeds well and often is discharged from the hospital without the defect being recognized. As pulmonary vascular resistance decreases, the right ventricle remodels and becomes more compliant. This increases pulmonary blood flow and systemic arterial saturation. Over time, symptoms of tachypnea and failure to thrive often develop. The infant may be unnecessarily evaluated for pulmonary or gastrointestinal disease if the cardiac disease is not recognized. Alternatively, the diagnosis may be made in an infant with a respiratory infection who has unexpected cyanosis or cardiomegaly seen on the chest radiograph.
On physical examination, the infant often appears thin and mildly tachypneic. Pulse oximetry usually shows oxygen saturations around 85% to 92%. Pulses and perfusion are generally normal, and the liver is mildly enlarged. The lungs are clear to auscultation although retractions are often present. The precordium is moderately hyperactive with a parasternal impulse. The first heart sound is normal, and the second heart sound is usually widely split with mild accentuation of the pulmonic component. An audible S3 may be present. A murmur may be absent, which may contribute to the delay in diagnosis, or there may be a soft systolic ejection murmur heard best at the left upper sternal border, which reflects the markedly increased pulmonary blood flow.
Ancillary Tests
• The chest radiograph shows a normal-size heart with increased vascularity in the newborn, but if the diagnosis is delayed, cardiomegaly is present. A large vertical vein in the left upper mediastinum and enlargement of the superior vena cava in the right give the typical “snowman” appearance in cases of anomalous connection to the left innominate vein (Figure 7-10).
• Electrocardiography shows right ventricular hypertrophy with prominent R waves and upright T waves in the right precordium. Right atrial enlargement is suggested by tall-peaked P waves in lead II.
• Echocardiography and color Doppler studies make the diagnosis of anomalous pulmonary venous connection much easier and more reliable. Because there is often a large pulmonary venous confluence behind the left atrium and the course of the pulmonary veins is normal, recognizing that the veins do not connect with the left atrium can be difficult. However, color Doppler can clearly show whether the flow of blood from the pulmonary veins actually enters the left atrium or whether it travels anomalously (superiorly in supradiaphragmatic connection or inferiorly if the confluent vein travels below the diaphragm to the portal system). When an anomalous connection is observed, it is important to assess the course of each pulmonary vein to ensure that the connection is not mixed and to exclude associated heart disease. Cardiac catheterization can usually be avoided if all of the veins are defined. Magnetic resonance imaging can be extremely helpful in defining the extracardiac venous connections. The left ventricle often appears hypoplastic because right ventricular volume is so much greater than left. However, the left ventricle is always of adequate size, and coarctation of the aorta is not associated with this defect.
Therapeutic Considerations
Anomalous pulmonary venous connection is treated surgically. The specific approach depends on the details of the anatomy and course of the anomalous connections. In most cases, the pulmonary confluence behind the left atrium is anastomosed to the left atrium to allow pulmonary venous return to enter the left atrium. The vertical vein is usually ligated.
FIGURE 7-10. Chest radiograph in an infant with total anomalous pulmonary venous connection to the superior vena cava. A large vertical vein in the left upper mediastinum and enlargement of the superior vena in the right give the typical “snowman” appearance.
Single-Ventricle Physiology Without Outflow Obstruction
Anatomic and Physiologic Considerations
A large number of congenital cardiovascular malformations are associated with complete mixing of systemic and pulmonary venous blood in a functionally single ventricular chamber. Of the patients with single-ventricle physiology, only about one-third have unobstructed pulmonary and aortic outflow tracts. Most instead have pulmonary outflow obstruction and consequently present with cyanosis as the predominant manifestation (Chapter 6). A smaller number have subaortic and aortic arch obstruction and consequently present with decreased systemic perfusion as the predominant clinical problem (Chapter 8). In the remaining subset of infants with a single ventricle and unobstructed outflow, blood flows preferentially into the pulmonary artery, and the predominant clinical manifestations are the result of excessive pulmonary blood flow.
The anatomy of these hearts is extremely variable. These defects are best described by their atrioventricular valve morphology, atrial-ventricular and ventricular- arterial connections, ventricular morphology, and associated defects.
Two normal atrioventricular valves, atresia or straddling of one or the other atrioventricular valve, or a common atrioventricular valve may be present. The atrial- ventricular connections may be concordant (ie, right atrium connects to the right ventricle, and left atrium connects to the right ventricle), discordant (right atrium connects to the left ventricle, and left atrium connects to the right ventricle), or double inlet (to the left ventricle). The ventricular-arterial connections may be concordant (right ventricle connects to the pulmonary artery, and left ventricle connects to the aorta), discordant (right ventricle connects to the aorta, and left ventricle connects to the pulmonary artery), or double outlet (to the right ventricle) (Figure 7-11). Certain connections tend to track together. For example, the most common form of single-ventricle physiology without outlet obstruction is l-malposition of the great arteries (ventricular-arterial discordance). When the great arteries are l-malposed and the physiology is that of a single ventricle, there are usually two normal atrioventricular valves, double-inlet left ventricle, and a subaortic outflow chamber of right ventricular morphology. In left atrial isomerism (sometimes called polysplenia; Chapter 6), an atrioventricular septal defect with a ventricle of uncertain morphology is often present, and there are many associated findings, such as interrupted inferior vena cava with azygous continuation, bilateral superior vena cavae, abnormal pulmonary venous connection, a large atrial septal defect or common atrium, and bilateral left pulmonary arterial morphology.
Clinical Presentation
Independent of the precise anatomy, the clinical findings in infants with a single ventricle and unobstructed pulmonary blood flow are similar to those in infants with excessive pulmonary blood flow and bidirectional shunting caused by other types of structural defects. Growth is impaired, and oxygen saturation is modestly decreased. The liver and stomach positions should be evaluated for evidence of situs inversus or situs ambiguous, which can lead to specific cardiac diagnoses and noncardiac abnormalities. For example, a midline liver suggests the diagnosis of left atrial isomerism, which is associated with biliary atresia and intestinal malrotation. The precordium is active and can be mid-sternal or located on either side of the sternum. The second heart sound is rarely heard to split because of the abnormal position of the pulmonary valve and the elevated pulmonary arterial diastolic pressures. Murmurs are often present, but their location, frequency, and characteristics depend on the specific anatomy, which can be quite variable.
FIGURE 7-11. Atrial-ventricular and ventricular-arterial connections. A. The normal heart has concordant atrial-ventricular and ventricular-arterial connections. B. Atrial-ventricular concordance and ventricular-arterial discordance is seen in d-transposition of the great arteries. C. Atrial-ventricular and ventricular-arterial discordance is seen in l-transposition of the great arteries. D. Atrial-ventricular discordance and ventricular-arterial concordance is found in the rare condition of isolated ventricular inversion. In conditions B and D, systemic venous blood returns directly to the aorta so that the patient is cyanotic.
Ancillary Tests
• The chest radiograph is very variable but can be used to determine the size of the heart, its location within the thorax, the direction that the apex is pointing, the presence of symmetrical lungs, and the amount of vascularity.
• The electrocardiogram is also variable, depending on the specific anatomic defects. The atrial forces should be evaluated to determine the axis of atrial conduction, paying particular attention to the presence of an inferior pacemaker with a superior axis (which occurs in left atrial isomerism). Atrioventricular conduction block should be carefully considered because it occurs commonly in left atrial isomerism and l-malposition of the aorta.
• The echocardiogram is extremely useful for defining cardiac anatomy, function of the atrioventricular and semilunar valves, pulmonary arterial blood flow, and associated arterial and venous anomalies. In addition to echocardiography, an abdominal ultrasound should be performed because of the nearly universal finding of malrotation in patients with situs abnormalities. Determining the anatomy of the gastrointestinal tract may help in the diagnosis of intestinal obstruction later. Liver function should also be assessed because of the association of biliary atresia if left atrial isomerism is considered in the differential.
Therapeutic Considerations
Regardless of the specific anatomic details, the general approach to these infants is similar. The ultimate goal is to separate the pulmonary and systemic circulations by use of a bidirectional Glenn shunt and modified Fontan operation (Chapter 6). In the neonate and young infant, aggressive medical and nutritional therapy is indicated to minimize symptoms and promote normal growth. In cases of severe refractory heart failure, early surgical intervention to reduce the amount of pulmonary blood flow becomes necessary. This can be accomplished by banding the main pulmonary artery (see following text). Alternatively, the pulmonary artery is surgically disconnected from the ventricle, and a systemic-to-pulmonary artery shunt is placed. Patients with malrotation are usually referred for a prophylactic surgical procedure to prevent intestinal obstruction in the future.
Truncus Arteriosus
Anatomic and Physiologic Considerations
One of the more common defects with bidirectional shunting and excessive pulmonary blood flow is trun- cus arteriosus. The primary developmental defect in this defect is failure of septation of the aorto-pulmonary septum and the truncus arteriosus (Chapter 1). The failure of aorto-pulmonary septation results in a single arterial trunk from which arise the ascending aorta, the pulmonary arteries, and the coronary arteries (Figure 7-12). Failure of septation of the truncus arteriosus results in a single semilunar valve as the outlet for both ventricles. The truncal valve may have from one to six valve leaflets, though most commonly it is a tricuspid valve. The valve is frequently dysplastic and may be associated with significant insufficiency or, less commonly, stenosis.
Abnormal migration of ectomesenchymal cells derived from the cardiac neural crest has been implicated in the pathogenesis of this defect. This field defect is also associated with abnormalities in parathyroid and thymic function seen in microdeletion 22q11 (DiGeorge) syndrome. This syndrome occurs in approximately one-third of infants with truncus arteriosus and is more common when the aortic arch is right sided. The ductus arteriosus is absent except when there is an interrupted aortic arch.
Truncus arteriosus is classified into various categories depending on the origins of the branch pulmonary arteries and the presence of an interrupted aortic arch. Most commonly, the two pulmonary arteries arise either as a single trunk (type I) or with a fine raphe separating them (type II) from the posterior and leftward side of the trunk. In this configuration, truncus arteriosus is not a complete mixing defect. Because the left ventricle ejects blood anteriorly and to the right and the right ventricle ejects blood posteriorly and to the left, the left ventricle will preferentially eject into ascending aorta and the right ventricle into the branch pulmonary arteries (Figure 7-12). Often, there is a separation in saturation of about 5% to 8% between the two vascular beds, with the ascending aortic saturation being higher. This is the reason that, when systemic oxygen saturation measured by pulse oximetry is 94% to 95%, pulmonary blood flow is not actually 10 times that of systemic blood flow (as would be predicted if complete mixing were assumed). Usually, the systemic oxygen saturation is around 88% to 92%, and pulmonary blood flow is about three to four times that of systemic blood flow. Clearly, this physiology is not associated with either visible cyanosis or metabolically significant systemic desaturation. Instead, the infant will have symptoms of excessive pulmonary blood flow.
FIGURE 7-12. Truncus arteriosus. The right ventricle ejects the desaturated systemic venous blood posteriorly and to the left, whereas the left ventricle ejects the well-oxygenated pulmonary venous blood anteriorly and to the right. Because of these flow patterns, blood in the ascending aorta is somewhat more saturated than blood in the pulmonary arteries. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
Clinical Presentation
On physical examination, cyanosis may be observed only in the first few hours or first day of life, while pulmonary vascular resistance is still relatively high. The rapid fall in pulmonary vascular resistance results in arterial oxygen saturations in the range of 85% or higher very soon after birth because shunting occurs during both systole and diastole. This feature makes cyanosis difficult to appreciate after the first few hours of life. Over time, the infant becomes more tachypneic with significant intercostal and subcostal retractions. Failure to thrive is almost universal, except when there is the rare occurrence of stenosis of the pulmonary arterial ostium. Tachycardia and diaphoresis are prominent. The facies of microdeletion 22q11 syndrome may be present, including a sloping forehead, hypertelorism, micrognathia, low-set and posteriorly rotated ears, and a small mouth. The pulses are bounding in all extremities except when the aortic arch is interrupted, in which case the infant presents with diminished systemic perfusion if the ductus arteriosus begins to close. However, it seems that ductal closure in infants with truncus arteriosus and interrupted aortic arch occurs less commonly than in other infants with heart disease. There is moderate hepatomegaly. The precordium is hyperactive, though no thrill is present unless there is truncal valve stenosis, which may cause a suprasternal notch thrill. The first heart sound is normal, and the second heart sound is single and loud because of the single semilunar valve. An important and extremely frequent finding is a systolic ejection click arising from the dysplastic truncal valve. There is usually a harsh systolic ejection murmur of mid- to high frequencies around the mid-sternum. The systolic murmur radiates to the lungs and to the carotid arteries. An early diastolic murmur of truncal valve insufficiency should be carefully sought. Often, an apical mid-diastolic murmur is present, reflecting the very large pulmonary blood flow and increased inflow across the mitral valve.
Ancillary Tests
• The chest radiograph shows generalized cardiomegaly with increased pulmonary vascular markings. A strong clue to the diagnosis is the presence of an abnormal structure in the left upper mediastinum, which represents the elevated takeoff of the left pulmonary artery (Figure 7-13).
• The electrocardiogram shows right and usually biventricular hypertrophy within the first weeks of life, and left atrial enlargement may also be evident.
• The echocardiogram is diagnostic, showing the common trunk with the takeoff of the great arteries and the coronary arteries as it ascends. It is important to evaluate the origin of both branch pulmonary arteries, the function of the truncal valve, associated muscular ventricular septal defects, the orientation of the aortic arch, and the presence or absence of aortic arch interruption.
FIGURE 7-13. Chest radiograph in an infant with truncus arteriosus. The important findings are a left ventricle forming apex, a right aortic arch, and the high takeoff of the left pulmonary artery from the common trunk.
Therapeutic Considerations
Truncus arteriosus requires surgical repair, often in the neonatal period. Heart failure and failure to thrive can be severe, and unless there are compelling reasons that preclude surgical intervention, repair in the neonatal period is recommended. Several different surgical techniques are utilized with the common goal of closing the ventricular septal defect in such a fashion that the left ventricle ejects across the truncal valve into the ascending aorta. The pulmonary arteries are disconnected from the common trunk and connected to the right ventricle using some type of conduit. Repair of truncus arteriosus in infancy requires additional surgical procedures in the future to replace the right ventricular to pulmonary artery connection as the child grows.
■ PULMONARY ARTERY BAND
If a patient has high pulmonary blood flow for a long period of time, congestive heart failure, failure to thrive, pulmonary hypertension, and pulmonary vascular disease are all possible complications. Generally, patients with defects such as a large ventricular septal defect or atrioventricular septal defect undergo open-heart repair before 6 to 12 months of age to prevent such complications. Some patients are not candidates for open-heart repair because, for example, they have defects that have functional “single-ventricle” physiology, as described above. A pulmonary artery band (Figure 7-14) often serves as reasonable palliation in these patients. Banding the pulmonary artery involves placing a ligature around the main pulmonary artery and tightening it so that an artificial obstruction is created. The degree of tightening requires critical judgment on the part of the surgeon; too little constriction will cause the patient to have too much pulmonary blood flow and remain at risk for complications, such as heart failure and pulmonary vascular disease, and too much constriction will result in the patient becoming too cyanotic either immediately or after a relatively small amount of growth. The band should be placed at the middle portion of the main pulmonary artery; it should not be too close to the pulmonary valve to avoid injury to the valve, which may lead to insufficiency, or too close to the bifurcation of the pulmonary arteries, which might lead to branch pulmonary artery distortion and possibly unbalanced flow to the two lungs. Bands may migrate after placement in either direction, causing either valve injury or bronchi distortion.
FIGURE 7-14. Pulmonary artery band. Ideally, the band should be placed in the middle portion of the main pulmonary artery to avoid distortion of the pulmonary valve or origins of the right and left pulmonary arteries. Abbreviations: Ao, aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; RA, right atrium; RV, right ventricle.
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 29-31, 35, 44, 52, 53.
Hoffman JIE. The Natural and Unnatural History of Congenital Heart Disease. Oxford, England: Wiley-Blackwell; 2009.
Park MK. The Pediatric Cardiology Handbook. 4th ed. Philadelphia, PA: Mosby Elsevier; 2010.
Rudolph AM. Congenital Diseases of the Heart: Clinical- Physiological Considerations. Chichester, England: Wiley- Blackwell; 2009:chaps 7, 9, 13, 19.
Left-to-Right Shunts
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Bidirectional Shunts With Dominant Left-to-Right Shunt
Alton GY, Robertson CM, Sauve R, et al. Early childhood health, growth, and neurodevelopmental outcomes after complete repair of total anomalous pulmonary venous connection at 6 weeks or younger. J Thorac Cardiovasc Surg. 2007;133:905-911.
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Karamlou T, Gurofsky R, Al Sukhni E, et al. Factors associated with mortality and reoperation in 377 children with total anomalous pulmonary venous connection. Circulation. 2007;115:1591-1598.
McElhinney DB, Driscoll DA, Emanuel BS, et al. Chromosome 22q11 deletion in patients with truncus arteriosus. Pediatr Cardiol. 2003;24:569-573.
Pulmonary Arterial Banding
Alsoufi B, Manlhiot C, Ehrlich A, et al. Results of palliation with an initial pulmonary artery band in patients with single ventricle associated with unrestricted pulmonary blood flow. J Thorac Cardiovasc Surg. 2015;149:213-220.