Approach to the Infant With Inadequate Systemic Perfusion

Neonatal Cardiology, 3rd Ed. Michael Artman

Chapter 8. Approach to the Infant With Inadequate Systemic Perfusion

■ INTRODUCTION

■ PATHOPHYSIOLOGY OF INADEQUATE SYSTEMIC PERFUSION

Fetal Physiology and the Transition at Birth

■ LEFT HEART OBSTRUCTION

Total Anomalous Pulmonary Venous Connection With Obstruction

Cor Triatriatum

Mitral Stenosis

Hypoplastic Left Heart Syndrome Valvar Aortic Stenosis Interruption of the Aortic Arch Coarctation of the Aorta

■ SUGGESTED READINGS

■ INTRODUCTION

Inadequate systemic perfusion is the second most common manifestation of symptomatic heart disease in newborn infants. Affected infants present with moderate to severe respiratory distress in addition to signs of decreased systemic perfusion. Respiratory distress is caused by increased pulmonary venous pressure causing pulmonary edema. Pulmonary venous pressures are increased because (1) there is obstruction to the egress of blood from the lungs or from the left atrium into the left ventricle or (2) the left ventricle cannot adequately eject blood. In some infants, the decrease in systemic perfusion is profound, with decreased to absent peripheral pulses, cool extremities, hypotension, and severe metabolic acidosis. In these cases, the compromise of systemic blood flow is life threatening and requires urgent diagnosis and therapy. In other infants, respiratory distress is the most impressive finding, and the signs of decreased systemic perfusion are subtle, often leading to the erroneous conclusion that the infant has primary pulmonary disease rather than heart disease. This is particularly true when the infant does not have a heart murmur, which may occur in this group of cardiac defects. Signs of decreased systemic perfusion, which may be indicated solely by mildly decreased pulses or by a mild metabolic acidosis, should be carefully sought and considered in all infants with significant respiratory distress.

The two hemodynamic categories of cardiovascular pathophysiology that cause decreased systemic perfusion are left heart obstruction and cardiomyopathy. This chapter will review the various anatomic defects that cause left heart obstruction. Cardiomyopathies in newborn infants are reviewed in Chapter 9.

■ PATHOPHYSIOLOGY OF INADEQUATE SYSTEMIC PERFUSION

The primary pathophysiologic abnormality in the infant with inadequate systemic perfusion is the inability of the heart to supply an adequate amount of oxygen to the tissues to meet metabolic needs. In this context, the onset is more acute and severe as compared with the chronic heart failure syndrome discussed in Chapter 11. Furthermore, in contrast to cyanotic infants (Chapter 6), oxygen saturation is usually normal or only mildly decreased in infants with decreased systemic perfusion. Instead, the overriding problem is inadequate systemic blood flow.

Fetal Physiology and the Transition at Birth

In the normal fetus, different ventricles perfuse the upper and lower portions of the body. The right ventricle supplies the lower body, and the left ventricle supplies the upper body. During fetal life, obstruction to one ventricle, or a myopathic process isolated to that ventricle, does not lead to decreased systemic perfusion. Inflow can be diverted to the healthy unobstructed ventricle via the foramen ovale, and a portion of the outflow of the healthy ventricle can be diverted to the other vascular bed via the ductus arteriosus (Chapter 3, Figure 3-5). Left-sided obstruction causes decompensation after birth because the postnatal changes in the circulation prevent the right ventricle from performing the work of the left ventricle. At birth, pulmonary blood flow increases greatly, causing the flap of the foramen ovale to close the atrial communication. In newborn infants in whom blood flow into or out of the left ventricle is critically obstructed, closure of the foramen ovale causes decreased systemic perfusion almost immediately after birth. Blood flow may cross the foramen ovale in a left- to-right direction, but this occurs at the cost of increased left atrial pressures. Thus, an early and important finding in these infants is pulmonary edema, resulting in severe respiratory distress.

Some infants have either an open incompetent foramen ovale or a more distal obstruction (eg, coarctation of the aorta) that is not dependent on decompression through the foramen ovale. Adequate systemic perfusion in these infants depends on patency of the ductus arteriosus. In the infant with hypoplastic left heart syndrome or interruption of the aortic arch, adequate systemic blood flow depends on a widely patent ductus arteriosus. Thus, these infants typically develop symptoms within the first 72 hours of life as the ductus arteriosus begins to constrict. In contrast, infants with coarctation of the aorta do not require full patency of the ductus arteriosus but merely a large ductal ampulla to maintain flow around the coarctation site into the descending aorta. The ampulla, which is located at the aortic end of the ductus arteriosus, provides a pathway for blood to flow from the aortic arch past the site of coarctation to the descending aorta (Figure 8-1). The ductus arteriosus constricts initially at the pulmonary end, and only days later does the constriction progress to the aortic end. Thus, aortic obstruction and associated symptoms may be delayed for several days or weeks after birth in infants with significant coarctation of the aorta.

FIGURE 8-1. Coarctation of the aorta. Even when the ductus is fully closed in its middle portion, the presence of an aortic ampulla allows for blood flow to bypass the coarctation site without significant obstruction to the descending aorta.

■ LEFT HEART OBSTRUCTION

Left heart obstruction may occur either at the inflow of blood to the left atrium or ventricle or at the outflow of blood from the left ventricle. The defects can be considered according to the anatomical site of obstruction, starting at the pulmonary veins and progressing through the left heart to the ascending and descending aorta (Table 8-1).

Total Anomalous Pulmonary Venous Connection With Obstruction

Anatomic and Physiologic Considerations

The most proximal obstruction to filling of the left heart occurs at the level of the pulmonary veins. The embryonic pulmonary venous confluence is not part of the true left atrium but is a coalescence of the pulmonary veins from the five lobes of the lungs that eventually connects to the left atrium. In total anomalous pulmonary venous connection, the confluence does not connect to the left atrium; instead, it connects to various venous structures above or below the diaphragm. Pulmonary veins draining above the diaphragm usually have only modest pressure gradients associated with high flow through the venous channels. As discussed in Chapter 7, infants with supradiaphragmatic total anomalous pulmonary venous connection usually present with tachypnea secondary to high pulmonary blood flow rather than decreased systemic perfusion. An uncommon exception occurs when the superior course of a left vertical vein passes between the left pulmonary artery and bronchus rather than in front of both. This is termed a hemodynamic vise. As the left pulmonary artery and pulmonary veins fill with blood after birth, the vertical vein becomes compressed, and the predominant signs are due to decreased systemic perfusion.

TABLE 8-1. Left-Sided Obstructive Defects
Anatomic level	Structural defect
Pulmonary veins	Total anomalous pulmonary venous connection with obstruction
Left atrium	Cor triatriatum Supravalvar mitral web/ring
Mitral valve	Atresia Stenosis (± parachute mitral valve)
Left ventricle	Hypoplastic left heart syndrome Subaortic stenosis
Aortic valve	Atresia Stenosis
Aorta	Supravalvar aortic stenosis Aortic arch hypoplasia Aortic arch interruption Coarctation of the aorta

The most common anomalous pulmonary venous connection that is associated with postnatal pulmonary venous obstruction occurs when the pulmonary venous confluence coalesces below the diaphragm with the umbilicovitelline system. In this situation, the pulmonary venous confluence descends anterior to the esophagus and connects near the liver to the portal system or the ductus venosus (Figure 8-2). Because the ductus venosus is large in utero and pulmonary blood flow is small, the connection is unobstructed during fetal life. Immediately after birth, pulmonary blood flow increases greatly, and the loss of placental blood flow is associated with constriction of the ductus venosus. These changes at birth result in increased flow through the anomalous venous channel, which is inadequate to provide unimpeded flow. The result is obstruction to egress of blood from the lungs, marked increase in pulmonary venous pressure, and pulmonary edema.

Determining the location of the abnormal connection in a newborn infant with total anomalous pulmonary venous connection with obstruction may be possible at the bedside if the ductus arteriosus is patent. When pulmonary venous outflow is obstructed, pulmonary vascular resistance is high, and right-to-left shunting occurs across the ductus arteriosus. If the veins drain superiorly, the pulmonary venous return preferentially descends with the superior vena caval flow toward the tricuspid valve, then into the right ventricle, main pulmonary artery, ductus arteriosus, and descending aorta. Consequently, oxygen saturation in the lower portion of the body is higher than that in the upper body. Conversely, if the veins drain below the diaphragm, pulmonary venous blood preferentially crosses the foramen ovale to the left atrium and ventricle and ascending aorta (Figure 8-2). In this situation, oxygen saturation in the lower portion of the body is lower than that in the upper body.

Clinical Presentation

The clinical presentation of the infant with obstructed total anomalous venous connection is dramatic and occurs shortly after birth. Moderate to severe respiratory distress with tachypnea, intercostal and subcostal retractions, nasal flaring, and grunting develop soon after birth. Oxygen saturation measured by pulse oximetry is usually modestly decreased, often in the mid-80s, but it may be much lower if obstruction is severe. As discussed above, a small difference in oxygen saturation may be present between the upper and lower extremities if the ductus arteriosus is patent. The pulses are often mildly to moderately decreased in all extremities, and perfusion may be similarly decreased. The blood pressure may show a narrow pulse pressure. The precordium is hyperactive with a prominent parasternal impulse because the right ventricle is ejecting much more blood than normal and is doing so at suprasystemic pressures. The first heart sound is normal, and splitting of the second heart sound often is easy to hear because of the markedly increased pulmonary blood flow in patients who do not have obstructed pulmonary venous return. A split second heart sound in the newborn infant with decreased systemic oxygen saturation is very unusual and strongly supports the diagnosis of total anomalous pulmonary venous connection. A nonspecific murmur associated with increased flow across the right ventricular outflow tract may be present, although this may not be present when severe pulmonary venous obstruction is present.

This presentation is easily confused with persistent pulmonary hypertension of the newborn infant, another life-threatening condition with a similar early course of severe decompensation. Moreover, pulmonary arterial pressure is often suprasystemic in infants with total anomalous pulmonary venous connection with obstruction, which further complicates differentiating between these two conditions.

It is critically important to differentiate the two as soon as possible because emergency surgery can be lifesaving in the infant with total anomalous pulmonary venous connection. To do so, it is valuable to consider the perinatal period. The prenatal course and delivery are usually benign in the infant with obstructed total anomalous pulmonary venous connection. In contrast, the infant with pulmonary hypertension frequently has a history of perinatal complications such as premature rupture of membranes, meconium in the amniotic fluid if not frank aspiration, low Apgar score, in utero growth retardation, or other findings consistent with perinatal distress.

FIGURE 8-2. Total anomalous pulmonary venous connection below the diaphragm. Fully saturated pulmonary venous blood descends in the anomalous venous confluence below the diaphragm and inserts into to the portal venous system. At birth, pulmonary blood flow increases, and the ductus venosus constricts, together increasing pulmonary venous pressures and causing pulmonary edema. As described in the text, there is preferential streaming within the atria so that if there is a patent ductus arteriosus (as shown in this diagram), a small right-to-left shunt causes descending aortic saturation to be lower than that in the ascending aorta. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Despite the potential differences in the perinatal course, a high index of suspicion is critical if the correct diagnosis is to be made quickly. Because of the difficulty in differentiating the two conditions, every infant who is thought to have persistent pulmonary hypertension of the newborn should undergo echocardiography urgently to evaluate the possibility that the pulmonary hypertension is caused by total anomalous pulmonary venous connection with obstruction.

Ancillary Tests

• The chest radiograph in infants with anomalous pulmonary venous connection shows a small to normalsize heart and diffusely increased vascularity, with alveolar and interstitial edema (Figure 8-3). The markings are less coarse than those of meconium aspiration seen in the infant with persistent pulmonary hypertension, but this is a subtle difference.

• The electrocardiogram may be helpful in differentiating total anomalous pulmonary venous connection from pulmonary hypertension of the newborn. A “qR” pattern in the right precordial leads, which reflects severe right ventricular hypertrophy because of the markedly increased pulmonary arterial pressures, is frequently present in infants with anomalous pulmonary venous connection (Figure 8-4). Although persistent pulmonary hypertension of the newborn also may cause right ventricular hypertrophy, it is usually manifested as failure of inversion of the T waves in the first 2 weeks of life and not as a “qR” pattern in the right precordium.

• Echocardiography is diagnostic of total anomalous pulmonary venous connection and should be performed on all infants suspected of having pulmonary hypertension of the newborn. Furthermore, echocardiography is indicated for all infants being considered for extracorporeal membrane oxygenation and in whom a definitive diagnosis has not been made. However, making the correct diagnosis and defining the precise pulmonary venous anatomy requires a skilled and experienced echocardiographer. Exclusive right-to-left shunting across the foramen ovale is always found in patients with anomalous pulmonary venous connection. Color Doppler echocardiography has facilitated definition of venous anatomy (Figure 8-5). Color flow patterns can demonstrate the location of the obstruction, and pulsed wave Doppler can estimate its severity.

FIGURE 8-3. TAPVC chest radiograph. Note that the cardiac silhouette is normal, without cardiomegaly, yet there is diffuse edema throughout all lung fields, The patient was intubated very soon after birth because of severe respiratory distress.

Therapeutic Considerations

Endotracheal intubation, positive pressure ventilation, and stabilization of the metabolic status of infants with obstructed anomalous pulmonary venous connection should be instituted immediately. Positive end-expiratory pressures may decrease alveolar edema and dramatically improve the ventilatory and cardiovascular status of the infant acutely. Prostaglandin E1 should be administered to infants in whom obstructed total anomalous venous connection is suspected, without waiting for echocardiography to be performed. Prostaglandin E1 may be helpful in dilating the ductus venosus and may be lifesaving in other causes of left-sided obstruction, so administration of this medication should be initiated even before a definitive diagnosis is obtained. Once the diagnosis is made, prostaglandin E₁ may be discontinued if no longer indicated. After stabilization and definitive diagnosis, the infant with total anomalous pulmonary venous connection with obstruction should be taken urgently to the operating room for repair.

Cor Triatriatum

Anatomic and Physiologic Considerations

Pulmonary venous return to the heart may be obstructed at the entrance to the left atrium. Congenital stenosis of one or more pulmonary veins occurs rarely. This is usually a progressive disease that presents later than the newborn period. Results of interventional and surgical approaches are generally disappointing. Recently, acquired pulmonary vein stenosis involving one or more pulmonary veins has been noted in premature infants with bronchopulmonary dysplasia, which also appears to have a poor prognosis.

FIGURE 8-4. TAPVC electrocardiogram. The electrocardiogram on the first day of life shows severe right ventricular hypertrophy, with a qR pattern in V3R and pure R waves with inverted T waves in V1, decreased left-sided forces, and no evidence of atrial hypertrophy.

FIGURE 8-5. Echocardiographic still frame obtained from an infant with total anomalous pulmonary venous connection. Color Doppler study shows two large blood vessels, both with flow descending below the diaphragm. The posterior vessel is the descending aorta, and the anterior vessel is the pulmonary venous confluence descending to connect to the portal venous system. Pulsed Doppler waveforms (not shown in this figure) can demonstrate that the posterior vessel has an arterial waveform and that the anterior vessel has a venous waveform.

More commonly, obstruction occurs between the pulmonary venous confluence and the primitive left atrium during formation of the heart. The left atrium is effectively separated into two chambers, and the condition is therefore called cor triatriatum, meaning “heart with three atria.” It is possible that the developmental mechanisms that result in anomalous pulmonary venous connection and cor triatriatum are similar, but in cor triatriatum, the confluence comes in close enough contact with the atrium to create a single chamber but with incomplete coalescence. The pulmonary veins usually enter the accessory chamber that is connected to the left atrium by an opening of variable size (Figure 8-6). Although the anatomy may be variable, the more distal true left atrium usually communicates with the left atrial appendage and the foramen ovale.

Clinical Presentation

The majority of infants with cor triatriatum appear normal at birth and present later in infancy with failure to thrive, recurrent lung infections, or signs of pulmonary hypertension. Occasionally, the obstruction is so mild that presentation is delayed for many years, at which point the most common complaint is decreased exercise capacity.

If pulmonary venous obstruction is severe at birth, the presentation is similar to that of obstructed total anomalous pulmonary venous drainage, except that the infant often has normal or near normal pulse oximetry and the second heart sound is narrowly split. Thus, this condition also can be misdiagnosed as persistent pulmonary hypertension of the newborn.

Ancillary Tests

• The chest radiograph shows diffuse, interstitial edema with a normal-size heart.

• The electrocardiogram is usually normal at birth but over time shows right ventricular hypertrophy.

• Echocardiography shows a membrane within the left atrial chamber. The relationship between the membrane and the left atrial appendage and foramen ovale should be defined as well as the sites of entry of the pulmonary veins. The presence of turbulence in the mid-cavity of the left atrium is diagnostic, and signs of pulmonary hypertension are present. Doppler studies are helpful in defining the degree of obstruction.

Therapeutic Considerations

These patients should be referred for surgical resection of the membrane. The prognosis is excellent, even if prolonged pulmonary hypertension is present.

Mitral Stenosis

Anatomic and Physiologic Considerations

Critical mitral stenosis or mitral atresia usually leads to hypoplastic left heart syndrome, which will be discussed in the following section. However, other abnormalities of mitral inflow may be associated with inadequate systemic perfusion, particularly when associated with other defects. Supravalvar mitral rings or webs can increase left atrial pressure and cause alveolar edema, but these defects usually do not cause enough obstruction in a newborn infant to result in symptoms at birth.

A parachute mitral valve most commonly causes severe inflow obstruction and is associated with complex outflow obstruction as well. The presence of a parachute mitral valve (with or without a supravalvar mitral ring), subvalvar and valvar aortic stenosis, and coarctation of the aorta is called Shone syndrome. The parachute mitral valve consists of a single papillary muscle to which chordae from both leaflets attach (like a parachute), causing the valve to open only partially. Other abnormalities of the mitral valve causing stenosis may occur at the annulus (hypoplasia), at the leaflets (commissural fusion or dysplasia), or at the chordae (shortened or absent chordae causing a mitral arcade).

Clinical Presentation

The clinical presentation of the infant with Shone syndrome reflects the presence of left ventricular inflow and outflow obstruction. The infant is tachypneic and is in moderate to severe respiratory distress, depending on the severity of the inflow obstruction. The pulses in the lower extremities may be normal immediately after birth, although within the first few days of life, the pulses decrease in conjunction with closure of the ductus arteriosus and development of obstruction at the coarctation site. Upper body oxygen saturations are nearly normal, but lower body saturations may be decreased because of a right-to-left ductal shunt. The liver is enlarged. The precordium is active. The pulmonic component of the second heart sound is increased but usually cannot be separated from the aortic component. A harsh mid- to high-frequency systolic murmur is heard best in the retrosternal area and radiates to the apex and to the neck. Despite the abnormality of the aortic valve, a systolic ejection click is rarely heard, likely because of the subaortic obstruction, the small aortic annulus, and the rapid heart rate. A mid-diastolic murmur is present at the apex and reflects mitral stenosis, although this may be difficult to hear in a neonate.

Ancillary Tests

• The chest radiograph shows pulmonary edema and left atrial enlargement, sometimes with diffuse cardiomegaly if the coarctation is severe.

• The electrocardiogram changes over time. During the first days of life, it may be normal, but right ventricular hypertrophy develops rapidly; later, left atrial enlargement and, subsequently, left ventricular hypertrophy are present.

• Echocardiography defines the anatomy and the presence of obstruction at the mitral valve, subaortic area, aortic valve, and aorta. However, when multiple levels of obstruction are present, it is extremely difficult to ascertain the relative hemodynamic severity at each site of obstruction.

Therapeutic Considerations

The major decision in infants with Shone syndrome is whether a surgical approach can maintain two separate circulations perfused by separate ventricles. If not, a single ventricle palliation strategy or heart transplantation are the surgical options. If both upper and lower body oxygen saturations are normal in the presence of adequate systemic perfusion, the left ventricle must be providing all of the flow into the systemic arterial bed. In this case, once the obstruction is removed, the left ventricle should be sufficient for normal systemic output. In contrast, if the oxygen saturation in the lower portion of the body is decreased, part of the systemic flow to the lower body is being provided by the right ventricle through the ductus arteriosus. In that case, it is uncertain whether the left ventricle will be capable of supporting the systemic circulation after surgical repair. In either situation, however, careful consideration of other findings is necessary before making final recommendations regarding the most appropriate initial type of intervention.

Careful evaluation of the echocardiogram is very important. The mitral valve should be completely evaluated for the presence of a supravalvar ring, mitral annulus size, leaflet morphology, and chordae and papillary muscle anatomy and attachment. A hypoplastic mitral valve annulus precludes a two-ventricle repair, and a Norwood procedure is indicated (see following text). The Doppler velocity across the foramen ovale yields an approximate left atrial mean pressure (above right atrial mean pressure). The subaortic region should be evaluated for its size and the site and cause of obstruction. The size of the left ventricle should be carefully measured. An abnormal mitral valve attachment causing subaortic obstruction is very difficult to approach surgically, and a very narrow left ventricular outflow tract may be an indication for a modified Konno surgical procedure. In this procedure, the left ventricular outflow tract is enlarged by opening and enlarging the ventricular septum into the right ventricular outflow tract, and then a patch is used to augment the anterior outflow of the right ventricle. The degree of valvar aortic stenosis is extremely difficult to ascertain because of the proximal subaortic obstruction, but it is rarely severe. The aortic arch and isthmus are important to evaluate thoroughly to exclude a hypoplastic aortic arch and a coarctation of the aorta, both of which may require early surgical intervention. The presence of a large patent ductus arteriosus may make evaluation of the area of the potential coarctation difficult. Retrograde flow in the aortic arch during systole suggests that the left ventricle cannot supply even the upper body with adequate flow, and thus a two-ventricle repair is probably not possible.

Hypoplastic Left Heart Syndrome

Anatomic and Physiologic Considerations

Hypoplastic left heart syndrome is the most common and severe congenital heart defect that presents with inadequate systemic perfusion shortly after birth. In utero, the fetus develops normally because the right ventricle takes over the work of both ventricles by ejecting all of the combined venous return into the main pulmonary artery to perfuse the upper and lower portions of the body through the ductus arteriosus (Chapter 3, Figure 3-5). Normally, about one-third of combined ventricular output passes through the foramen ovale from the right to the left atrium. In the presence of hypoplastic left heart syndrome, a much smaller amount of blood, representing pulmonary venous return, passes from the left to the right atrium. Thus, the foramen ovale and the left atrium are relatively small structures, and restriction to flow through the left atrium to the right after birth may become apparent, as pulmonary blood flow increases greatly.

Rarely, the foramen ovale is restrictive in utero, which causes left atrial hypertension, increased pulmonary arteriolar muscle, pulmonary lymphangiectasia, and pulmonary venous thickening during fetal life. Abnormal pulmonary venous flow patterns are present in such fetuses characterized by significant flow reversal in the pulmonary veins (Figure 8-7). These fetuses may have hydrops fetalis, but if not, they are critically ill immediately after birth, showing signs of severe pulmonary arterial hypertension, pulmonary edema, and hypoperfusion, similar to newborns with total anomalous pulmonary venous connection with critical obstruction. Their prognosis is extremely poor. Attempts at relief of the obstruction in utero with atrial septal dilation or stent placement and postnatally with balloon atrial septostomy or atrial septectomy have met with limited success.

Clinical Presentation

Infants with hypoplastic left heart syndrome and a restrictive foramen ovale present within the first hours after birth with severe respiratory distress, cyanosis, and decreased systemic perfusion. Most infants, however, have an adequate foramen ovale after birth and therefore do not develop symptoms until the ductus arteriosus begins to close. Within hours or days of birth, tachypnea with respiratory distress become apparent, feeding is impaired, heart rate increases, the pulses become more difficult to palpate, and the infant appears pale and poorly perfused. The oxygen saturations are modestly decreased, usually in the high 80s to low 90s, because pulmonary blood flow is much higher than systemic blood flow. These clinical findings are similar to those in infants with septic shock, which is often considered the primary diagnosis. It is essential to consider the possibility of hypoplastic left heart syndrome in every neonate in whom sepsis is considered as the most likely diagnosis. As metabolic acidosis progresses in infants with hypoplastic left heart syndrome, the degree of tachypnea and tachycardia increases, the precordium becomes hyperactive, and hepatomegaly becomes apparent. The first heart sound is normal, and the second heart sound is single and often loud. Murmurs are not an important component of the clinical findings, but a 2-3/6 medium-frequency murmur at the lower left sternal border of tricuspid regurgitation or a soft axillary or infraclavicular murmur of the ductus arteriosus or pulmonary arterial flow may be audible. Without appropriate treatment, blood pressure progressively falls, perfusion further decreases, and the infant usually dies within hours or days of presentation.

FIGURE 8-6. Cor triatriatum. The pulmonary venous confluence comes in close enough contact with the left atrium to create a single chamber but with incomplete coalescence. The pulmonary veins usually enter the accessory chamber that is connected to the left atrium by an opening of variable size. Although the anatomy may be variable, the more distal true left atrium usually communicates with the left atrial appendage and the foramen ovale.

FIGURE 8-7. In utero pulmonary venous Doppler in hypoplastic left heart syndrome. Note that the flow is reversed in atrial systole in the pulmonary veins, indicative of severe obstruction to the egress of blood from the left atrium, via both the mitral valve and the foramen ovale.

Ancillary Tests

• The chest radiograph shows diffuse moderate cardiomegaly and increased vascularity, particularly in the hilar region due to pulmonary venous congestion.

• The electrocardiogram shows decreased left-sided forces, with pure R waves in the right precordium and no septal Q waves in the left precordium. Signs of right ventricular hypertrophy often are not present until several days of age, when the normal inversion of the right precordial T waves does not occur. Occasionally, inversion of T waves is seen across all precordial leads, thought to be related to inadequate perfusion of the right ventricular myocardium. P waves are often tall and peaked in limb leads II and III and in the right precordial leads, indicative of right atrial enlargement.

• The echocardiogram usually is immediately diagnostic, most frequently showing a diminutive and fibrotic left ventricle with a very hypoplastic aortic valve (Figure 8-8). The ascending aorta is of variable size, often only a tiny vessel of 1 to 2 mm in diameter that functions only as a conduit for the coronary arteries. Doppler interrogation shows retrograde flow in the ascending aorta. Careful evaluation should be made for right ventricular dysfunction, the presence and severity of tricuspid insufficiency, and restriction of flow across the foramen ovale, ductus arteriosus, or aortic isthmus. The presence of pleural effusions should raise concern for the presence of Turner syndrome.

FIGURE 8-8. Postnatal echocardiogram of hypoplastic left heart syndrome. The echocardiogram shows a severely hypoplastic left ventricle, aortic atresia, and a diminutive ascending aorta.

Therapeutic Considerations

Rapid intervention to stabilize these infants is required to prevent or reverse severe respiratory, hemodynamic, and metabolic decompensation. The infant may require intubation, ventilation, and sedation to minimize the oxygen consumption associated with increased respiratory work and to resolve pulmonary edema. Immediate intravenous access must be obtained in order to infuse prostaglandin E1 to maintain patency of the ductus arteriosus, inotropic agents if right ventricular function is impaired, and appropriate volume or vasodilator therapy. Adjustment of afterload to maintain adequate perfusion of the various organ beds is often a delicate balance because prostaglandin E1 infusion tends to vasodilate the systemic arterial vasculature, thereby decreasing perfusion pressure; volume infusion may therefore be required. Right ventricular dysfunction and tricuspid insufficiency may improve by administration of an inodilator such as milrinone to decrease afterload. Finally, any significant metabolic derangement must be corrected. Once stabilized, it is often possible to extubate the infant while awaiting intervention, but it is important to ensure a reasonable balance of systemic and pulmonary blood flow. Because of the low pulmonary vascular resistance, pulmonary blood flow is often excessively high at the expense of systemic blood flow, even with a widely patent ductus arteriosus. To minimize this imbalance, the infant should not be in supplemental oxygen, and permissive hypercapnia may be necessary to increase pulmonary vascular resistance. In addition, the hematocrit should be maintained at a high level, at least 45%, to ensure adequate systemic oxygen delivery and to maximize pulmonary vascular resistance relative to systemic.

Surgical management of these patients requires a special approach because, unlike other lesions with only a single functional ventricle, both the aortic valve and the aorta are hypoplastic. Thus, they cannot be managed initially with just a shunt or pulmonary artery band. The initial reconstructive palliation (modified Norwood procedure) offers a way to provide adequate systemic blood flow (Figure 8-9A, B). The main pulmonary artery is transected just below the bifurcation, opened longitudinally, and sewn together with the opened ascending aorta (often with homograft tissue augmentation). This enlarges the hypoplastic ascending aorta and establishes a connection between the proximal pulmonary artery and the descending aorta. There is usually a coarctation, so the aortoplasty is extended distal to the area of coarctation. The area where the main pulmonary artery was attached to the branches is patched and then is reattached to the circulation either via a modified Blalock-Taussig shunt (Figure 8-8A) or via a right ventricle-to-pulmonary artery conduit (Figure 8-8B). An atrial septectomy is usually performed to ensure unobstructed blood flow from the pulmonary veins to the right ventricle. After this surgery, the systemic venous return enters the right atrium and then flows through the right ventricle and the original pulmonary valve (now the neo-aortic valve) to the neoaorta and systemic circulation. Blood flows to the lungs through the shunt or conduit. The pulmonary venous return flows through the left atrium across a mandatory atrial septal defect to the right atrium, right ventricle, and neo-aorta. The coronary arteries are left connected to the original hypoplastic aorta and are perfused in a retrograde manner from the main pulmonary artery.

FIGURE 8-9. Various approaches to first-stage palliation of patients with hypoplastic left heart syndrome. A and B. In the surgical reconstructive approach, the main pulmonary artery, augmented by a homograft patch, is sewn to the native hypoplastic ascending aorta, creating the neo-aorta. Pulmonary blood flow is supplied by a modified Blalock-Taussig shunt in A and by a right ventricle-to-pulmonary artery conduit in B. C. In this variant of the “hybrid” procedure, the ductus arteriosus is stented open using a direct approach via the main pulmonary artery, and the bilateral branch pulmonary arteries are surgically banded. Abbreviations: RV, right ventricle; PA, pulmonary artery. Reproduced with permission from Pediatrics. 119(1):109-117, ©2007 by the AAP.

These patients are always critically ill immediately after surgery. Particular attention should be focused on maintaining the correct balance between systemic and pulmonary blood flows. The modified Blalock-Taussig shunt provides continuous forward flow into the pulmonary arteries and is associated with diastolic retrograde flow in the descending aorta and coronary arteries. Because myocardial perfusion occurs primarily during diastole, this retrograde coronary blood flow (“coronary steal”) may result in myocardial ischemia and circulatory instability. In contrast, coronary arterial flow patterns are not perturbed in patients with a right ventricle-to-pulmonary artery conduit. However, this approach also has potential disadvantages, including a negative impact on right ventricular function, arrhythmias, or aneurysm formation related to the ventriculotomy and decreased growth of the pulmonary arteries.

Outcomes in 555 infants randomized to either the modified Blalock-Taussig shunt or the right ventricle-to-pulmonary artery conduit were evaluated in a trial conducted by the Pediatric Heart Network at 15 North American centers. Transplant-free survival 12 months after surgery was significantly higher for patients who received the right ventricle-to-pulmonary artery conduit than that for those who received the modified Blalock-Taussig shunt. However, the need for unintended interventions and complications was higher in the patients with the conduits. Additionally, intermediate-term data showed no significant difference in transplant-free survival between the two groups of patients beyond 12 months. Ongoing follow-up of these patients is necessary to determine if either a shunt or a conduit is superior in the long term.

Rather than this surgical approach, which requires aorto-pulmonary bypass and aortic arch reconstruction, a “hybrid” procedure consisting of a combination of nonbypass surgery and interventional catheterization is performed in some centers, particularly when surgical risk is high because of associated defects or organ injury (Figure 8-8C). There are various modifications of the hybrid procedure, but all aim to ensure unimpeded systemic blood flow by placement of stents in the ductus arteriosus and occasionally in the aortic isthmus and control of pulmonary blood flow by the placement of bilateral pulmonary arterial bands. If the foramen ovale is restrictive, a stent is also placed across the atrial septum. In these cases, reconstruction of the aortic arch is delayed.

The next step of this palliation is a superior cavopulmonary anastomosis (also known as the bidirectional Glenn anastomosis) as described in Chapter 6. The arch is reconstructed at this time if the patient previously underwent a hybrid procedure. The shunt or conduit is taken down to maximize volume unloading of the ventricle. The third step of this palliation is a modified Fontan operation, performed typically at age 15 to 30 months (Chapter 6).

Rarely, the left ventricle is of reasonable size, almost apex forming. This occurs when the mitral valve is fairly well developed and there is patency of the aortic valve, representing a middle position in the continuum between hypoplastic left heart syndrome and critical valvar aortic stenosis (see following text). Indeed, there is now strong genetic evidence that hypoplastic left heart syndrome, valvar aortic stenosis, and bicuspid aortic valve without stenosis are levels of severity in the expression of the same genetic defect(s) (Chapter 1). In the situation in which the mitral valve and left ventricle are relatively well developed, it can be very difficult to decide whether to attempt a biventricular repair. Such an approach often necessitates a Ross-Konno procedure, in which the outflow tract is enlarged anteriorly into the right ventricle, the aortic valve is replaced with the native pulmonary valve, and a right ventricle-to-pulmonary artery homograft replaces the native pulmonary valve. A number of variables have been used in an attempt to determine whether the left ventricle will be capable of supporting systemic blood flow after surgery, but the most important ones are the size and function of the mitral valve and the capacity of the left ventricle. In this regard, the function of the left ventricle cannot be evaluated adequately preoperatively because it is ejecting against an extremely high afterload imposed by the severely obstructed aortic valve. However, the presence of a very bright endocardium on echocardiography is of concern because it suggests fibrosis, which may not allow the left ventricle to fill under adequately low pressures after surgery. When uncertain, it is possible to perform an initial Norwood palliation procedure in the newborn and later convert the infant to a two-ventricle circulation by takedown of the ascending aortic anastomosis with the main pulmonary artery and repair of the left ventricular outflow tract.

Valvar Aortic Stenosis

Anatomic and Physiologic Considerations

Isolated valvar aortic stenosis (in the presence of a normal mitral valve and normal-size left ventricle) is a relatively common isolated defect, but it only occasionally presents as critical, or symptomatic, disease in the newborn infant. Critical aortic stenosis is much less common than is hypoplastic left heart syndrome. The majority of the stenotic valves are bicuspid rather than tricuspid. Most bicuspid aortic valves are not obstructive, at least until later years, when the valve may become calcified. When the valve creates a critical degree of outflow obstruction in the newborn infant, it is usually very thick and dysplastic and may be unicuspid. In the newborn with critical aortic stenosis, a right-to-left shunt across the ductus arteriosus is necessary to maintain adequate systemic perfusion. A large left- to-right shunt across the foramen ovale is present because of the increased diastolic pressure in the obstructed left ventricle (Figure 8-10). This raises the oxygen saturation in the right ventricle and pulmonary artery greatly, and this relatively highly saturated blood both returns back to the lungs and flows right to left through the ductus arteriosus.

Severe aortic stenosis is being diagnosed with increasing frequency in the fetus. It has been shown to progress to hypoplastic left heart syndrome as the fetus advances toward term, providing further evidence that primary defects of the aortic valve represent a large continuum of clinical expression of the same genetic defect(s). Because of these findings, fetal intervention is offered in some centers. Unfortunately, there is yet no evidence that this approach has a positive impact on outcome in the majority of infants (Chapter 4).

FIGURE 8-10. Critical valvar aortic stenosis. Because left ventricular end-diastolic pressure is very high, a large left-to-right shunt through the foramen ovale occurs. This shunt markedly increases right ventricular and pulmonary arterial oxygen saturation, which causes the descending aortic oxygen saturation to be relatively high despite a large right-to-left ductal shunt. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Clinical Presentation

The infant with critical aortic stenosis presents with tachypnea and respiratory distress caused by markedly increased left atrial pressure and resulting pulmonary edema. A history of poor feeding and frequent emesis is often present. It may be difficult to clinically distinguish critical aortic stenosis from hypoplastic left heart syndrome, but pulse oximetry is usually helpful. In patients with critical aortic stenosis, pulse oximetry usually shows a higher saturation in the upper extremities as compared to the lower because the left ventricle is capable of ejecting blood to the upper body, whereas saturations are the same in all extremities in patients with hypoplastic left heart syndrome, in which the aortic valve is atretic or nearly so. The pulses are decreased in all extremities, and perfusion is poor. The liver is often enlarged. The precordium is diffusely hyperactive because much of the increased impulse is caused by the volume and pressure load on the right ventricle. The first heart sound is normal, and the second heart sound is often difficult to appreciate splitting because of the marked tachycardia. Despite the dysplastic aortic valve, an audible ejection click is rare because valve excursion is usually markedly reduced due to severe dysplasia and low output across the valve. An S3 gallop is frequently heard at the apex. A harsh systolic ejection murmur may be heard best at the upper retrosternal area and radiates to the apex and the carotids. However, in patients with severe obstruction, the murmur may be absent or barely audible because of the very small amount of blood actually crossing the aortic valve.

Ancillary Tests

• The chest radiograph shows cardiomegaly, prominent vascular markings, and venous congestion.

• The electrocardiogram usually shows left ventricular hypertrophy and diffuse ST-T wave abnormalities, either flattening or inversion, which is suggestive of subendocardial ischemia. Occasionally, dominant right-sided forces with right axis deviation are seen, but unlike in hypoplastic left heart syndrome, a septal Q wave and R waves in the left precordium are present. Left atrial enlargement may also be present.

• The echocardiogram is used to define the size of the left ventricle, the degree of myocardial dysfunction, the presence of endocardial fibrosis, the size of the aortic annulus, and the anatomy of the valve. Patency of the ductus arteriosus is determined, and the aortic arch is carefully evaluated for associated coarctation of the aorta, though this rarely occurs. If the atrial communication is restrictive, the Doppler velocity can be used to approximate left atrial pressure.

Therapeutic Considerations

Supportive care is provided according to the degree of decompensation and impairment of systemic blood flow. An infusion of prostaglandin E1 should be initiated to maintain ductal patency and flow from the pulmonary artery to the descending aorta. As with hypoplastic left heart syndrome, it must be decided whether it is possible to create a two-ventricle circulation. In the case of critical aortic stenosis, the problem is rarely the size of the ventricular cavity; instead, the major concern is related to the function of the left ventricle. If the ventricle is severely fibrotic and cannot generate high pressures when obstructed, it may not be capable of supporting systemic blood flow even after the obstruction is relieved. Doppler studies can be helpful in this regard—the simultaneous pressure difference between the left ventricle and aorta can be measured, and an estimate of the peak left ventricular pressure can be obtained from the peak velocity of a jet of mitral insufficiency. In the catheterization laboratory, left ventricular peak systolic pressure and the peak systolic pressure difference between the left ventricle and the aorta should be determined before a decision regarding balloon aortic valvuloplasty is made.

Balloon aortic valvuloplasty is generally the preferred approach for alleviating the obstruction in most cases, but a surgical approach may also be considered. If the ventricle is contracting at infrasystemic pressures or cannot generate a peak systolic pressure gradient of more than about 20 mm Hg because of severe dysfunction, it likely will not be able to generate adequate pressure once the obstruction is relieved. In this situation, a staged palliative surgical reconstruction approach (eg, Norwood procedure) rather than a balloon aortic valvuloplasty may be warranted. If it is uncertain whether the left ventricle will be an adequate systemic ventricle, a hybrid approach (see earlier text) may be the best initial therapeutic approach, as this is less invasive than the Norwood procedure and more easily converted to a two-ventricle circulation later in infancy.

The newborn infant with severe but not critical aortic stenosis (ie, there is no hemodynamic decompensation in the absence of a ductus arteriosus and ventricular systolic function is normal) presents a therapeutic dilemma.

The infant is hemodynamically stable, but demands on the myocardium over the first weeks of life are large. In addition to the large increase in metabolic demand after birth, hemoglobin levels decrease in the first weeks of life, necessitating a further increase in output. Moreover, anemia causes systemic vasodilation, which decreases aortic diastolic pressure and causes tachycardia. The low diastolic pressure, in association with tachycardia and the increased end-diastolic pressure of the hypertrophied ventricle, may further diminish coronary blood flow reserve. Rapid ventricular dysfunction may occur weeks after birth. If the ventricle fails because of myocardial ischemia, ventricular function may not recover when the obstruction is relieved. Thus, the decision as to whether a newborn infant should undergo a balloon aortic valvuloplasty or surgery at birth must be made not only in the infant with critical aortic stenosis but also in the infant with severe aortic stenosis. If therapy is delayed, it is extremely important that the infant be followed closely for any evidence of decompensation. Onset of even subtle symptoms should prompt intervention to relieve the aortic obstruction.

Interruption of the Aortic Arch

Anatomic and Physiologic Considerations

Interruption of the aortic arch occurs almost exclusively in association with other congenital heart defects, such as a posteriorly malaligned ventricular septal defect, an aorto-pulmonary window, or truncus arteriosus. The interruption occurs most frequently between the left carotid and left subclavian arteries (type B); this is the type that occurs in association with ventricular septal defects and truncus arteriosus. This condition is likely part of an embryologic abnormality in arch development, and the majority of these infants have microdeletion 22q11 syndrome. In fact, interrupted aortic arch is more highly associated with a microdeletion of chromosome 22 than any other cardiovascular defect (Chapter 15).

Because interrupted aortic arch presents in association with many of the defects already discussed and because its impact on the presentation of the heart defect is similar to that of coarctation of the aorta, the clinical presentation will be discussed with coarctation of the aorta.

Coarctation of the Aorta

Anatomic and Physiologic Considerations

Coarctation of the aorta is a common congenital cardiovascular defect, occurring either in isolation or in association with other defects, most commonly a ventricular septal defect and/or a bicuspid aortic valve. The association of coarctation of the aorta and bicuspid aortic valve is extremely high (>60%) regardless of whether coarctation is an isolated defect or occurs in conjunction with other defects. Although coarctation of the aorta may occur as a part of a developmental defect in infants with embryological truncal and arch abnormalities, it seems that it is more often secondary to abnormalities of flow. For example, coarctation of the aorta is associated not only with a posterior malaligned ventricular septal defect, as is interruption of the aortic arch, but also with muscular ventricular septal defects. In these cases, coarctation may result from decreased flow around the aortic isthmus, caused by redirection of some of the output of the left ventricle to the right ventricle and main pulmonary artery in utero. With the increasing use of fetal echocardiography, it is apparent that there is a high incidence of ventricular septal defects during fetal life and that many of these defects close spontaneously. It is possible that isolated coarctation of the aorta may not actually be isolated but may have been initially associated with a ventricular septal defect that subsequently closed in utero. Also, the high incidence of a bicuspid aortic valve may be a predisposing factor. The abnormal valve may cause a flow disturbance in the ascending aorta and aortic arch, and thus development of the distal end of the aortic isthmus where ductal flow arises may be disrupted, causing a posterior shelf that becomes obstructive. Alternatively, bicuspid aortic valve may be associated with a diffuse aortopathy, and it is possible that this aortopathy predisposes the fetus to develop a coarctation of the aorta.

Clinical Presentation

The timing of the clinical presentation of patients with coarctation of the aorta is quite different than that of hypoplastic left heart syndrome. Because the left ventricle and ascending aorta are normally formed in coarctation, symptoms of obstruction occur only when the distal part of the arch, the aortic isthmus (that portion of the aorta between the left subclavian artery and the origin of the ductus arteriosus), becomes critically obstructed. The ductus arteriosus closes initially at its pulmonary arterial end, and then closure progresses to the aorta (Figure 8-1). Thus, even functional closure does not necessarily cause significant obstruction. It is not until complete anatomic closure occurs that most infants with coarctation of the aorta present with decreased perfusion to the lower body.

This may be delayed for 1 to 3 weeks, so it is important to be aware that a normal examination in the first few days of life does not preclude the presence of significant coarctation of the aorta.

The clinical findings depend on the severity of decreased systemic perfusion at the time of presentation. Ideally, the diagnosis is made during the first few days of life, when the infant is clinically well but is found to have decreased pulses in the lower extremities. Dorsalis pedis and posterior tibial pulses are generally easy to palpate in infants because these arteries are superficially located and are easily felt over the underlying bones. In contrast, femoral pulses are often difficult to feel in the newborn infant because the femoral arteries are deeper and the hips must be abducted. Because collateral vessels around a coarctation develop over months or years after birth, radio-femoral delay is not present in the newborn infant with a coarctation of the aorta.

If there is any suggestion of decreased lower extremity pulses, blood pressures should be measured. It is best to measure the right arm and either leg systolic blood pressures simultaneously. If a blood pressure difference is not identified but the lower extremity pulses seem decreased, it is important to consider the possibility of a right aortic arch and then to measure the left arm and either leg pressures. If these measurements are also equal, the possibility should be considered that the infant has a left aortic arch with an anomalous right subclavian artery, an anatomic variant that is even more common than coarctation with a right aortic arch. In this situation both subclavian arteries are distal to the region of coarctation. The lack of a systolic pressure difference should lead the clinician to palpate the carotid arteries carefully; the carotid pulses should be very strong in the presence of decreased upper and lower extremity pulses in a patient with coarctation of the aorta and an anomalous right subclavian artery.

A blowing systolic murmur is frequently heard in the axilla and back, and a mid-diastolic murmur is audible at the apex, even in the absence of a mitral valve abnormality. If a bicuspid aortic valve is also present, a systolic ejection click and a systolic ejection murmur may be heard at the base.

If lower body perfusion is decreased for several hours, metabolic acidosis will develop, and the infant will become tachypneic. Although the newborn heart is relatively insensitive to acidosis, the left ventricle will eventually begin to fail as the acidosis progresses and afterload increases. At this point, left ventricular end-diastolic pressure begins to increase, and pulmonary edema develops. The infant then becomes distressed, with intercostal and subcostal retractions, nasal flaring, and grunting. At this time, the lower extremities become cool, and capillary refill is prolonged as perfusion decreases. Soon thereafter, further left ventricular dysfunction develops, and even the upper body pulses become decreased. It is at this point in the progression of the disease that the diagnosis may be missed because the pulse and the blood pressure differentials become obscured.

Resuscitative measures must be undertaken immediately without waiting for definitive diagnosis. Endotracheal intubation and assisted ventilation, inotropic support, correction of acidosis, and infusion of prostaglandin E₁ all must be started as soon as possible. Since infants with septic shock may present with the same clinical findings, cultures should be obtained, and antibiotic therapy should be initiated. If the infant with aortic coarctation is managed rapidly and appropriately, the upper body pulses rapidly improve, and the diagnosis becomes more obvious.

Ancillary Tests

• Chest radiography may be normal initially, but cardiomegaly and venous congestion develop as the infant deteriorates.

• The electrocardiogram is normal within the first few days of life, but eventually the T waves fail to invert, indicating right ventricular hypertrophy. Diffuse ST-segment depression may be present and reflects myocardial strain. The right ventricle is hypertrophied because it is ejecting through the ductus arteriosus at the coarctation site initially and because pulmonary arterial pressures remain increased. Within a week or two after birth, left ventricular hypertrophy also develops because of increased afterload. Thereafter, left atrial enlargement becomes evident.

• The definitive diagnosis is made by echocardiography, but a high level of skill and experience is necessary to obtain adequate images of the aorta for diagnosis. It can be difficult to assess for coarctation in the presence of a widely patent ductus arteriosus. If the posterior shelf is not apparent, pulsed wave and color Doppler studies may demonstrate the accelerated, disturbed flow through the area and a slow upstroke in the descending aorta. A right-to-left ductal shunt may also be apparent. It is important to carefully evaluate the head and neck vessels, particularly the origin of the right subclavian artery, and the aortic arch, which is often hypoplastic. The aortic valve, subaortic region, and the ventricular septum also should be evaluated. In some cases, the anatomy is difficult to define completely by echocardiography. If so, magnetic resonance imaging can be used and is extremely helpful in defining the anatomy of the aorta, arch vessels, ductus arteriosus, and site of coarctation.

Therapeutic Considerations

Surgical repair of the aorta and other associated defects is always indicated. Infants who present with shock and metabolic acidosis because of coarctation of the aorta or interrupted aortic arch can be stabilized by administration of prostaglandin E1 and other supportive care. These infants are likely to have sustained end-organ damage because of decreased systemic perfusion. Deferring surgery for several days to allow recovery of renal and hepatic function decreases surgical morbidity and mortality. The presence of aortic arch hypoplasia often requires extension of the surgical repair along the undersurface of the arch to the carotid artery using an anterior sternotomy approach rather than the usual left thoracotomy.