Chapter 20: Cardiovascular Diseases

Eight in 1000 infants are born with a congenital heart defect. Advances in medical and surgical care allow more than 90% of such children to enter adulthood. Pediatric cardiac care includes not only the diagnosis and treatment of congenital heart disease but also the prevention of risk factors for adult cardiovascular disease—obesity, smoking, and hyperlipidemia. Acquired and familial heart diseases such as Kawasaki disease (KD), viral myocarditis, cardiomyopathies, and rheumatic heart disease are also a significant cause of morbidity and mortality in children.

HISTORY

Symptoms related to congenital heart defects primarily vary according to the alteration in pulmonary blood flow (Table 20–1). The presence of other cardiovascular symptoms such as palpitations and chest pain should be determined by history in the older child, paying particular attention to the timing (at rest or activity-related), onset, and termination (gradual vs sudden), as well as precipitating and relieving factors.

PHYSICAL EXAMINATION

General

The examination begins with a visual assessment of mental status, signs of distress, perfusion, and skin color. Documentation of heart rate, respiratory rate, blood pressure (in all four extremities), and oxygen saturation is essential. Many congenital cardiac defects occur as part of a genetic syndrome (Table 20–2), and complete assessment includes evaluation of dysmorphic features that may be clues to the associated cardiac defect.

Cardiovascular Examination

A. Inspection and Palpation

Chest conformation should be noted in the supine position. A precordial bulge indicates cardiomegaly. Palpation may reveal increased precordial activity, right ventricular (RV) lift, or left-sided heave; a diffuse point of maximal impulse; or a precordial thrill caused by a grade IV/VI or greater murmur. The thrill of aortic stenosis is found in the suprasternal notch. In patients with severe pulmonary hypertension (PH), a palpable pulmonary closure (P₂) is frequently noted at the upper left sternal border.

B. Auscultation

1. Heart sounds

The first heart sound (S₁) is the sound of atrioventricular (AV) valve closure. It is best heard at the lower left sternal border and is usually medium pitched. Although S₁ has multiple components, only one of these (M₁—closure of the mitral valve) is usually audible.

The second heart sound (S₂) is the sound of semilunar valve closure. It is best heard at the upper left sternal border. S₂ has two component sounds, A₂ and P₂ (aortic and pulmonic valve closure). Splitting of S₂ varies with respiration, widening with inspiration and narrowing with expiration. Abnormal splitting of S₂ may be an indication of cardiac disease (Table 20–3). A prominent or loud P₂ is associated with PH.

The third heart sound (S₃) is the sound of rapid left ventricular (LV) filling. It occurs in early diastole, after S₂, and is medium- to low-pitched. In healthy children, S₃ diminishes or disappears when going from supine to sitting or standing. A pathologic S₃ is often heard in the presence of poor cardiac function or a large left-to-right shunt. The fourth heart sound (S₄) is associated with atrial contraction and increased atrial pressure and has a low pitch similar to that of S₃. It occurs just prior to S₁ and is not normally audible. It is heard in the presence of atrial contraction into a noncompliant ventricle as in hypertrophic or restrictive cardiomyopathy or from other causes of diastolic dysfunction.

Ejection clicks are usually related to dilate great vessels or valve abnormalities. They are heard during ventricular systole and are classified as early, mid, or late. Early ejection clicks at the mid-left sternal border are from the pulmonic valve. Aortic clicks are typically best heard at the apex. In contrast to aortic clicks, pulmonic clicks vary with respiration, becoming louder during inspiration. A mid to late ejection click at the apex is most typically caused by mitral valve prolapse (MVP).

2. Murmurs

A heart murmur is the most common cardiovascular finding leading to a cardiology referral. Innocent or functional heart murmurs are common, and 40%–45% of children have an innocent murmur at some time during childhood.

A. CHARACTERISTICS—All murmurs should be described based on the following characteristics:

(1) Location and radiation—Where the murmur is best heard and where the sound extends.

(2) Relationship to cardiac cycle and duration—Systolic ejection (immediately following S₁ with a crescendo/decrescendo change in intensity), pansystolic (occurring throughout most of systole and of constant intensity), diastolic, or continuous. The timing of the murmur provides valuable clues as to the underlying pathology (Table 20–4).

(3) Intensity—Grade I describes a soft murmur heard with difficulty; grade II, soft but easily heard; grade III, loud but without a thrill; grade IV, loud and associated with a precordial thrill; grade V, loud, with a thrill, and audible with the edge of the stethoscope; grade VI, very loud and audible with the stethoscope off the chest.

(4) Quality—Harsh, musical, or rough; high, medium, or low in pitch.

(5) Variation with position—Audible changes in murmur when the patient is supine, sitting, standing, or squatting.

B. INNOCENT MURMURS—The six most common innocent murmurs of childhood are as follows:

(1) Newborn murmur—Heard in the first few days of life, this murmur is at the lower left sternal border, without significant radiation. It has a soft, short, vibratory grade I–II/VI quality that often subsides when mild pressure is applied to the abdomen. It usually disappears by age 2–3 weeks.

(2) Peripheral pulmonary artery stenosis (PPS)—This murmur, often heard in newborns, is caused by the normal branching of the pulmonary artery. It is heard with equal intensity at the upper left sternal border, at the back, and in one or both axillae. It is a soft, short, high-pitched, grade I–II/VI systolic ejection murmur and usually disappears by age 2. This murmur must be differentiated from true peripheral pulmonary stenosis (Williams syndrome, Alagille syndrome, or rubella syndrome), coarctation of the aorta, and valvular pulmonary stenosis. Characteristic facial features, extracardiac physical examination findings, history, and laboratory abnormalities suggestive of the syndromes listed above are the best way to differentiate true peripheral pulmonary stenosis from benign PPS of infancy as the murmurs can be similar.

(3) Still murmur—This is the most common innocent murmur of early childhood. It is typically heard between 2 and 7 years of age. It is the loudest midway between the apex and the lower left sternal border. Still murmur is a musical or vibratory, short, high-pitched, grade I–III early systolic murmur. It is loudest when the patient is supine. It diminishes or disappears with inspiration or when the patient is sitting. The still murmur is louder in patients with fever, anemia, or sinus tachycardia from any reason.

(4) Pulmonary ejection murmur—This is the most common innocent murmur in older children and adults. It is heard from age 3 years onward. It is usually a soft systolic ejection murmur, grade I–II in intensity at the upper left sternal border. The murmur is louder when the patient is supine or when cardiac output is increased.

(5) Venous hum—A venous hum is usually heard after age 2 years. It is located in the infraclavicular area on the right. It is a continuous musical hum of grade I–III intensity and may be accentuated in diastole and with inspiration. It is best heard in the sitting position. Turning the child’s neck, placing the child supine, and compressing the jugular vein obliterates the venous hum. Venous hum is caused by turbulence at the confluence of the subclavian and jugular veins.

(6) Innominate or carotid bruit—This murmur is more common in the older child and adolescents. It is heard in the right supraclavicular area. It is a long systolic ejection murmur, somewhat harsh and of grade II–III intensity. The bruit can be accentuated by light pressure on the carotid artery and must be differentiated from all types of aortic stenosis. The characteristic findings of aortic stenosis are outlined in more detail later in this chapter.

When innocent murmurs are found in a child, the physician should assure the parents that these are normal heart sounds of the developing child and that they do not represent heart disease.

Extracardiac Examination

A. Arterial Pulse Rate and Rhythm

Cardiac rate and rhythm vary greatly during infancy and childhood, so multiple determinations should be made. This is particularly important for infants (Table 20–5) whose heart rates vary with activity. The rhythm may be regular, or there may be a normal phasic variation with respiration (sinus arrhythmia).

B. Arterial Pulse Quality and Amplitude

A bounding pulse is characteristic of runoff lesions, including patent ductus arteriosus (PDA), aortic regurgitation, arteriovenous malformation, or any condition with a low diastolic pressure (fever, anemia, or septic shock). Narrow or thready pulses occur in patients with conditions reducing cardiac output such as decompensated heart failure (HF) pericardial tamponade, or severe aortic stenosis. A reduction in pulse amplitude or blood pressure (> 10 mm Hg) with inspiration is referred to as pulsus paradoxus and is a sign of pericardial tamponade. The pulses of the upper and lower extremities should be compared. The femoral pulse should be palpable and equal in amplitude and simultaneous with the brachial pulse. A femoral pulse that is absent or weak, or that is delayed in comparison with the brachial pulse, suggests coarctation of the aorta.

C. Arterial Blood Pressure

Blood pressures should be obtained in the upper and lower extremities. Systolic pressure in the lower extremities should be greater than or equal to that in the upper extremities. The cuff must cover the same relative area of the arm and leg. Measurements should be repeated several times. A lower blood pressure in the lower extremities suggests coarctation of the aorta.

D. Cyanosis of the Extremities

Cyanosis results from an increased concentration (> 4–5 g/dL) of reduced hemoglobin in the blood. Bluish skin color is usually, but not always, a sign. Visible cyanosis also accompanies low cardiac output, hypothermia, and systemic venous congestion, even in the presence of adequate oxygenation. Cyanosis should be judged by the color of the mucous membranes (lips). Bluish discoloration around the mouth (acrocyanosis) does not correlate with cyanosis.

E. Clubbing of the Fingers and Toes

Clubbing is often associated with severe cyanotic congenital heart disease. It usually appears after age 1 year. Hypoxemia with cyanosis is the most common cause, but clubbing also occurs in patients with endocarditis, chronic liver disease, inflammatory bowel diseases, chronic pulmonary disease, and lung abscess. Digital clubbing may be a benign genetic variant.

F. Edema

Edema of dependent areas (lower extremities in the older child and the face and sacrum in the younger child) is characteristic of elevated right heart pressure, which may be seen with tricuspid valve pathology or HF.

G. Abdomen

Hepatomegaly is the cardinal sign of right HF in the infant and child. Left HF can ultimately lead to right HF, and therefore hepatomegaly may also be seen in the child with pulmonary edema from lesions causing left-to-right shunting (pulmonary overcirculation) or LV failure. Splenomegaly may be present in patients with long-standing HF, and is also a characteristic of infective endocarditis (IE). Ascites is a feature of chronic right HF. Examination of the abdomen may reveal shifting dullness or a fluid wave.

ELECTROCARDIOGRAPHY

The electrocardiogram (ECG) is essential for the evaluation of the cardiovascular system. The heart rate should first be determined, then the cardiac rhythm (Is the patient in a normal sinus rhythm or other rhythm as evidenced by a P wave with a consistent PR interval before every QRS complex?), and then the axis (Are the P and QRS axes normal for patient age?). Finally, assessment of chamber enlargement, cardiac intervals, and ST segments should be performed.

Age-Related Variations

The ECG evolves with age. The heart rate decreases and intervals increase with age. Right ventricle (RV) dominance in the newborn changes to left ventricle (LV) dominance in the older infant, child, and adult. The normal ECG of the 1-week-old infant is abnormal for a 1-year-old child, and the ECG of a 5-year-old child is abnormal for an adult.

Electrocardiographic Interpretation

Figure 20–1 defines the events recorded by the ECG.

A. Rate

The heart rate varies markedly with age, activity, and state of emotional and physical well-being (see Table 20–5).

B. Rhythm

Sinus rhythm should always be present in healthy children. Extra heartbeats representing premature atrial and ventricular contractions (PAC and PVC) are common during childhood, with atrial ectopy predominating in infants and ventricular ectopy during adolescence. Isolated premature beats in patients with normal heart structure and function are usually benign.

C. Axis

1. P-wave axis

The P wave is generated from atrial contraction beginning in the high right atrium at the site of the sinus node. The impulse proceeds leftward and inferiorly, thus leading to a positive deflection in all left-sided and inferior leads (II, III, and aVF) and negative in lead aVR.

2. QRS axis

The net voltage should be positive in leads I and aVF in children with a normal axis. In infants and young children, RV dominance may persist, leading to a negative deflection in lead I. Several congenital cardiac lesions are associated with alterations in the normal QRS axis (Table 20–6).

D. P Wave

In the pediatric patient, the amplitude of the P wave is normally no greater than 3 mm and the duration no more than 0.08 second. The P wave is best seen in leads II and V₁.

E. PR Interval

The PR is measured from the beginning of the P wave to the beginning of the QRS complex. It increases with age and with slower rates. The PR interval ranges from a minimum of 0.10 second in infants to a maximum of 0.18 second in older children with slow rates. Rheumatic heart disease, digitalis, β-blockers, and calcium channel blockers can prolong the PR interval.

F. QRS Complex

This represents ventricular depolarization, and its amplitude and direction of force (axis) reveal the relative ventricular mass in hypertrophy, hypoplasia, and infarction. Abnormal ventricular conduction (eg, right bundle-branch block [RBBB] or left bundle-branch block [LBBB]) is also revealed.

G. QT Interval

This interval is measured from the beginning of the QRS complex to the end of the T wave. The QT duration may be prolonged as a primary condition or secondarily due to drugs or electrolyte imbalances (Table 20–7). The normal QT duration is rate-related and must be corrected using the Bazett formula:

The normal QTc is less than or equal to 0.44 second.

H. ST Segment

This segment, lying between the end of the QRS complex and the beginning of the T wave, is affected by drugs, electrolyte imbalances, or myocardial injury.

I. T Wave

The T wave represents myocardial repolarization and is altered by electrolytes, myocardial hypertrophy, and ischemia.

CHEST RADIOGRAPH

Evaluation of the chest radiograph for cardiac disease should focus on (1) position of the heart, (2) position of the abdominal viscera, (3) cardiac size, (4) cardiac configuration, and (5) character of the pulmonary vasculature. The standard posteroanterior and left lateral chest radiographs are used (Figure 20–2).

Cardiac position is either levocardia (heart predominantly in the left chest), dextrocardia (heart predominantly in the right chest), or mesocardia (midline heart). The position of the liver and stomach bubble is either in the normal position (abdominal situs solitus), inverted with the stomach bubble on the right (abdominal situs inversus), or variable with midline liver (abdominal situs ambiguous). The heart appears relatively large in normal newborns at least in part due to a prominent thymic shadow. The heart size should be less than 50% of the chest diameter in children older than 1 year. The cardiac configuration on chest radiograph may provide useful diagnostic information (Table 20–8). Some congenital cardiac lesions have a characteristic radiographic appearance that suggests the diagnosis but should not be viewed as conclusive (Table 20–9). The pulmonary vasculature should be assessed. The presence of increased or decreased pulmonary blood flow suggests a possible congenital cardiac diagnosis, particularly in the cyanotic infant (Table 20–10).

Dextrocardia

Dextrocardia is a radiographic term used when the heart is on the right side of the chest. When dextrocardia occurs with reversal of position of the other important organs of the chest and abdomen (eg, liver, lungs, and spleen), the condition is called situs inversus totalis, and the heart is usually normal. When dextrocardia occurs with the other organs normally located (situs solitus), the heart usually has severe defects.

Other situs abnormalities include situs ambiguous with the liver central and anterior in the upper abdomen and the stomach pushed posteriorly, bilateral right-sidedness (asplenia syndrome), and bilateral left-sidedness (polysplenia syndrome). In virtually all cases of situs ambiguous, congenital heart disease is present.

ECHOCARDIOGRAPHY

Echocardiography is a fundamental tool of pediatric cardiology. Using multiple ultrasound modalities (two-dimensional imaging, Doppler, and M-mode), cardiac anatomy, blood flow, intracardiac pressures, and ventricular function can be assessed. Echocardiography is based on the physical principles of sound waves. The ultrasound frequencies utilized in cardiac imaging range from 2 to 10 million cycles/s.

M-mode echocardiography uses short bursts of ultrasound sent from a transducer. At acoustic interfaces, sound waves are reflected back to the transducer. The time it takes for the sound wave to return to the transducer is measured, and the distance to the interface is calculated. That calculated distance is displayed against time, and a one-dimensional image is constructed that demonstrates cardiac motion. Two-dimensional imaging extends this technique by sending a rapid series of ultrasound bursts across a 90-degree sector, which allows construction of a two-dimensional image of the heart. Doppler ultrasound measures blood flow. The ultrasound transducer sends out a known frequency of sound that reflects off moving red blood cells. The transducer receives the reflected frequency and compares it with the transmitted frequency. The blood flow velocity can be calculated from the measured frequency shift. This information is used to estimate pressure gradients by the simplified Bernoulli equation, in which the pressure gradient is equal to four times the calculated velocity (pressure gradient = 4(V²)).

A transthoracic echocardiogram is obtained by placing the transducer on areas of the chest where there is minimal lung interference. At each transducer position, the beam is swept through the heart and a two-dimensional image appears on the screen. Complex intracardiac anatomy and spatial relationships can be described, making possible the accurate diagnosis of congenital heart disease. In addition to structural details, Doppler gives information about intracardiac blood flow and pressure gradients. Commonly used Doppler techniques include color-flow imaging, pulsed-wave, and continuous-wave Doppler. Color-flow imaging gives general information on the direction and velocity of flow. Pulsed- and continuous-wave Doppler imaging give more precise measurements of blood velocity. The role of M-mode in the ultrasound examination has decreased as other ultrasound modalities have been developed. M-mode is still used to measure LV end-diastolic and end-systolic dimensions and permits calculation of the LV-shortening fraction, a standard estimate of LV function (SF = LV end-diastolic volume – LV systolic volume/LV end-diastolic volume). Three-dimensional echocardiography, tissue Doppler, strain, and strain rate imaging are newer modalities that provide more sophisticated assessment of systolic and diastolic function and can detect early changes in myocardial function.

A typical transthoracic echocardiogram performed by a skilled sonographer takes about 30 minutes, and patients must be still for the examination. Frequently infants and children cannot cooperate for the examination and sedation is required. Transesophageal echocardiography requires general anesthesia in infants and children and is primarily used to guide interventional procedures and surgical repair of congenital heart disease. In cases of difficult imaging windows due to patient size, air interference or when looking for evidence of vegetations on cardiac valves, transesophageal echocardiography may be necessary.

It is important to note that fetal echocardiography plays an important role in the prenatal diagnosis of congenital heart disease. A fetal echocardiogram is recommended if the fetus is considered high risk for the development of congenital heart disease or if there is suspicion for structural heart disease or fetal arrhythmias based on the obstetric fetal ultrasound. In utero management of fetal arrhythmias and postdelivery planning for the fetus with complex heart disease have resulted in improved outcomes for this challenging group of patients.

MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) of the heart is valuable for evaluation and noninvasive follow-up of many congenital heart defects. It is particularly useful in imaging the thoracic vessels, which are difficult to image by transthoracic echocardiogram. Cardiac gated imaging allows dynamic evaluation of structure and blood flow of the heart and great vessels. Cardiac MRI provides unique and precise imaging in patients with newly diagnosed or repaired aortic coarctation and defines the aortic dilation in Marfan, Turner, and Loeys-Dietz syndromes. Cardiac MRI can quantify regurgitant lesions such as pulmonary insufficiency (PI) after repair of tetralogy of Fallot (ToF) and can define ventricular function, chamber size, and wall thickness in patients with inadequate echocardiographic images or cardiomyopathies. MRI is especially useful to characterize RV size and function as this chamber is often difficult to image comprehensively by echocardiogram. Because it allows computer manipulation of images of the heart and great vessels, three-dimensional MRI is an ideal noninvasive way of obtaining accurate reconstructions of the heart. General anesthesia is often required to facilitate cardiac MRI performance in children younger than 8 years.

CARDIOPULMONARY STRESS TESTING

Cardiopulmonary stress testing provides objective measurements in children with congenital cardiac lesions to ascertain limitations, develop exercise programs, assess effects of medical or surgical therapies, and determine need for cardiac transplantation. Most children with heart disease are capable of normal activity. Bicycle ergometers or treadmills can be used in children as young as 5 years. The addition of a metabolic cart enables one to assess whether exercise impairment is secondary to cardiac limitation, pulmonary limitation, deconditioning, or lack of effort. Exercise variables include the ECG, blood pressure response to exercise, oxygen saturation, ventilation, maximal oxygen consumption, and peak workload attained. Stress testing is also employed in children with structurally normal hearts who have complaints of exercise-induced symptoms to rule out cardiac or pulmonary pathology. Significant stress ischemia or dysrhythmias warrant physical restrictions or appropriate therapy. Children with poor performance due to suboptimal conditioning benefit from a planned exercise program.

ARTERIAL BLOOD GASES & PULSE OXIMETRY

Quantitating the partial arterial oxygen pressure (PaO₂) or O₂ saturation (SaO₂) during the administration of 100% oxygen is the most useful method of distinguishing hypoxemia produced primarily by heart disease or by lung disease—the so-called hyperoxia test. In cyanotic heart disease, hypoxemia is caused by shunting of de-oxygenated blood to the systemic circulation and, thus, when compared to values obtained while breathing room air, the SaO₂ and PaO₂ increase very little when 100% oxygen is administered. However, in a patient with hypoxemia caused by lung disease, the SaO₂ and PaO₂ usually increase significantly when oxygen is administered. Table 20–11 illustrates the respective responses seen in patients during the hyperoxia test.

In 2010, the US Department of Health and Human Services (HHS) recommended newborn screening for critical congenital heart disease with pulse oximetry screening at 24–48 hours of age. Both the American Academy of Pediatrics (AAP) and American Heart Association (AHA) endorsed this recommendation in 2012.

CARDIAC CATHETERIZATION & ANGIOCARDIOGRAPHY

Cardiac catheterization is an invasive method to evaluate anatomic and physiologic conditions in congenital or acquired heart disease. Management decisions may be made based on oximetric, hemodynamic, or angiographic data obtained through a catheterization. In an increasing number of cases, intervention may be performed during a catheterization that may palliate, or even cure, a congenital heart defect without open heart surgery.

Cardiac Catheterization Data

Figure 20–3 shows oxygen saturation (in percent) and pressure (in millimeters of mercury) values obtained at cardiac catheterization from the chambers and great arteries of the heart. These values represent the normal range for a school age child.

A. Oximetry, Shunts, and Cardiac Output

Measurement of oxygen levels throughout the heart and surrounding blood vessels can provide a wealth of information about a patient’s physiology. The difference between systemic saturation (in the aorta) and mixed venous saturation (usually in the superior vena cava [SVC]) is usually inversely proportional to the overall cardiac output. Cardiac output is determined by saturation difference across a vascular bed, taking into account oxygen consumption and hemoglobin. This is known as the Fick principle. Cardiac output in a healthy heart varies directly with the body’s oxygen consumption and is inversely proportional to hemoglobin. The circulatory system of patients who are anemic usually tries to generate a higher cardiac output to maintain oxygen delivery to the cells of the body.

An increase in saturation across the right side of the heart (anywhere between SVC and pulmonary arteries) represents a left-to-right shunt. If oxygenated blood can mix with venous blood, the saturation rises—the degree of which correlates with the size of the shunt. Conversely, a fall in saturation across the left heart, between the pulmonary veins and the aorta, is abnormal. This represents the addition of deoxygenated blood to oxygenated blood—a right-to-left shunt.

A commonly referenced ratio in pediatric cardiology is the Qp:Qs. In a normal heart, systemic cardiac output (Qs) and pulmonary blood flow (Qp) are equal, or Qp:Qs = 1. If a step-up in saturation is noted across the right heart, suggesting a left-to-right shunt, pulmonary blood flow will exceed systemic blood flow. This can result, in cases of large shunts, in a Qp:Qs of as high as 3:1 or more. This level of shunt is usually poorly tolerated, but small shunts (such as 1.5:1) may be well tolerated for months or years. In cases of right-to-left shunts, Qs will exceed Qp. In these cyanotic patients, the Qp:Qs may be 0.7 or 0.8.

B. Pressures

Pressures should be determined in all chambers and major vessels entered. Systolic pressure in the RV should be equal to the systolic pressure in the pulmonary artery. Likewise, the systolic pressure in the LV should be equal to the systolic pressure of the aorta. The mean pressure in the atria should be nearly equal to (or a point or two lower than) the end-diastolic pressure of the ventricles. If a gradient in pressure exists, an obstruction is present, and the severity of the gradient is one criterion for the necessity of intervention.

For example, an LV systolic pressure in a small child of 140 mm Hg and an aortic systolic pressure of 80 mm Hg, a gradient of 60 mm Hg, would classify as severe aortic valve stenosis. Balloon aortic valvuloplasty would be indicated at the time of the catheterization.

C. Vascular Resistance

In addition to pressure and flow, resistance completes the “concept triad” of congenital heart physiology. Resistance is related to pressure and flow as described in the below equation:

The resistance across a vascular bed can be concretely calculated. Patients with congenital heart disease or pulmonary vascular disease may have elevation in pulmonary vascular resistance (PVR), which can adversely impact circulation and heart function. To calculate PVR, the pressure drop from the pulmonary arteries to the left atrium is divided by pulmonary blood flow (Qp) to obtain a value in units. For example, a patient with a mean pulmonary artery pressure (PAP) of 15 mm Hg and a left atrial pressure of 9 mm Hg, with a Qp of 3 L/min/m², has a PVR of 2 U/m².

Normal PVR is less than 3 U/m². Systemic vascular resistance normally covers a wider range, usually from 10 to 30 U/m². The ratio of pulmonary to systemic vascular resistance is usually less than 0.3. High pulmonary resistance, or a high ratio of resistance, denotes abnormal pulmonary vasculature. It often represents increased risk in patients with congenital heart disease or PH and results in higher risk of death in severely affected patients.

Cardiac catheterization can be performed to evaluate the effects of pharmaceutical therapy. An example of this use of catheterization is monitoring changes in PVR during the administration of nitric oxide or prostacyclin in a child with primary PH.

Angiography

In the past, angiography was a mainstay of the initial diagnostic methods for congenital heart disease. It is still used for diagnostic purposes in selected cases but currently is used more frequently to plan interventions or evaluate postsurgical anatomy that is poorly seen by noninvasive methods. Injection of contrast liquid via a well-positioned catheter can illuminate detailed intracardiac and intravascular anatomy more clearly than any other method. Cardiac function can be observed, and anatomic abnormalities may be easily identified. In a growing number of centers, three-dimensional reconstruction of angiograms can provide exquisite delineation of cardiac and vascular structures.

Interventional Cardiac Catheterization

Interventional cardiac catheterization procedures are performed to occlude lesions such as a PDA, atrial septal defect (ASD), or ventricular septal defect (VSD). Obstruction of heart valves can be addressed through balloon valvuloplasty. Intervention may also be performed on vascular obstruction through angioplasty or stent placement in pulmonary arteries or the aorta. Systemic and pulmonary veins can be modified in a similar fashion, unfortunately with often minimal success in the latter. Devices are now available to allow patients to undergo replacement of failing heart valves without open heart surgery, and an increasing armamentarium of devices are becoming available for treatment of other defects and abnormal vasculature.

With the progression of improved noninvasive imaging, fewer diagnostic cardiac catheterization studies are performed today. The number of interventional procedures, however, is on the rise. Although the risks of cardiac catheterization are very low for elective studies in older children (< 1%), the risk of major complications in distressed or small patients is higher. Interventional procedures, particularly in unstable babies and children, increase these risks further. Increased use of registries is currently being employed to better understand efficacy rates and risks of these procedures, with the hope of optimizing the care of infants and children in the catheterization laboratory.

At birth, two events affect the cardiovascular and pulmonary system: (1) the umbilical cord is clamped, removing the placenta from the maternal circulation and (2) breathing commences. As a result, marked changes in the circulation occur. During fetal life, the placenta offers low resistance to blood flow. In contrast, the pulmonary arterioles are markedly constricted and there is high resistance to blood flow in the lungs. Therefore, the majority of blood entering the right side of the heart travels from the right atrium into the left atrium across the foramen ovale (right-to-left shunt). In addition, most of the blood that makes its way into the RV and then pulmonary arteries will flow from the pulmonary artery into the aorta through the ductus arteriosus (right-to-left shunt). Subsequently, pulmonary blood flow accounts for only 7%–10% of the combined in utero ventricular output. At birth, pulmonary blood flow dramatically increases with the fall in PVR and pressure. The causes of prolonged high PVR include physical factors (lack of an adequate air-liquid interface or ventilation), low oxygen tension, and vasoactive mediators such as elevated endothelin peptide levels or leukotrienes. Clamping the umbilical cord produces an immediate increase in resistance to flow in the systemic circuit.

As breathing commences, the PO₂ of the small pulmonary arterioles increases, resulting in a decrease in PVR. Increased oxygen tension, rhythmic lung distention, and production of nitric oxide as well as prostacyclin play major roles in the fall in PVR at birth. The PVR falls below that of the systemic circuit, resulting in a reversal in direction of blood flow across the ductus arteriosus and marked increase in pulmonary blood flow.

Functional closure of the ductus arteriosus begins shortly after birth. The ductus arteriosus usually remains patent for 1–5 days. During the first hour after birth, a small right-to-left shunt is present (as in the fetus). However, after 1 hour, bidirectional shunting occurs, with the left-to-right direction predominating. In most cases, right-to-left shunting disappears completely by 8 hours. In patients with severe hypoxia (eg, in the syndrome of persistent PH of the newborn), PVR remains high, resulting in a continued right-to-left shunt. Although flow through the ductus arteriosus usually is gone by 5 days of life, the vessel does not close anatomically for 7–14 days.

In fetal life, the foramen ovale serves as a one-way valve shunting blood from the inferior vena cava (IVC) through the right atrium into the left atrium. At birth, because of the changes in the pulmonary and systemic vascular resistance and the increase in the quantity of blood returning from the pulmonary veins to the left atrium, the left atrial pressure rises above that of the right atrium. This functionally closes the flap of the foramen ovale, preventing flow of blood across the septum. The foramen ovale remains probe patent in 10%–15% of adults.

Persistent PH is a clinical syndrome of full-term infants. The neonate develops tachypnea, cyanosis, and PH during the first 8 hours after delivery. These infants have massive right-to-left ductal and/or foramen shunting for 3–7 days because of high PVR. Progressive hypoxia and acidosis will cause early death unless the pulmonary resistance can be lowered. Postmortem findings include increased thickness of the pulmonary arteriolar media. Increased alveolar PO₂ with hyperventilation, alkalosis, paralysis, surfactant administration, high-frequency ventilation, and cardiac inotropes can usually reverse this process. Inhaled nitric oxide selectively dilates pulmonary vasculature, produces a sustained improvement in oxygenation, and has resulted in improved outcomes.

In the normal newborn, PVR and pulmonary arterial pressure continue to fall during the first weeks of life as a result of demuscularization of the pulmonary arterioles. Adult levels of pulmonary resistance and pressure are normally achieved by 4–6 weeks of age. It is at this time typically that signs of pulmonary overcirculation associated with left-to-right shunt lesions VSD or atrioventricular septal defect [AVSD]) appear.

Heart failure (HF) is the clinical condition in which the heart fails to meet the circulatory and metabolic needs of the body. Right and left HF can result from volume or pressure overload of the respective ventricle or an intrinsic abnormality of the ventricular myocardium. Causes of RV volume overload include an ASD, pulmonary valve insufficiency, or anomalous pulmonary venous return. LV volume overload occurs with any left-to-right shunting lesion (eg, VSD, PDA), aortic valve insufficiency, or a systemic arteriovenous malformation. Causes of RV failure as a result of pressure overload include PH, valvar pulmonary stenosis, or severe branch PPS. LV pressure overload results from left heart obstructive lesions such as aortic stenosis (subvalvar, valvar, or supravalvar) or coarctation of the aorta. Abnormalities of the RV myocardium that can result in right HF include Ebstein anomaly (atrialization of the RV) and arrhythmogenic RV dysplasia (a genetic disorder where the RV myocardium is replaced by fat). Abnormalities of the LV myocardium are more common and include dilated cardiomyopathy (DCM), myocarditis, or hypertrophic cardiomyopathy (HCM). As a result of elevated left atrial pressure and impaired relaxation of the LV, left HF can lead to right HF. Other causes of HF in infants include AVSD, coronary artery anomalies, and chronic atrial tachyarrhythmias. Metabolic, mitochondrial, and neuromuscular disorders with associated cardiomyopathy present at various ages depending on the etiology. HF due to acquired conditions such as myocarditis can occur at any age. Children with HF may present with irritability, diaphoresis with feeds, fatigue, exercise intolerance, or evidence of pulmonary congestion (see Table 20–1).

Treatment of Heart Failure

The therapy of HF should be directed toward the underlying cause as well as the symptoms. Regardless of the etiology, neurohormonal activation occurs early when ventricular systolic dysfunction is present. Plasma catecholamine levels (eg, norepinephrine) increase causing tachycardia, diaphoresis, and activation of the renin-angiotensin system (which, in turn, results in peripheral vasoconstriction and salt and water retention). Although an evidence basis for treatment of pediatric HF is lacking, therapies should be aimed at improving cardiac performance by targeting the three determinants of cardiac performance: (1) preload, (2) afterload, and (3) contractility.

Inpatient Management of Heart Failure

Patients with cardiac decompensation may require hospitalization for initiation or augmentation of HF therapy. Table 20–12 demonstrates intravenous inotropic agents used to augment cardiac output and their relative effect on heart rate, systemic vascular resistance, and cardiac index. The drug used will depend in part on the cause of the HF. Of the drugs listed in Table 20–12, norepinephrine would not be utilized alone due to its mild effect on contractility and cardiac index and more profound effect of increasing systemic vascular resistance, and thus afterload.

A. Inotropic and Mechanical Support

1. Afterload reduction and systemic vasodilatation

A. MILRINONE—This phosphodiesterase-3 inhibitor potentiates calcium delivery to the myocardium, thereby improving the inotropic state of the heart. Milrinone is an inodilator with systemic and pulmonary vasodilatory effects, in addition to a dose-dependent increase in cardiac contractility. Thus, milrinone is an effective agent in both right and left HF. Milrinone also reduces the incidence of low cardiac output syndrome following open-heart surgery. The usual intravenous infusion dosage range is 0.25–0.75 mcg/kg/min.

B. NITRATES—Nitroprusside is a nitric oxide donor that induces arterial and venous vasodilatation. Venous vasodilatation allows for increased capacitance, reduction of venous preload, and reduction of right atrial pressure. Arterial vasodilatation reduces LV afterload but can also cause hypotension. A common adverse effect is reflex tachycardia. Nitroglycerin exerts similar effects with increased venous selectivity and is also used to improve coronary blood flow in settings of myocardial infarction or coronary underperfusion following congenital heart surgery. The usual intravenous infusion dosages for nitroprusside and nitroglycerin range are 0.25–3 mcg/kg/min.

2. Enhancement of contractility

A. EPINEPHRINE—Also known as adrenaline, this catecholamine is a potent stimulator of α₁-, β₁-, and β₂-adrenergic receptors resulting in bronchodilatation, cardiac stimulation, and systemic vasodilatation. Epinephrine demonstrates dose-dependent effects on the vasculature with vasodilatation at low doses via β₂ receptors and vasoconstriction at high doses via α₁-receptor activation. The β₁ effects induce both increased inotropy and chronotropy (heart rate). The usual intravenous infusion dosage range is 0.05–2 mcg/kg/min. Other non-HF indications for epinephrine include anaphylaxis, bronchoconstriction, shock, and bradycardia or pulseless cardiac arrest.

B. DOPAMINE—This naturally occurring catecholamine increases myocardial contractility primarily via stimulation of adrenergic and dopaminergic receptors. Renal dopamine receptor activation improves renal perfusion. The usual dose range for HF is 2–10 mcg/kg/min.

C. DOBUTAMINE—This synthetic catecholamine increases myocardial contractility secondary to cardiospecific β-adrenergic activation and produces little peripheral vasoconstriction. Dobutamine does not usually cause marked tachycardia, which is a distinct advantage. However, the drug does not selectively improve renal perfusion as does dopamine. The usual intravenous infusion dose range is 2–10 mcg/kg/min.

3. Mechanical circulatory support

Mechanical support is indicated in children with severe, refractory myocardial failure secondary to cardiomyopathy, myocarditis, or following cardiac surgery. Mechanical support is used for a limited time while cardiac function improves or as a bridge to cardiac transplantation.

A. EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO)—ECMO is a temporary means of providing gas exchange and hemodynamic support to patients with cardiac or pulmonary failure refractory to conventional therapy. Blood is withdrawn from the patient by a pump via a cannula positioned at the SVC or right atrium and passes through a membrane oxygenator (to exchange both O₂ and CO₂). This oxygenated blood is then delivered back to the patient through a cannula in the aorta (via the common carotid artery). Systemic anticoagulation is needed to prevent clot formation in the circuit. The patient is monitored closely while awaiting improvement in cardiac function. Risks are significant and include severe bleeding, infection, end organ injury (kidneys, in particular), stroke, and patient or circuit thrombosis.

B. VENTRICULAR ASSIST DEVICES—Use of ventricular assist devices is increasing in children as device development has progressed. These devices allow for less invasive hemodynamic support than ECMO. In this case, a cannula is usually positioned in the apex of the ventricle and blood is withdrawn from the ventricle using a battery-operated pump. Blood is then returned to the patient through a separate cannula positioned in the aorta or pulmonary artery, depending on the ventricle being supported. One or both ventricles can be supported, if necessary. Ventricular assist carries lower risk of circuit thrombosis than ECMO, but the risk of infection, patient thrombosis, and bleeding complications remains.

Outpatient Management of Heart Failure

A. Medications

1. Afterload-reducing agents

Oral afterload-reducing agents improve cardiac output by decreasing systemic vascular resistance. Angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril, and lisinopril) are first-line therapy in children with HF requiring long-term treatment. These agents block angiotensin II–mediated systemic vasoconstriction and are particularly useful in children with reduced LV myocardial function (eg, myocarditis or DCMs).

2. Beta-Blockade

Although clearly beneficial in adults with HF, β-blocker therapy in children with HF did not demonstrate any significant improvement compared to placebo. However, β-blockers may still be useful adjunctive therapy in some children who are already taking ACE inhibitors and have refractory HF requiring additional afterload reduction. The neurohumoral response to HF includes excessive circulating catecholamines due to activation of the sympathetic nervous system. Although beneficial acutely, this compensatory response over time produces myocardial fibrosis, myocyte hypertrophy, and myocyte apoptosis that contribute to the progression of HF. β-Blockers (eg, carvedilol and metoprolol) antagonize this sympathetic activation and may offset these deleterious effects. Side effects of β-blockers include bradycardia, hypotension, and worsening HF in some patients.

3. Diuretics

Diuretic therapy is often necessary in HF to maintain the euvolemic state and control symptoms related to pulmonary or hepatic congestion caused by sodium and water retention as a consequence of renin-angiotensin system activation.

A. FUROSEMIDE—This loop diuretic inhibits sodium-chloride-potassium cotransport and reabsorption at the loop of Henle. When used chronically, loop diuretics induce potassium and chloride excretion, producing hypochloremic metabolic alkalosis and hypokalemia for which electrolytes should be monitored.

B. THIAZIDES—Thiazides inhibit sodium chloride reabsorption at the distal convoluted tubule and are used to complement furosemide in severe cases of HF.

C. SPIRONOLACTONE—Spironolactone is an aldosterone inhibitor used frequently in conjunction with other diuretics for its potassium sparing effect (often helps avoid the need for potassium supplementation). Though not proven in children, the aldosterone inhibitory effect of spironolactone has benefit in adults with HF, separate from its diuretic effect, as aldosterone is associated with the development of fibrosis, sodium retention, and vascular dysfunction.

4. Digitalis

Digitalis is a cardiac glycoside with a positive inotropic effect on the heart and an associated decrease in systemic vascular resistance. The preparation of digitalis used in clinical practice is digoxin. Large studies in adult patients with HF have not demonstrated decreased mortality of HF with digoxin use, but treatment is associated with reduced hospitalization rates for HF exacerbations. No controlled studies exist in children,

A. DIGITALIS TOXICITY—Any dysrhythmia that occurs during digoxin therapy should be attributed to the drug until proven otherwise. Ventricular dysrhythmia and first-, second-, or third-degree AV block are characteristic of digoxin toxicity. A trough level should be obtained if digoxin toxicity is suspected.

B. DIGITALIS POISONING—This acute emergency must be treated without delay. Digoxin poisoning most commonly occurs in toddlers who have taken their parents’ or grandparents’ medications. The child’s stomach should be emptied immediately by gastric lavage, and activated charcoal may be indicated in severe poisonings. Toxicity may induce high grade heart block, for which atropine or temporary ventricular pacing may be needed. Antiarrhythmic agents may also be needed. Digoxin immune Fab can be used to reverse potentially life-threatening intoxication.

Environmental factors such as maternal diabetes, alcohol consumption, progesterone use, viral infection, and other maternal teratogen exposure are associated with an increased incidence of cardiac malformations. However, the importance of genetics as a cause of congenital heart disease is becoming more evident as advances in the field occur. Microdeletion in the long arm of chromosome 22 (22q11) is associated with DiGeorge syndrome. These children often have conotruncal abnormalities such as truncus arteriosus, ToF, double-outlet RV, or interrupted aortic arch. Alagille, Noonan, Holt-Oram, and Williams syndromes and the trisomies 13, 18, and 21 are all commonly associated with congenital heart lesions. Understanding these associations as well as further targeted study investigating the genetic basis of other cardiac lesions will offer opportunities for early diagnosis, gene therapy, and recurrence risk counseling for families.

DEFECTS IN SEPTATION

1. Atrial Septal Defect

General Considerations

Atrial septal defect (ASD) is an opening in the atrial septum permitting the shunting of blood between the atria. There are three major types: ostium secundum, ostium primum, and sinus venosus. Ostium secundum is the most common type and represents an embryologic deficiency in the septum secundum or too large of a central hole in the septum primum. Ostium primum defect is associated with AVSDs. The sinus venosus defect is frequently associated with abnormal pulmonary venous return, as the location of the sinus venosus is intimately related to the right upper pulmonary vein.

Ostium secundum ASD occurs in 10% of patients with congenital heart disease and is two times more common in females than in males. The defect is most often sporadic but may be familial or have a genetic basis (Holt-Oram syndrome). After the third decade, atrial arrhythmias or pulmonary vascular disease may develop. Irreversible PH resulting in cyanosis as atrial level shunting becomes right-to-left and ultimately right HF can occur and is a life-limiting process (Eisenmenger syndrome).

Clinical Findings

A. Symptoms and Signs

Most infants and children with an ASD have no cardiovascular symptoms. Older children and adults can present with exercise intolerance, easy fatigability, or, rarely, HF. The direction of flow across the ASD is determined by the compliance of the ventricles. Because the RV is normally more compliant, shunting across the ASD is left-to-right as blood follows the path of least resistance. Therefore, cyanosis does not occur unless RV dysfunction occurs, usually as a result of PH, leading to reversal of the shunt across the defect.

Peripheral pulses are normal and equal. The heart is usually hyperactive, with an RV heave felt best at the mid to lower left sternal border. S₂ at the pulmonary area is widely split and often fixed. In the absence of associated PH, the pulmonary component is normal in intensity. A grade I–III/VI ejection-type systolic murmur is heard best at the left sternal border in the second intercostal space. This murmur is caused by increased flow across the pulmonic valve, not flow across the ASD. A mid-diastolic murmur is often heard in the fourth intercostal space at the left sternal border. This murmur is caused by increased flow across the tricuspid valve during diastole. The presence of this murmur suggests high flow with a pulmonary-to-systemic blood flow ratio greater than 2:1.

B. Imaging

Radiographs may show cardiac enlargement. The main pulmonary artery may be dilated and pulmonary vascular markings increased in large defects owing to the increased pulmonary blood flow.

C. Electrocardiography

The usual ECG shows right-axis deviation. In the right precordial leads, an rsR’ pattern is usually present. A mutation in the cardiac homeobox gene (NKX2-5) is associated with an ASD, and AV block would be seen on the ECG.

D. Echocardiography

Echocardiography shows a dilated right atrium and RV. Direct visualization of the exact anatomic location of the ASD by two-dimensional echocardiography, and demonstration of a left-to-right shunt through the defect by color-flow Doppler, confirms the diagnosis and has eliminated the need for cardiac catheterization prior to surgical or catheter closure of the defect. Assessment of all pulmonary veins should be made to rule out associated anomalous pulmonary venous return.

E. Cardiac Catheterization

Although cardiac catheterization is rarely needed for diagnostic purposes, transcatheter closure of an ostium secundum ASD is now the preferred method of treatment.

If a catheterization is performed, oximetry shows a significant step-up in oxygen saturation from the SVC to the right atrium. The PAP and PVR are usually normal. The Qp:Qs may vary from 1.5:1 to 4:1.

Treatment

Surgical or catheterization closure is generally recommended for symptomatic children with a large atrial level defect and associated right heart dilation. In the asymptomatic child with a large hemodynamically significant defect, closure is performed electively at age 1–3 years. Most defects are amenable to nonoperative device closure during cardiac catheterization, but the defect must have adequate tissue rims on all sides on which to anchor the device. The mortality for surgical closure is less than 1%. When closure is performed by age 3 years, late complications of RV dysfunction and dysrhythmias are avoided.

Course & Prognosis

Patients usually tolerate an ASD well in the first two decades of life, and the defect often goes unnoticed until middle or late adulthood. PH and reversal of the shunt are rare late complications. Infective endocarditis (IE) is uncommon. Spontaneous closure occurs, most frequently in children with a defect less than 4 mm in diameter; therefore, outpatient follow-up is recommended. Exercise tolerance and oxygen consumption in surgically corrected children are generally normal, and restriction of physical activity is unnecessary.

2. Ventricular Septal Defect

General Considerations

VSD is the most common congenital heart malformation, accounting for about 30% of all congenital heart disease. Defects in the ventricular septum occur both in the membranous portion of the septum (most common) and the muscular portion. VSDs follow one of four courses:

A. Small, Hemodynamically Insignificant Ventricular Septal Defects

Between 80% and 85% of VSDs are small (< 3 mm in diameter) at birth and will close spontaneously. In general, small defects in the muscular interventricular septum will close sooner than those in the membranous septum. In most cases, a small VSD never requires surgical closure. Fifty percent of small VSDs will close by age 2 years, and 90% by age 6 years, with most of the remaining closing during the school years.

B. Moderate-Sized Ventricular Septal Defects

Asymptomatic patients with moderate-sized VSDs (3–5 mm in diameter) account for 3%–5% of children with VSDs. In general, these children do not have clear indicators for surgical closure. Historically, in those who had cardiac catheterization, the ratio of pulmonary to systemic blood flow is usually less than 2:1, and serial cardiac catheterizations demonstrate that the shunts get progressively smaller. If the patient is asymptomatic and without evidence of PH, these defects can be followed serially as some close spontaneously over time.

C. Large Ventricular Septal Defects with Normal Pulmonary Vascular Resistance

These defects are usually 6–10 mm in diameter. Unless they become markedly smaller within a few months after birth, they often require surgery. The timing of surgery depends on the clinical situation. Many infants with large VSDs and normal PVR develop symptoms of failure to thrive, tachypnea, diaphoresis with feeds by age 3–6 months, and require correction at that time. Surgery before age 2 years in patients with large VSDs essentially eliminates the risk of pulmonary vascular disease.

D. Large Ventricular Septal Defects With Pulmonary Vascular Obstructive Disease

The direction of flow across a VSD is determined by the resistance in the systemic and pulmonary vasculature, explaining why flow is usually left-to-right. In large VSDs, ventricular pressures are equalized, resulting in increased PAP. In addition, shear stress caused by increased volume in the pulmonary circuit causes increased resistance over time. The vast majority of patients with inoperable PH develop the condition progressively. The combined data of the multicenter National History Study indicate that almost all cases of irreversible PH can be prevented by surgical repair of a large VSD before age 2 years.

Clinical Findings

A. Symptoms and Signs

Patients with small or moderate left-to-right shunts usually have no cardiovascular symptoms. Patients with large left-to-right shunts are usually ill early in infancy. These infants have frequent respiratory infections and gain weight slowly. Dyspnea, diaphoresis, and fatigue are common. These symptoms can develop as early as 1–6 months of age. Older children may experience exercise intolerance. Over time, in children and adolescents with persistent large left-to-right shunt, the pulmonary vascular bed undergoes structural changes, leading to increased PVR and reversal of the shunt from left-to-right to right-to-left (Eisenmenger syndrome). Cyanosis will then be present.

1. Small left-to-right shunt

No lifts, heaves, or thrills are present. The first sound at the apex is normal, and the second sound at the pulmonary area is split physiologically. A grade II–IV/VI, medium- to high-pitched, harsh pansystolic murmur is heard best at the left sternal border in the third and fourth intercostal spaces. The murmur radiates over the entire precordium. No diastolic murmurs are heard.

2. Moderate left-to-right shunt

Slight prominence of the precordium with moderate LV heave is evident. A systolic thrill may be palpable at the lower left sternal border between the third and fourth intercostal spaces. The second sound at the pulmonary area is most often split but may be single. A grade III–IV/VI, harsh pansystolic murmur is heard best at the lower left sternal border in the fourth intercostal space. A mitral diastolic flow murmur indicates that pulmonary blood flow and subsequently the pulmonary venous return are significantly increased by the large shunt.

3. Large ventricular septal defects with pulmonary hypertension

The precordium is prominent, and the sternum bulges. Both LV and RV heaves are palpable. S₂ is palpable in the pulmonary area. A thrill may be present at the lower left sternal border. S₂ is usually single or narrowly split, with accentuation of the pulmonary component. The murmur ranges from grade I to IV/VI and is usually harsh and pansystolic. Occasionally, when the defect is large or ventricular pressures approach equivalency, a murmur is difficult to hear. A diastolic flow murmur may be heard, depending on the size of the shunt.

B. Imaging

In patients with small shunts, the chest radiograph may be normal. Patients with large shunts have significant cardiac enlargement involving both the LV and RV and the left atrium. The main pulmonary artery segment may be dilated. The pulmonary vascular markings are increased.

C. Electrocardiography

The ECG is normal in small left-to-right shunts. Left ventricular hypertrophy (LVH) usually occurs in patients with large left-to-right shunts and normal PVR. Combined ventricular enlargement occurs in patients with PH caused by increased flow, increased resistance, or both. Pure right ventricular hypertrophy (RVH) occurs in patients with PH secondary to pulmonary vascular obstruction induced by long-standing left-to-right shunt (Eisenmenger syndrome).

D. Echocardiography

Two-dimensional echocardiography can reveal the size of a VSD and identify its anatomic location. Multiple defects can be detected by combining two-dimensional and color-flow imaging. Doppler can further evaluate the VSD by estimating the pressure difference between the LV and RV. A pressure difference greater than 50 mm Hg in the LV compared to the RV confirms the absence of severe PH.

E. Cardiac Catheterization and Angiocardiography

The ability to describe the VSD anatomy and estimate the PAPs on the basis of the gradient across the VSD allows for the vast majority of isolated defects to be repaired without cardiac catheterization and angiocardiography. Catheterization is indicated in those patients with increased PVR. Angiocardiographic examination defines the number, size, and location of the defects.

Treatment

A. Medical Management

Patients who develop symptoms can be managed with anticongestive treatment, particularly diuretics and systemic afterload reduction, prior to surgery or if it is expected that the defect will close over time.

B. Surgical Treatment

Patients with cardiomegaly, poor growth, poor exercise tolerance, or other clinical abnormalities who have a significant shunt (> 2:1) typically undergo surgical repair at age 3–6 months. A synthetic or pericardial patch is used for primary closure. In most centers, these children have surgery before age 1 year. As a result, Eisenmenger syndrome has been virtually eliminated. The surgical mortality rate for VSD closure is below 2%.

Transcatheter closure of muscular VSDs is also a possibility. Perimembranous VSDs have also been closed in children during catheterization, but a high incidence of complete heart block after placement of the occluding device has slowed the acceptance of this approach.

Course & Prognosis

Significant late dysrhythmias are uncommon. Functional exercise capacity and oxygen consumption are usually normal, and physical restrictions are unnecessary. Adults with corrected defects have normal quality of life.

3. Atrioventricular Septal Defect

General Considerations

Atrioventricular septal defect (AVSD) results from incomplete fusion of the embryonic endocardial cushions. The endocardial cushions help to form the “crux” of the heart, which includes the lower portion of the atrial septum, the membranous portion of the ventricular septum, and the septal leaflets of the tricuspid and mitral valves. AVSD accounts for about 4% of all congenital heart disease. Sixty percent of children with Down syndrome have congenital heart disease, and of these, 35%–40% have an AVSD.

AVSDs are defined as partial or complete. The physiology of the defect is determined by the location of the AV valves. If the valves are located in the midportion of the defect (complete AVSD), both atrial and ventricular components of the septal defect are present and the left- and right-sided AV valves share a common ring or orifice. In the partial form, there is a low insertion of the AV valves, resulting in a primum ASD without a ventricular defect component. In partial AVSD, there are two separate AV valve orifices and usually a cleft in the left-sided valve.

Partial AVSD behaves like an isolated ASD with variable amounts of regurgitation through the cleft in the left AV valve. The complete form causes large left-to-right shunts at both the ventricular and atrial levels with variable degrees of AV valve regurgitation. If there is increased PVR, the shunts may be bidirectional. Bidirectional shunting is more common in Down syndrome or in older children who have not undergone repair.

Clinical Findings

A. Symptoms and Signs

The partial form may produce symptoms similar to ostium secundum ASD. Patients with complete AVSD usually have symptoms such as failure to thrive, tachypnea, diaphoresis with feeding, or recurrent bouts of pneumonia.

In the neonate with the complete form, the murmur may be inaudible due to relatively equal systemic and pulmonary vascular resistance (PVR). After 4–6 weeks, as PVR drops, a nonspecific systolic murmur develops. The murmur is usually not as harsh as that of an isolated VSD. There is both right- and left-sided cardiac enlargement. S₂ is loud, and a pronounced diastolic flow murmur may be heard at the apex and the lower left sternal border.

If severe pulmonary vascular obstructive disease is present, there is usually dominant RV enlargement. S₂ is palpable at the pulmonary area, and no thrill is felt. A nonspecific short systolic murmur is heard at the lower left sternal border. No diastolic flow murmurs are heard. If a right-to-left shunt is present, cyanosis will be evident.

B. Imaging

Cardiac enlargement is always present in the complete form and pulmonary vascular markings are increased. Often, only the right heart size may be increased in the partial form, although a severe mitral valve cleft can rarely lead to left heart enlargement as well.

C. Electrocardiography

In all forms of AVSD, there is extreme left-axis deviation with a counterclockwise loop in the frontal plane. The ECG is an important diagnostic tool. Only 5% of isolated VSDs have this ECG abnormality. First-degree heart block occurs in over 50% of patients. Right, left, or combined ventricular hypertrophy is present depending on the particular defect and the presence or absence of PH.

D. Echocardiography

Echocardiography is the diagnostic test of choice. The anatomy can be well visualized by two-dimensional echocardiography. Both AV valves are at the same level, compared with the normal heart in which the tricuspid valve is more apically positioned. The size of the atrial and ventricular components of the defect can be measured. AV valve regurgitation can be detected. The LV outflow tract is elongated (gooseneck appearance), which produces systemic outflow obstruction in some patients.

E. Cardiac Catheterization and Angiocardiography

Cardiac catheterization is not routinely used to evaluate AVSD but may be used to assess PAPs and resistance in the older infant with Down syndrome, as this patient group is predisposed to early-onset PH. Increased oxygen saturation in the RV or the right atrium identifies the level of the shunt. Angiocardiography reveals the characteristic gooseneck deformity of the LV outflow tract in the complete form.

Treatment

Spontaneous closure of this type of defect does not occur, and therefore surgery is required. In the partial form, surgery carries a low mortality rate (1%–2%), but patients require follow-up because of late-occurring LV outflow tract obstruction and mitral valve dysfunction. The complete form carries a higher mortality rate. Complete correction in the first year of life, prior to the onset of irreversible PH, is obligatory.

PATENT (PERSISTENT) DUCTUS ARTERIOSUS

General Considerations

Patent ductus arteriosus (PDA) is the persistence of the normal fetal vessel joining the pulmonary artery to the aorta. It closes spontaneously in normal-term infants at 1–5 days of age. PDA accounts for 10% of all congenital heart disease. The incidence of PDA is higher in infants born at altitudes over 10,000 ft. It is twice as common in females as in males. The frequency of PDA in preterm infants weighing less than 1500 g ranges from 20% to 60%. The defect may occur as an isolated abnormality or with associated lesions, commonly coarctation of the aorta and VSD. Patency of the ductus arteriosus may be necessary in some patients with complex forms of congenital heart disease (eg, hypoplastic left heart syndrome [HLHS], pulmonary atresia [PA]). Prostaglandin E₂ (PGE₂) is a product of arachidonic acid metabolism and continuous intravenous infusion maintains ductal patency.

Clinical Findings

A. Symptoms and Signs

The clinical findings and course depend on the size of the shunt and the degree of PH.

1. Moderate to large patent ductus arteriosus

Pulses are bounding, and pulse pressure is widened due to diastolic runoff through the ductus. S₁ is normal and S₂ is usually narrowly split. In large shunts, S₂ may have a paradoxical split (eg, S₂ narrows on inspiration and widens on expiration). Paradoxical splitting is caused by volume overload of the LV and prolonged ejection of blood from this chamber.

The murmur is characteristic. It is a rough machinery murmur maximal at the second left intercostal space. It begins shortly after S₁, rises to a peak at S₂, and passes through the S₂ into diastole, where it becomes a decrescendo murmur and fades before the S₁. The murmur tends to radiate well to the anterior lung fields but relatively poorly to the posterior lung fields. A diastolic flow murmur is often heard at the apex.

2. Patent ductus arteriosus with increased pulmonary vascular resistance

Flow across the ductus is diminished. S₂ is single and accentuated, and no significant heart murmur is present. The pulses are normal rather than bounding.

B. Imaging

In an isolated PDA, the appearance of the chest radiograph depends on the size of the shunt. If the shunt is small, the heart is not enlarged. If the shunt is large, both left atrial and LV enlargement may be seen. The aorta and the main pulmonary artery segment may also be prominent.

C. Electrocardiography

The ECG may be normal or may show LVH, depending on the size of the shunt. In patients with PH caused by increased blood flow, biventricular hypertrophy usually occurs. In pulmonary vascular obstructive disease, pure RVH occurs.

D. Echocardiography

Echocardiography provides direct visualization of the ductus and confirms the direction and degree of shunting. High-velocity left-to-right flow argues against abnormally elevated PVR, and as PVR drops during the neonatal period, higher velocity left-to-right shunting is usually seen. If suprasystemic PVR is present, flow across the ductus will be seen from right to left. Associated cardiac lesions and ductal-dependent pulmonary or systemic blood flow must be recognized by echocardiography, as closure of a PDA in this setting would be contraindicated.

E. Cardiac Catheterization and Angiocardiography

PDA closure in the catheterization laboratory with a vascular plug or coils is now routine in all but the smallest of neonates and infants.

Treatment

Surgical closure is indicated when the PDA is large and the patient is small. Caution must be given to closing a PDA in patients with pulmonary vascular obstructive disease and right-to-left shunting across the ductus as this could result in RV failure. Patients with large left-to-right shunts require repair by age 1 year to prevent the development of progressive pulmonary vascular obstructive disease. Symptomatic PDA with normal PAP can be safely coil or device-occluded in the catheterization laboratory, ideally after the child has reached 5 kg.

Patients with nonreactive pulmonary vascular obstruction, PVR greater than 10 Wood units (normal, < 3), and a ratio of pulmonary to systemic resistance greater than 0.7 (normal, < 0.3) despite vasodilator therapy (eg, nitric oxide) should not undergo PDA closure. These patients are made worse by PDA closure because the flow through the ductus allows preserved RV function and maintains cardiac output to the systemic circulation. These patients can be managed with pulmonary vasodilator therapy but eventually may require heart-lung transplant in severe cases.

Presence of a symptomatic PDA is common in preterm infants. Indomethacin, a prostaglandin synthesis inhibitor, is often used to close the PDA in premature infants. Indomethacin does not close the PDA of full-term infants or children. The success of indomethacin therapy is as high as 80%–90% in premature infants with a birth weight greater than 1200 g, but it is less successful in smaller infants. Indomethacin (0.1–0.3 mg/kg orally every 8–24 hours or 0.1–0.3 mg/kg parenterally every 12 hours) can be used if there is adequate renal, hematologic, and hepatic function. Because indomethacin may impair renal function, urine output, BUN, and creatinine should be monitored during therapy. If indomethacin is not effective and the ductus remains hemodynamically significant, surgical ligation should be performed. If the ductus partially closes so that the shunt is no longer hemodynamically significant, a second course of indomethacin may be tried.

Course & Prognosis

Patients with an isolated PDA and small to moderate shunts usually do well without surgery. However, in the third or fourth decade of life, symptoms of easy fatigability, dyspnea on exertion, and exercise intolerance appear in those patients who develop PH and/or HF. Percutaneous closure can be done later in life if there has not been development of severe pulmonary vascular disease. For those with severe and irreversible PH prognosis is not good and heart-lung transplant may be needed.

Spontaneous closure of a PDA may occur up to age 1 year, especially in preterm infants. After age 1 year, spontaneous closure is rare. Because endocarditis is a potential complication, some cardiologists recommend closure if the defect persists beyond age 1 year, even if it is small. Most of these patients undergo percutaneous occlusion as opposed to surgical ligation.

RIGHT-SIDED OBSTRUCTIVE LESIONS

1. Pulmonary Valve Stenosis

General Considerations

Pulmonic valve stenosis accounts for 10% of all congenital heart disease. The pulmonary valve annulus is usually small with moderate to marked poststenotic dilation of the main pulmonary artery. Obstruction to blood flow across the pulmonary valve causes an increase in RV pressure. Pressures greater than systemic are potentially life threatening and are associated with critical obstruction. Because of the increased RV strain, severe RVH and eventual RV failure can occur.

When obstruction is severe and the ventricular septum is intact, a right-to-left shunt will often occur at the atrial level through a patent foramen ovale (PFO). In neonates with severe obstruction and minimal antegrade pulmonary blood flow (critical PS), left-to-right flow through the ductus is essential, making prostaglandin a necessary intervention at the time of birth. These infants are cyanotic at presentation.

Clinical Findings

A. Symptoms and Signs

Patients with mild or even moderate valvular pulmonary stenosis are acyanotic and asymptomatic. Patients with severe valvular obstruction may develop cyanosis early. Patients with mild to moderate obstruction are usually well developed and well nourished. They are not prone to pulmonary infections. The pulses are normal. The precordium may be prominent, often with palpable RV heave. A systolic thrill is often present in the pulmonary area. In patients with mild to moderate stenosis, a prominent ejection click of pulmonary origin is heard at the third left intercostal space. The click varies with respiration, being more prominent during expiration than inspiration. In severe stenosis, the click tends to merge with S₁. S₂ varies with the degree of stenosis. In mild pulmonic stenosis, S₂ is normal. In moderate pulmonic stenosis, S₂ is more widely split and the pulmonary component is softer. In severe pulmonary stenosis, S₂ is single because the pulmonary component cannot be heard. A rough systolic ejection murmur is best heard at the second left interspace. It radiates well to the back. With severe pulmonary valve obstruction, the murmur is usually short. No diastolic murmurs are audible.

B. Imaging

The heart size is normal. Poststenotic dilation of the main pulmonary artery and the left pulmonary artery often occurs.

C. Electrocardiography

The ECG is usually normal with mild obstruction. In severe obstruction, RV hypertrophy with an RV strain pattern (deep inversion of the T wave) occurs in the right precordial leads (V_3R, V₁, V₂). Right atrial enlargement may be present. Right-axis deviation occurs in moderate to severe stenosis.

D. Echocardiography

The diagnosis often is made by physical examination, but the echocardiogram confirms the diagnosis, defines the anatomy, and can identify any associated lesions. The pulmonary valve has thickened leaflets with reduced valve leaflet excursion. The transvalvular pressure gradient can be estimated accurately by Doppler, which provides an estimate of RV pressure and can assist in determining the appropriate time to intervene.

E. Cardiac Catheterization and Angiocardiography

Catheterization is reserved for therapeutic balloon valvuloplasty. In severe cases with associated RV dysfunction, a right-to-left shunt at the atrial level is indicated by a lower left atrial saturation than pulmonary vein saturation. PAP is normal. The gradient across the pulmonary valve varies from 10 to 200 mm Hg. In severe cases, the right atrial pressure is elevated, with a predominant “a” wave. Angiocardiography in the RV shows a thick pulmonary valve with a narrow opening producing a jet of contrast into the pulmonary artery. Infundibular (RV outflow tract) hypertrophy may be present and may contribute to obstruction to pulmonary blood flow.

Treatment

Treatment of pulmonic stenosis is recommended for children with RV systolic pressure greater than two-thirds of systemic pressure. Immediate correction is indicated for patients with systemic or suprasystemic RV pressure. Percutaneous balloon valvuloplasty is the procedure of choice. It is as effective as surgery in relieving obstruction and causes less valve insufficiency. Surgery is needed to treat pulmonic valve stenosis when balloon pulmonic valvuloplasty is unsuccessful.

Course & Prognosis

Patients with mild pulmonary stenosis live normal lives. Even those with moderate stenosis are rarely symptomatic. Those with severe valvular obstruction may develop cyanosis in infancy as described earlier.

After balloon pulmonary valvuloplasty or surgery, most patients have good maximum exercise capacity unless they have significant PI. Limitation of physical activity is unwarranted. The quality of life of adults with successfully treated pulmonary stenosis and minimal PI is normal. Patients with PI, a frequent side effect of intervention, may be significantly limited in exercise performance. Severe PI leads to progressive RV dilation and dysfunction, which may precipitate ventricular arrhythmias or right HF in adulthood. Patients with severe PI may benefit from replacement of the pulmonic valve.

2. Subvalvular Pulmonary Stenosis

Isolated infundibular (subvalvular) pulmonary stenosis is rare. More commonly it is found in combination with other lesions, such as in ToF. Infundibular hypertrophy that is associated with a small perimembranous VSD may lead to a “double-chambered RV” characterized by obstruction between the inflow and outflow portion of the RV. One should suspect such an abnormality if there is a prominent precordial thrill, no audible pulmonary ejection click, and a murmur maximal in the third and fourth inter-costal spaces rather than in the second intercostal space. The clinical picture is otherwise identical to that of pulmonic valve stenosis. Intervention, if indicated, is always surgical because this condition does not improve with balloon catheter dilation.

3. Supravalvular Pulmonary Stenosis

Supravalvular pulmonary stenosis is a relatively rare condition defined by narrowing of the main pulmonary artery. The clinical picture may be identical to valvular pulmonary stenosis, although the murmur is maximal in the first inter-costal space at the left sternal border and in the suprasternal notch. No ejection click is audible, as the valve itself is not involved. The murmur radiates toward the neck and over the lung fields. Children with Williams syndrome can have supravalvular and PPS as well as supravalvular aortic stenosis.

4. Peripheral (Branch) Pulmonary Artery Stenosis

In PPS, there are multiple narrowings of the branches of the pulmonary arteries, sometimes extending into the vessels in the periphery of the lungs. Systolic murmurs may be heard over both lung fields, anteriorly and posteriorly, radiating to the axilla. Mild, nonpathologic pulmonary branch stenosis produces a murmur in infancy that resolves by 6 months of age. Williams syndrome, Alagille syndrome, and congenital rubella are commonly associated with severe forms of peripheral PAS. Surgery is often unsuccessful, as areas of stenoses near and beyond the hilum of the lungs are not accessible to the surgeons. Transcatheter balloon angioplasty and even stent placement are used to treat this condition, with moderate success. In some instances, the stenoses improve spontaneously with age.

5. Ebstein Malformation of the Tricuspid Valve

In Ebstein malformation of the tricuspid valve, the septal leaflet of the tricuspid valve is displaced toward the apex of the heart and is attached to the endocardium of the RV rather than at the tricuspid annulus. As a result, a large portion of the RV functions physiologically as part of the right atrium. This “atrialized” portion of the RV is thin-walled and does not contribute to RV output. The portion of the ventricle below the displaced tricuspid valve is diminished in volume and represents the functioning RV.

Clinical Findings

A. Symptoms and Signs

The clinical picture of Ebstein malformation varies with the degree of displacement of the tricuspid valve. In the most extreme form, the septal leaflet is markedly displaced into the RV outflow tract, causing obstruction of antegrade flow into the pulmonary artery, and there is very little functioning RV as the majority of the ventricle is “atrialized.” The degree of tricuspid insufficiency may be so severe that forward (antegrade) flow out the RV outflow tract is further diminished leading to a right-to-left atrial level shunt and cyanosis. At the opposite extreme when antegrade pulmonary blood flow is adequate, symptoms may not develop until adulthood when tachyarrhythmias associated with right atrial dilation or reentrant electrical pathways occur. These older patients typically have less displacement of the septal leaflet of the tricuspid valve and therefore more functional RV tissue.

B. Imaging

The chest radiograph shows cardiomegaly with prominence of the right heart border. The extent of cardiomegaly depends on the degree of tricuspid valve insufficiency and the presence and size of the atrial level shunt. Massive cardiomegaly with a “wall-to-wall heart” (the heart shadow extends across the entire chest cavity from right to left) occurs with severe tricuspid valve displacement and/or a restrictive atrial level defect.

C. Electrocardiography

ECG may be normal but usually shows right atrial enlargement and RBBB. There is an association between Ebstein anomaly and Wolff-Parkinson-White (WPW) syndrome, in which case a delta wave is present (short PR with a slurred upstroke of the QRS).

D. Echocardiography

Echocardiography is necessary to confirm the diagnosis and may aid in predicting outcome. Degree of tricuspid valve displacement, size of the right atrium, and presence of associated atrial level shunt all affect outcome.

Course & Prognosis

In cyanotic neonates, PGE₂ is used to maintain pulmonary blood flow via the ductus arteriosus until PVR decreases, facilitating antegrade pulmonary artery flow. If the neonate remains significantly cyanotic, surgical intervention is required.

The type of surgical repair varies and depends on the severity of the disease. For example, in order to decrease the amount of tricuspid regurgitation surgery may involve atrial plication and tricuspid valve repair. The success of the procedure is highly variable. Late arrhythmias are common due to the preexisting atrial dilation. If a significant Ebstein malformation is not treated, atrial tachyarrhythmias frequently begin during adolescence and the enlarged atrialized RV could impede LV function. Postoperative exercise tolerance improves but remains lower than age-related norms.

LEFT-SIDED LESIONS

1. Coarctation of the Aorta

General Considerations

Coarctation of the aorta is a narrowing in the aortic arch, usually in the proximal descending aorta at the insertion of the ductus arteriosus, near the takeoff of the left subclavian artery (which is usually proximal to the obstruction). Coarctation accounts for 7% of all congenital heart disease and has a male predominance (1.5:1); many affected females have Turner syndrome (45, XO). Coarctation is associated with bicuspid aortic valve in up to 85% of cases and intracerebral (berry) aneurysms in 10% of cases.

Clinical Findings

A. Symptoms and Signs

The cardinal physical findings are decreased/absent femoral pulses and blood pressure gradient between the arms and legs. Normally, blood pressure in the legs is at least that of the arms, and typically higher. This is reversed in coarctation, with upper extremity blood pressure often greater than 15 mm Hg above that of lower extremities; the gradient may be diminished in the setting of significant LV dysfunction or collateralization. Blood pressure should be measured in all four extremities; the left subclavian artery may be distal to the coarctation, with decreased blood pressure and pulses in the left upper extremity. Lower extremity pulses may be normal until the PDA closes (ductal patency ensures flow to the descending aorta distal to the coarctation).

Approximately 40% of children with coarctation present as neonates, often with acute LV dysfunction, low cardiac output, shock and systemic acidosis from impaired tissue perfusion when the PDA closes. The remaining 60% of children with coarctation often have no symptoms in infancy, presenting insidiously with systemic hypertension, claudication, or failure to thrive. A systolic or continuous murmur may be present in the left back or left axilla, in addition to possible findings associated with a bicuspid aortic valve, if present.

B. Imaging

Infants with coarctation and associated cardiac dysfunction often have marked cardiac enlargement and pulmonary venous congestion on chest radiograph. Older children may have normal LV size but demonstrate a “figure 3” sign (prominent aorta proximal to the coarctation, an indentation at the level of the coarctation, and postcoarctation dilation) or inferior notching of the ribs due to significant collateralization of intercostal arteries bypassing the obstruction. CT and MRI are occasionally utilized to provide three-dimensional imaging of the aorta, especially with complex coarctation and extensive aortic hypoplasia.

C. Electrocardiography

The ECG in infants is often normal, with dominant RV forces, as the RV serves as the systemic ventricle during fetal life. ECGs in older children often demonstrate LVH.

D. Echocardiography

Two-dimensional echocardiography can directly visualize the coarctation, ventricular size and function. Color-flow and spectral Doppler demonstrate turbulent flow at the coarctation and estimate velocity across the obstruction; diastolic runoff flow is present with significant obstruction. In neonates with a PDA, future development of a coarctation cannot be excluded, as PDA closure can constrict aortic tissue, causing coarctation. Other left heart obstructive lesions, such as bicuspid aortic valve or mitral abnormalities, may be present.

E. Cardiac Catheterization and Angiocardiography

Cardiac catheterization and angiocardiography are rarely performed for diagnosis in infants or children with coarctation but are used if transcatheter intervention is planned.

Treatment

Infants with coarctation of the aorta may present in extremis, and the primary resuscitative measure is PGE₁ infusion (0.05–0.1 mcg/kg/min) to reopen the ductus arteriosus and relax ductal tissue in the aorta. End-organ damage distal to the coarctation is not uncommon, and inotropic support is frequently needed.

Once stabilized, the infant should undergo corrective repair. Neonatal repair of native coarctation is typically addressed with surgery (extended end-to-end anastomosis); surgery may also address other associated lesions at that time. Palliative neonatal balloon angioplasty of native coarctation is rarely performed in those with substantial cardiac dysfunction. In older children, balloon angioplasty of the coarctation can be the definitive treatment; stenting (including covered stent placement) may be appropriate if the stent implanted can be expanded to an adult size.

Recurrent coarctation, the primary complication of both baseline surgery and balloon angioplasty, is more common after initial angioplasty intervention. Recurrent coarctation is typically treatable in the catheterization laboratory with angioplasty and possible stent placement.

Course & Prognosis

Children who survive the neonatal period without HF do well through childhood and adolescence. Systemic hypertension is common, even after successful coarctation repair, especially in those repaired after age 5 years. Fatal complications (eg, hypertensive encephalopathy or intracranial bleeding) are uncommon in childhood. Infective endarteritis is rare before adolescence but can occur in both repaired and unrepaired coarctation. Exercise testing is mandatory prior to participation in competitive athletic activities.

2. Aortic Stenosis

General Considerations

Aortic stenosis, accounting for 3%–8% of congenital heart disease, is defined as obstruction to outflow from the LV at/near the aortic valve, producing a systolic pressure gradient greater than 10 mm Hg. Three isolated anatomic variants of aortic stenosis exist (at, below, or above the valve), though multiple levels of obstruction commonly occur.

A. Valvular Aortic Stenosis (60%–75%)

Valvular aortic stenosis has a male predominance (3–5:1) and is typically associated with a bicuspid or unicuspid aortic valve. Bicuspid aortic valve is present in 1.3% of the population, making it the most common congenital heart lesion; the valve is composed of only two leaflets or three leaflets with complete or partial fusion of two of the leaflets. A unicuspid aortic valve has fusion of the three leaflets. Leaflet fusion typically results in reduced leaflet mobility and potential obstruction to flow.

B. Subvalvular Aortic Stenosis (10%–20%)

Subvalvular aortic stenosis, also with a male predominance (2–3:1), is associated with a discrete membrane or muscular narrowing in the LV outflow tract. The aortic valve may be normal or malformed, and membranes are often attached to the anterior leaflet of the mitral valve. Membranes typically develop postnatally, often associated with other left heart obstructive lesions and perimembranous VSDs, and they are typically progressive.

C. Supravalvular Aortic Stenosis (8%–14%)

Supravalvular aortic stenosis involves narrowing of the ascending aorta, typically at the aortic sinotubular junction. This is typically associated with an elastin defect, such as in Williams syndrome (with supravalvular pulmonary stenosis, abnormal facies, and developmental delays).

Clinical Findings

A. Symptoms and Signs

Isolated valvular aortic stenosis seldom causes symptoms in infancy, though severe congenital stenosis can be associated with severe LV dysfunction and cardiogenic shock and require a PDA to supply systemic cardiac output (“critical” aortic stenosis). Physical findings vary depending on the level of obstruction:

1. Valvular aortic stenosis

If the stenosis is severe, pulses are diminished with a slow upstroke. Palpation reveals an LV thrust at the apex and, possibly, a systolic thrill at the suprasternal notch and over the carotid arteries with moderate or severe stenosis.

An aortic ejection click, associated with valve opening, may be heard at the apex, distinct from S₁ and without respiratory variation. A loud, harsh, medium-to-high-pitched ejection-type systolic murmur is present at the right upper sternal border, radiating to the suprasternal notch and carotids; the frequency of the murmur correlates with stenosis severity.

2. Discrete membranous subvalvular aortic stenosis

The findings are the same as those of valvular aortic stenosis, though an ejection click is absent. The murmur is located lower on the left sternal border, in the third and fourth intercostal spaces. Associated aortic insufficiency, a common sequela of subaortic stenosis, may have a high-pitch diastolic decrescendo murmur.

3. Supravalvular aortic stenosis

The harsh systolic murmur is best heard in the suprasternal notch (with possible thrill) and carotids but is well transmitted over the aortic area. There may be a difference in pulses and blood pressure between the right and left arms, with more prominent pulse and higher pressure in the right arm (the Coanda effect).

Most patients with aortic stenosis who do not present in infancy have no cardiovascular symptoms. Except in the most severe cases, patients do well until the third to fifth decades of life. Some patients have mild exercise intolerance and fatigability. Infrequently, significant symptoms (eg, exertional chest pain, dizziness, syncope) manifest in the first decade. Sudden death is uncommon but may occur in all forms of aortic stenosis, with the greatest risk in patients with subvalvular obstruction.

B. Imaging

In most cases, the heart is not enlarged. The LV, however, may be slightly prominent. In valvular aortic stenosis, poststenotic dilation of the ascending aorta is common.

C. Electrocardiography

Patients with mild aortic stenosis have normal ECGs. LVH and LV strain may be present with more severe obstruction, but even those with severe stenosis may have a normal ECG in up 30%. Progressive LVH on serial ECGs indicates a significant obstruction. LV strain is one indication for intervention.

D. Echocardiography

This reliable noninvasive technique can be used to diagnose and follow all forms of aortic stenosis. Two-dimensional images and color Doppler can visualize the affected area, and the mean gradient estimated by spectral Doppler approximates the transvalvular gradient by cardiac catheterization.

E. Cardiac Catheterization and Angiocardiography

Left heart catheterization demonstrates the pressure gradient from LV to aorta and the anatomic level at which the gradient exists. Catheterization should be considered for severe valvular aortic stenosis (mean gradient > 40 mm Hg, peak gradient > 70 mm Hg by echocardiography), and those with critical aortic stenosis or decreased LV function regardless of gradient.

Treatment

PGE₁ infusion is necessary in critical aortic stenosis patients until surgical or percutaneous therapy can be performed. Percutaneous balloon valvuloplasty is usually the standard initial treatment for patients with valvular aortic stenosis, though it is typically ineffective for significant annular hypoplasia or subvalvular and supravalvular stenosis. Surgery should be considered in patients with a high residual resting gradient despite balloon angioplasty or coexisting aortic insufficiency. In many cases, the gradient cannot be significantly diminished by valvuloplasty without producing aortic insufficiency. Patients who develop significant aortic insufficiency require surgical intervention to repair/replace the valve. Surgical options include a mechanical aortic valve in older children big enough to receive an adult-size valve or a Ross procedure in infants and children; the latter consists of translocating the patient’s pulmonary valve to the aortic position and placing an RV-to-pulmonary artery conduit.

Discrete subvalvular aortic stenosis is surgically removed, often at lower gradients than valvular stenosis to prevent progressive damage to the aortic valve by turbulent flow which may produce aortic insufficiency. Unfortunately, simple resection is followed by recurrence in up to 20%; additional muscle resection lowers this risk but is associated with potential heart block or iatrogenic VSD creation.

Supravalvar aortic stenosis requiring repair is usually addressed with surgical patch augmentation of the affected area. Recurrent stenosis is common, as is new stenosis development beyond repair sites.

Course & Prognosis

All forms of LV outflow tract obstruction tend to be progressive. Despite this, with the exception of those with critical aortic stenosis in infancy, patients are usually asymptomatic. Symptoms such as angina, syncope, or HF are rare but imply serious disease. Children often have normal oxygen consumption and exercise capacity with less-than-moderate stenosis. Children with mild stenosis and normal exercise stress tests may safely participate in vigorous physical activity, including non-isometric competitive sports. Those with moderate stenosis may have restrictions based on symptoms and exercise testing. Children with severe aortic stenosis are predisposed to ventricular dysrhythmias and should refrain from vigorous activity and all isometric exercise.

3. Mitral Valve Prolapse

General Considerations

In this condition as the mitral valve closes during systole, it moves posteriorly or superiorly (prolapses) into the left atrium. Mitral valve prolapse (MVP) occurs in about 2% of thin female adolescents, a minority of whom have concomitant mitral insufficiency. Although MVP is usually an isolated lesion, it can occur in association with connective tissue disorders such as Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes.

Clinical Findings

A. Symptoms and Signs

Most patients with MVP are asymptomatic. Chest pain, palpitations, and dizziness may be reported, but it is unclear whether these symptoms are more common in affected patients than in the normal population. Chest pain on exertion is rare and should be assessed with cardiopulmonary stress testing. Significant dysrhythmias have been reported, including increased ventricular ectopy and nonsustained ventricular tachycardia. If significant mitral regurgitation (MR) is present, atrial arrhythmias may also occur. Standard auscultation technique must be modified to diagnose MVP. A midsystolic click (with or without a systolic murmur) is elicited best in the standing position and is the hallmark of this entity. Conversely, maneuvers that increase LV volume, such as squatting or handgrip exercise, will cause delay or obliteration of the click-murmur complex. The systolic click usually is heard at the apex but may be audible at the left sternal border. A late, short systolic murmur after the click implies mitral insufficiency and is much less common than isolated prolapse. The murmur is not holosystolic, in contrast to rheumatic mitral insufficiency.

B. Imaging

Most chest radiographs are normal and are not usually indicated in this condition. In the rare case of significant mitral valve insufficiency, the left atrium may be enlarged.

C. Electrocardiography

The ECG is usually normal. Diffuse flattening or inversion of T waves may occur in the precordial leads. U waves are sometimes prominent.

D. Echocardiography

Echocardiography assesses the degree of myxomatous change of the mitral valve and the degree of mitral insufficiency. Significant posterior systolic movement of the mitral valve leaflets to the atrial side of the mitral annulus is diagnostic.

E. Other Testing

Invasive procedures are rarely indicated. Holter monitoring or event recorders may be useful in establishing the presence of ventricular dysrhythmias in patients with palpitations.

Treatment & Prognosis

Propranolol may be effective in treatment of coexisting arrhythmias. Prophylaxis for infectious endocarditis is no longer indicated, based on 2007 AHA guidelines. The natural course of this condition is not well defined. Twenty years of observation indicate that isolated MVP in childhood is usually a benign entity. Surgery for mitral insufficiency is rarely needed.

4. Other Congenital Left Heart Valvular Lesions

A. Congenital Mitral Stenosis

Congenital mitral stenosis is a rare disorder in which the valve leaflets are thickened and/or fused, producing a diaphragm- or funnel-like structure with a central opening. In many cases, the subvalve apparatus (papillary muscles and chordae) is also abnormal. When mitral stenosis occurs with other left-sided obstructive lesions, such as subaortic stenosis and coarctation of the aorta, the complex is called Shone syndrome. Most patients develop symptoms early in life with tachypnea, dyspnea, and failure to thrive. Physical examination reveals an accentuated S₁ and a loud pulmonary closure sound. No opening snap is heard. In most cases, a presystolic crescendo murmur is heard at the apex. Occasionally, only a mid-diastolic murmur can be heard. ECG shows right-axis deviation, biatrial enlargement, and RVH. Chest radiograph reveals left atrial enlargement and frequent pulmonary venous congestion. Echocardiography shows abnormal mitral valve structures with reduced leaflet excursion and left atrial enlargement. Cardiac catheterization reveals an elevated pulmonary capillary wedge pressure and PH, owing to the elevated left atrial pressure.

Mitral valve repair or mitral valve replacement with a prosthetic mitral valve may be performed, even in young infants, but it is a technically difficult procedure. Mitral valve repair is the preferred surgical option, as valve replacement can have a poor outcome in infants.

B. Cor Triatriatum

Cor triatriatum is a rare abnormality in which the pulmonary veins join in a confluence that is not completely incorporated into the left atrium. The pulmonary vein confluence communicates with the left atrium through an opening of variable size and may be obstructed. Patients may present in a similar way as those with mitral stenosis. Clinical findings depend on the degree of obstruction of pulmonary venous flow into the left atrium. If the communication between the confluence and the left atrium is small and restrictive to flow, symptoms develop early in life. Echocardiography reveals a linear density in the left atrium with a pressure gradient present between the pulmonary venous chamber and the true left atrium. Cardiac catheterization may be needed if the diagnosis is in doubt. High pulmonary wedge pressure and low left atrial pressure (with the catheter passed through the foramen ovale into the true left atrium) support the diagnosis. Angiocardiography identifies the pulmonary vein confluence and the anatomic left atria. Surgical repair is always required in the presence of an obstructive membrane, and long-term results are good. Coexisting mitral valve abnormalities may be noted, including a supravalvular mitral ring or a dysplastic mitral valve.

DISEASES OF THE AORTA

Patients at risk for progressive aortic dilation and dissection include those with isolated bicuspid aortic valve, Marfan syndrome, Loeys-Dietz syndrome, Turner syndrome, and type IV Ehlers-Danlos syndrome.

1. Bicuspid Aortic Valve

Patients with bicuspid aortic valves have an increased incidence of aortic dilation and dissection, regardless of the presence of aortic stenosis. Histologic examination demonstrates cystic medial degeneration of the aortic wall, similar to that seen in patients with Marfan syndrome. Patients with an isolated bicuspid aortic valve require regular follow-up even in the absence of aortic insufficiency or aortic stenosis. Significant aortic root dilation requiring surgical intervention typically does not occur until adulthood.

2. Marfan & Loeys-Dietz Syndromes

Marfan syndrome is an autosomal dominant disorder of connective tissue caused by a mutation in the fibrillin-1 gene. Spontaneous mutations account for 25%–30% of cases, and thus family history is not always helpful. Patients are diagnosed by the Ghent criteria and must have at a minimum, major involvement of two body systems plus involvement of a third body system or a positive family history. Body systems involved include cardiovascular, ocular, musculoskeletal, pulmonary, and integumentary. Cardiac manifestations include aortic root dilation and MVP, which may be present at birth. Patients are at risk for aortic dilation and dissection and are restricted from competitive athletics, contact sports, and isometric activities. β-Blockers (eg, atenolol), ACE inhibitors, or angiotensin receptor blockers (eg, losartan) are used to lower blood pressure and slow the rate of aortic dilation. A recent study of atenolol versus losartan in children and young adults with Marfan syndrome showed no difference in the rate of aortic dilation between the two medications. Elective surgical intervention is performed in patients of adult size when the aortic root dimension reaches 50 mm or if there is an increase of greater than 1 cm in root dimension in 1 year. The ratio of actual to expected aortic root dimension is used to determine the need for surgery in the young child. Surgical options include replacement of the dilated aortic root with a composite valve graft (Bentall technique) or a David procedure in which the patient’s own aortic valve is spared and a Dacron tube graft is used to replace the dilated ascending aorta. Young age at diagnosis was previously thought to confer a poor prognosis; however, early diagnosis with close follow-up and early medical therapy has more recently been associated with more favorable outcome. Ventricular dysrhythmias may contribute to the mortality in Marfan syndrome.

Loeys-Dietz syndrome is a connective tissue disorder first described in 2005. Many patients with Loeys-Dietz were thought to have Marfan syndrome in the past. Loeys-Dietz is a result of a mutation in the transforming growth factor β (TGFβ) receptor and is associated with musculoskeletal, skin, and cardiovascular abnormalities. Cardiovascular involvement includes mitral and tricuspid valve prolapse, aneurysms of the PDA, and aortic and pulmonary artery dilation. Dissection and aneurysm formation of arteries throughout the body can occur including in the head and neck vessels.

3. Turner Syndrome

Cardiovascular abnormalities are common in Turner syndrome. Patients are at risk for aortic dissection, typically during adulthood. Risk factors include hypertension regardless of cause, aortic dilation, bicuspid aortic valve, and coarctation of the aorta. There are rare reports of aortic dissection in adult Turner syndrome patients in the absence of any risk factors suggesting that there is a vasculopathic component to this syndrome. Patients with Turner syndrome require routine follow-up from adolescence onward to monitor for this potentially lethal complication.

CORONARY ARTERY ABNORMALITIES

Several anomalies involve the origin, course, and distribution of the coronary arteries. Abnormal origin or course of the coronary arteries are often asymptomatic and can go undetected. However, in some instances these children are at risk for sudden death. The most common congenital coronary artery abnormality in infants is anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and is discussed in more detail here.

Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery

In this condition, the left coronary artery arises from the pulmonary artery rather than the aorta. In neonates, whose PAP is high, perfusion of the left coronary artery may be adequate and the infant may be asymptomatic. By age 2 months the pulmonary arterial pressure falls, causing a progressive decrease in myocardial perfusion provided by the anomalous left coronary artery. Ischemia and infarction of the LV is the result. Immediate surgery is indicated to reimplant the left coronary artery and restore myocardial perfusion.

Clinical Findings

A. Symptoms and Signs

Neonates appear healthy and growth and development are relatively normal until PAP decreases. Detailed questioning may disclose a history of intermittent abdominal pain (fussiness or irritability), pallor, wheezing, and sweating, especially during or after feeding. Presentation may be subtle, with nonspecific complaints of “fussiness” or intermittent “colic.” The colic and fussiness are probably attacks of true angina. Presentation may be fulminant at age 2–4 months with sudden, severe HF due to LV dysfunction and mitral insufficiency. On physical examination, the infants are usually well developed and well nourished. The pulses are typically weak but equal. A prominent left precordial bulge is present. A gallop and/or holosystolic murmur of MR is sometimes present, though frequently auscultation alone reveals no obvious abnormalities.

B. Imaging

Chest radiographs show cardiac enlargement, left atrial enlargement, and may show pulmonary venous congestion if LV function has been compromised.

C. Electrocardiography

On the ECG, there is T-wave inversion in leads I and aVL. The precordial leads also show T-wave inversion from V₄–V₇. Deep and wide Q waves are present in leads I, aVL, and sometimes in V₄–V₆. These findings of myocardial infarction are similar to those in adults.

D. Echocardiography

The diagnosis can be made with two-dimensional echo techniques by visualizing a single large right coronary artery arising from the aorta and visualization of the anomalous left coronary artery arising from the main pulmonary artery. Flow reversal in the left coronary (heading toward the pulmonary artery, rather than away from the aorta) confirms the diagnosis. LV dysfunction, echo-bright (ischemic) papillary muscles, and MR are commonly seen.

E. Cardiac Catheterization and Angiocardiography

Angiogram of the aorta fails to show the origin of the left coronary artery. A large right coronary artery fills directly from the aorta, and contrast flows from the right coronary system via collaterals into the left coronary artery and finally into the pulmonary artery. Angiogram of the RV or main pulmonary artery may show the origin of the anomalous vessel. Rarely, a left-to-right shunt may be detected as oxygenated blood passes through the collateral system without delivering oxygen to the myocardium, and passes into the pulmonary artery.

Treatment & Prognosis

The prognosis of ALCAPA depends in part on the clinical appearance of the patient at presentation. Medical management with diuretics and afterload reduction can help stabilize a critically ill patient, but surgical intervention should not be delayed. Surgery involves reimplantation of the anomalous coronary button onto the aorta. The mitral valve may have to be replaced, depending on the degree of injury to the papillary muscles and associated mitral insufficiency. Although a life-threatening problem, cardiac function nearly always recovers if the infant survives the surgery and postoperative period.

TETRALOGY OF FALLOT

General Considerations

In tetralogy of Fallot (ToF), anterior deviation of the infundibular (pulmonary outflow) septum causes narrowing of the RV outflow tract. This deviation also results in a VSD and the aorta then overrides the crest of the ventricular septum. The RV hypertrophies, not because of pulmonary stenosis, but because it is pumping against systemic resistance across a (usually) large VSD. ToF is the most common cyanotic cardiac lesion and accounts for 10% of all congenital heart disease. A right-sided aortic arch is present in 25% of cases, and ASD occurs in 15%.

Obstruction to RV outflow with a large VSD causes a right-to-left shunt at the ventricular level with arterial desaturation. The greater the obstruction and the lower the systemic vascular resistance, the greater is the right-to-left shunt. ToF is associated with deletions in the long arm of chromosome 22 (22q11, DiGeorge syndrome) in as many as 15% of affected children. This is especially common in those with an associated right aortic arch.

Clinical Findings

A. Symptoms and Signs

Clinical findings vary with the degree of RV outflow obstruction. Patients with mild obstruction are minimally cyanotic or acyanotic. Those with severe obstruction are deeply cyanotic from birth. Few children are asymptomatic. In those with significant RV outflow obstruction, many have cyanosis at birth, and nearly all have cyanosis by age 4 months. The cyanosis usually is progressive, as subvalvular obstruction increases. Growth and development are not typically delayed, but easy fatigability and dyspnea on exertion are common. The fingers and toes show variable clubbing depending on age and severity of cyanosis. Historically, older children with ToF would frequently squat to increase systemic vascular resistance. This decreased the amount of right-to-left shunt, forcing blood through the pulmonary circuit, and would help ward off cyanotic spells. Squatting is rarely seen as the diagnosis is now made in infancy.

Hypoxemic spells, also called cyanotic or “Tet spells,” are one of the hallmarks of severe ToF. These spells can occur spontaneously and at any time but in infants occur most commonly with crying or feeding, while in older children they can occur with exercise. They are characterized by (1) sudden onset of cyanosis or deepening of cyanosis; (2) dyspnea; (3) alterations in consciousness, from irritability to syncope; and (4) decrease in or disappearance of the systolic murmur (as RV the outflow tract becomes completely obstructed). These episodes most commonly start at age 4–6 months. Cyanotic spells are treated acutely by administration of oxygen and placing the patient in the knee-chest position (to increase systemic vascular resistance). Intravenous morphine should be administered cautiously but is helpful for its sedative effect. Propranolol produces β-blockade and may reduce the obstruction across the RV outflow tract through its negative inotropic action. Acidosis, if present, should be corrected with intravenous sodium bicarbonate. Chronic oral prophylaxis of cyanotic spells with propranolol may be useful to delay surgery, but the onset of Tet spells usually prompts surgical intervention. In fact, in the current era, elective surgical repair generally occurs around the age of 3 months so as to avoid the development of Tet spells.

On examination, an RV lift is palpable. S₂ is predominantly aortic and single. A grade II–IV/VI, rough, systolic ejection murmur is present at the left sternal border in the third intercostal space and radiates well to the back.

B. Laboratory Findings

Hemoglobin, hematocrit, and red blood cell count are usually elevated in older infants or children secondary to chronic arterial desaturation.

C. Imaging

Chest radiographs show a normal-size heart. The RV is hypertrophied, often shown by an upturning of the apex (boot-shaped heart). The main pulmonary artery segment is usually concave, and if there is a right aortic arch, the aortic knob is to the right of the trachea. The pulmonary vascular markings are usually decreased.

D. Electrocardiography

The QRS axis is rightward, ranging from +90 to +180 degrees. The P waves are usually normal. RVH is always present, but RV strain patterns are rare.

E. Echocardiography

Two-dimensional imaging is diagnostic, revealing thickening of the RV wall, overriding of the aorta, and a large subaortic VSD. Obstruction at the level of the infundibulum and pulmonary valve can be identified, and the size of the proximal pulmonary arteries measured. The anatomy of the coronary arteries should be visualized, as abnormal branches crossing the RV outflow tract are at risk for transection during surgical enlargement of the area.

F. Cardiac Catheterization and Angiocardiography

Cardiac catheterization is generally done mainly in those patients with hypoplastic pulmonary arteries. If a catheterization is done, it reveals a right-to-left shunt at the ventricular level in most cases. Arterial desaturation of varying degrees is present. The RV pressure is at systemic levels and the pressure tracing in the RV is identical to that in the LV if the VSD is large. The PAP is invariably low. Pressure gradients may be noted at the pulmonary valvular level, the infundibular level, or both. RV angiography reveals RV outflow obstruction and a right-to-left shunt at the ventricular level. The major indications for cardiac catheterization are to establish coronary artery and distal pulmonary artery anatomy if not able to be clearly defined by echocardiography.

Treatment

A. Palliative Treatment

Most centers currently advocate complete repair of ToF during the neonatal or infant period regardless of patient size. However, some centers prefer palliative treatment for small neonates in whom complete correction is deemed risky. Surgical palliation consists of the insertion of a GoreTex shunt from the subclavian artery to the ipsilateral pulmonary artery [modified Blalock-Taussig (BT) shunt] to replace the ductus arteriosus (which is ligated and divided) or stenting of the ductus. This secures a source of pulmonary blood flow regardless of the level of infundibular or valvular obstruction and, as some believe, allows for growth of the patient’s pulmonary arteries (which are usually small) prior to complete surgical correction.

B. Total Correction

Open-heart surgery for repair of ToF is performed at ages ranging from birth to 2 years, depending on the patient’s anatomy and the experience of the surgical center. The current surgical trend is toward earlier repair for symptomatic infants. The major limiting anatomic feature of total correction is the size of the pulmonary arteries. During surgery, the VSD is closed and the obstruction to RV outflow removed. Although a valve sparing procedure is preferred, in many cases a transannular patch is placed across the RV outflow tract as the pulmonary valve is contributing to the obstruction. When a transannular patch repair is done, the patient has PI that is usually well tolerated for years. However, pulmonary valve replacement is eventually necessary once symptoms (usually exercise intolerance) and RV dilation occur. Surgical mortality is low.

Course & Prognosis

Infants with severe ToF are usually deeply cyanotic at birth. These children require early surgery. Complete repair before age 2 years usually produces a good result, and patients are currently living well into adulthood. Depending on the extent of the repair required, patients frequently require additional surgery 10–15 years after their initial repair for replacement of the pulmonary valve. Transcatheter pulmonary valves are now performed in some adolescents and young adults with a history of ToF, avoiding the need for open heart surgery. Patients with ToF are at risk for sudden death due to ventricular dysrhythmias. A competent pulmonary valve without a dilated RV appears to diminish arrhythmias and enhance exercise performance.

PULMONARY ATRESIA WITH VENTRICULAR SEPTAL DEFECT

Complete atresia of the pulmonary valve in association with a VSD is essentially an extreme form of ToF. Because there is no antegrade flow from the RV to the pulmonary artery, pulmonary blood flow must be derived from a PDA or from multiple aortopulmonary collateral arteries (MAPCAs). Symptoms depend on the amount of pulmonary blood flow. If flow is adequate, patients may be stable. If pulmonary flow is inadequate, severe hypoxemia occurs and immediate palliation is required. Newborns are stabilized with intravenous prostaglandin E₁ (PGE₁) to maintain the PDA while being prepared for surgery. Rarely, if the ductus does not contribute significantly to pulmonary blood flow (eg, the MAPCAs alone are sufficient), PGE₁ may be discontinued. Once stabilized, a BT shunt, stenting of the ductus or complete repair is undertaken. The decision to perform palliation or complete repair in a newborn is dependent on surgical expertise and preference in combination with pulmonary artery anatomy. In many centers, a palliative shunt is performed in newborns with severely hypoplastic pulmonary arteries or in those with only MAPCAs as a source of pulmonary blood flow. The goal of the shunt is to augment pulmonary blood flow and encourage vascular growth, and open-heart surgical correction is planned several months later. In children with MAPCAs, relocation of the MAPCAs is performed so that they are connected to the pulmonary artery (unifocalization) to complete the repair.

Echocardiography is usually diagnostic. Cardiac catheterization and angiocardiography or cardiac MRI can confirm the source(s) of pulmonary blood flow and document size of the distal pulmonary arteries.

Pulmonary vascular disease is common in PA with VSD, due both to intrinsic abnormalities of the pulmonary vasculature and to abnormal amounts of pulmonary blood flow. Even patients who have undergone surgical correction as infants are at risk. Pulmonary vascular disease is a common cause of death as early as the third decade of life.

PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM

General Considerations

Although pulmonary atresia with intact ventricular septum (PA/IVS) sounds as if it might be related to PA with VSD, it is a distinct cardiac condition. As the name suggests, the pulmonary valve is atretic. The pulmonic annulus usually has a small diaphragm consisting of the fused valve cusps. The ventricular septum is intact. The main pulmonary artery segment is usually present and closely approximated to the atretic valve but is somewhat hypoplastic. Although the RV is always reduced in size, the degree of reduction is variable. The size of the RV is critical to the success of surgical repair. In some children with PA/IVS, the RV is adequate for an ultimate two-ventricular repair. A normal RV has three component parts (inlet, trabecular or body, and outlet). The absence of any one of the components makes adequate RV function unlikely and a single ventricle palliative approach is necessary. Even with all three components, some RVs are inadequate.

After birth, the pulmonary flow is provided by the ductus arteriosus. MAPCAs are usually not present in this disease, in contrast to PA with VSD. A continuous infusion of PGE₁ must be started as soon as possible after birth to maintain ductal patency.

Clinical Findings

A. Symptoms and Signs

Neonates are usually cyanotic and become more so as the ductus arteriosus closes. A blowing systolic murmur resulting from the associated PDA may be heard at the pulmonary area. A holosystolic murmur is often heard at the lower left sternal border, as many children develop tricuspid insufficiency if the RV is of good size and egress from that ventricle is only through the tricuspid valve. A PFO or ASD is essential for decompression of the right side of the heart.

B. Imaging

The heart size varies depending on the degree of tricuspid insufficiency. With severe tricuspid insufficiency, right atrial enlargement may be massive and the cardiac silhouette may fill the chest on radiograph. In patients with an associated hypoplastic tricuspid valve and or RV, most of the systemic venous return travels right-to-left across the ASD, and so the heart size can be normal.

C. Electrocardiography

ECG reveals a left axis for age (45–90 degrees) in the frontal plane. LV forces dominate the ECG, and there is a paucity of RV forces, particularly with a hypoplastic RV. Findings of right atrial enlargement are usually striking.

D. Echocardiography

Echocardiography shows atresia of the pulmonary valve with varying degrees of RV cavity and tricuspid annulus hypoplasia. Patency of an intra-atrial communication and ductus are verified by echocardiography.

E. Cardiac Catheterization and Angiocardiography

RV pressure is often suprasystemic. Angiogram of the RV reveals no filling of the pulmonary artery. Unrestricted flow through the ASD is a necessity, since egress of blood from the right heart can only occur across the atrial defect and into the left atrium. A Rashkind balloon atrial septostomy may be required to open any inadequate existing communication across the atrial septum. Some children with PA and IVS have sinusoids between the RV and the coronary arteries. In some patients, the coronary circulation may depend on high RV pressure. Any attempt to decompress the RV in patients with RV-dependent coronary circulation causes myocardial infarction and death because of the precipitous decrease in coronary perfusion, so precise coronary angiography is required to evaluate the anatomy. If the RV is tripartite, coronary circulation is not RV-dependent and an eventual two-chamber repair is planned. The pulmonary valve plate may be perforated and dilated during cardiac catheterization in the newborn to allow antegrade flow from the RV to the pulmonary artery and thus encourage RV cavity growth.

Treatment & Prognosis

As in all ductal-dependent lesions, PGE₁ is used to stabilize the patient and maintain patency of the ductus until surgery can be performed. Surgery is usually undertaken in the first week of life. If the RV is hypoplastic, significant sinusoids are present, there is RV-dependent coronary circulation (lack of antegrade filling of the coronaries from the aorta), or the pulmonic valve cannot be opened successfully during cardiac catheterization, a BT shunt or ductal stenting is performed to establish pulmonary blood flow. Later in infancy, a communication between the RV and pulmonary artery can be created to stimulate RV cavity growth. If either RV dimension or function is inadequate for two-ventricular repair, an approach similar to that taken for a single ventricle pathway best serves these children (see section Hypoplastic Left Heart Syndrome). Children with significant sinusoids or coronary artery abnormalities are considered for cardiac transplantation because they are at risk for coronary insufficiency and sudden death.

The prognosis in this condition is guarded.

TRICUSPID ATRESIA

General Considerations

In tricuspid atresia, there is complete atresia of the tricuspid valve with no direct communication between the right atrium and the RV. There are two types of tricuspid atresia based on the relationship of the great arteries (normally related or transposed great arteries). The entire systemic venous return must flow through the atrial septum (either ASD or PFO) to reach the left atrium. The left atrium thus receives both the systemic venous return and the pulmonary venous return. Complete mixing occurs in the left atrium, resulting in variable degrees of arterial desaturation.

Because there is no flow to the RV, development of the RV depends on the presence of a ventricular left-to-right shunt. Severe hypoplasia of the RV occurs when there is no VSD or when the VSD is small.

Clinical Findings

A. Symptoms and Signs

Symptoms usually develop in early infancy with cyanosis present at birth in most infants. Growth and development are poor, and the infant usually exhibits exhaustion during feedings, tachypnea, and dyspnea. Patients with increased pulmonary blood flow may develop HF with less prominent cyanosis. The degree of pulmonary blood flow is most dependent on PVR. Those patients with low PVR will have increased pulmonary blood flow. A murmur from the VSD is usually present and heard best at the lower left sternal border. Digital clubbing is present in older children with long-standing cyanosis.

B. Imaging

The heart is slightly to markedly enlarged. The main pulmonary artery segment is usually small or absent. The size of the right atrium is moderately to massively enlarged, depending on the size of the communication at the atrial level. The pulmonary vascular markings are usually decreased. Pulmonary vascular markings may be increased if pulmonary blood flow is not restricted by the VSD or pulmonary stenosis.

C. Electrocardiography

The ECG shows marked left-axis deviation. The P waves are tall and peaked, indicative of right atrial hypertrophy. LVH or LV dominance is found in almost all cases. RV forces on the ECG are usually low or absent.

D. Echocardiography

Two-dimensional echocardiography is diagnostic and show absence of the tricuspid valve, the relationship between the great arteries, the anatomy of the VSD, presence of an ASD or PFO, and the size of the pulmonary arteries. Color-flow Doppler imaging can help identify atrial level shunting and levels of restriction of pulmonary blood flow, either at the VSD or in the RV outflow tract.

E. Cardiac Catheterization and Angiocardiography

Catheterization reveals a right-to-left shunt at the atrial level. Because of mixing in the left atrium, oxygen saturations in the LV, RV, pulmonary artery, and aorta are identical to those in the left atrium. Right atrial pressure is increased if the ASD is restrictive. LV and systemic pressures are normal. The catheter cannot be passed through the tricuspid valve from the right atrium to the RV. A balloon atrial septostomy is performed if a restrictive PFO or ASD is present.

Treatment & Prognosis

In infants with unrestricted pulmonary blood flow, conventional anticongestive therapy with diuretics and afterload reduction should be given until the infant begins to outgrow the VSD. Sometimes, a pulmonary artery band is needed to protect the pulmonary bed from excessive flow and development of pulmonary vascular disease.

Staged palliation of tricuspid atresia is the usual surgical approach. In infants with diminished pulmonary blood flow, PGE₁ is given until an aortopulmonary shunt (BT shunt or ductal stent) can be performed. A Glenn procedure (SVC to pulmonary artery anastomosis) is done with takedown of the aortopulmonary/BT shunt at 4–6 months when saturations begin to fall, and completion of the Fontan procedure (redirection of IVC and SVC to pulmonary artery) is performed when the child reaches around 15 kg.

The long-term prognosis for children treated by the Fontan procedure is unknown, although patients now are living into their late 20s and early 30s. In the short term, the best results for the Fontan procedure occur in children with low PAPs prior to open-heart surgery.

HYPOPLASTIC LEFT HEART SYNDROME

General Considerations

Hypoplastic left heart syndrome (HLHS) includes several conditions in which obstructive lesions of the left heart are associated with hypoplasia of the LV. The syndrome occurs in 1.4%–3.8% of infants with congenital heart disease.

Stenosis or atresia of the mitral and aortic valves is the rule. In the neonate, survival depends on a PDA because antegrade flow into the systemic circulation is inadequate or nonexistent. The PDA provides the only flow to the aorta and coronary arteries. Children with HLHS are usually stable at birth, but they deteriorate rapidly as the ductus closes in the first week of life. Untreated, the average age at death is the first week of life. Rarely, the ductus remains patent and infants may survive for weeks to months without PGE₁ therapy.

The diagnosis is often made prenatally by fetal echocardiography. Prenatal diagnosis aids in counseling for the expectant parents and planning for the delivery of the infant at or near a center with experience in treating HLHS.

Clinical Findings

A. Symptoms and Signs

Neonates with HLHS appear stable at birth because the ductus is patent. They deteriorate rapidly as the ductus closes, with shock and acidosis secondary to inadequate systemic perfusion. Oxygen saturation may actually increase for a period of time as the ductus closes due to increased blood flowing to the lungs.

B. Imaging

Chest radiograph in the first day of life may be relatively unremarkable, with the exception of a small cardiac silhouette. Later, chest radiographs demonstrate cardiac enlargement with severe pulmonary venous congestion if the PDA has begun closing or if the baby has been placed on supplemental oxygen increasing pulmonary blood flow.

C. Electrocardiography

The ECG shows right-axis deviation, right atrial enlargement, and RVH with a relative paucity of LV forces. The small Q wave in lead V₆ may be absent, and a qR pattern is often seen in lead V₁.

D. Echocardiography

Echocardiography is diagnostic. A hypoplastic aorta and LV with atretic or severely stenotic mitral and aortic valves are diagnostic. The systemic circulation is dependent on the PDA. Color-flow Doppler imaging shows retrograde flow in the ascending aorta, as the coronary arteries are supplied by the ductus via the small native aorta.

Treatment & Prognosis

Initiation of PGE₁ is essential and lifesaving, as systemic circulation depends on a PDA. Later management depends on balancing pulmonary and systemic blood flow both of which depend on the RV. At a few days of age the pulmonary resistance falls, favoring pulmonary overcirculation and systemic underperfusion. Therapy is then directed at encouraging systemic blood flow. Despite hypoxia and cyanosis, supplemental oxygen is avoided as this will decrease pulmonary resistance and lead to further increases in pulmonary blood flow. In some centers, nitrogen is used to decrease inspired oxygen to as low as 17%. This therapy must be carefully monitored but results in increased pulmonary arterial resistance, which encourages systemic blood flow and improves systemic perfusion. Systemic afterload reduction will also increase systemic perfusion. Adequate perfusion can usually be obtained by keeping systemic O₂ saturation between 65% and 80%, or more accurately a PO₂ of 40 mm Hg.

Staged surgical palliation is the most common management approach. In the Norwood procedure, the relatively normal main pulmonary artery is transected and connected to the small ascending aorta. The entire aortic arch must be reconstructed due to its small size. Then, either a BT shunt (from the subclavian artery to the pulmonary artery) or a Sano shunt (from the RV to the pulmonary artery) must be created to restore pulmonary blood flow. Children who have a Norwood procedure will later require a Glenn anastomosis (SVC to pulmonary artery with takedown of the systemic-pulmonary shunt) and then a Fontan (IVC to pulmonary artery, completing the systemic venous bypass of the heart) at ages 6 months and 2–3 years, respectively. Despite advances in surgical technique and postoperative care, HLHS remains one of the most challenging lesions in pediatric cardiology, with 1-year survival as low as 70%.

Orthotopic heart transplantation is also a treatment option for newborns with HLHS but in the current era is typically performed only in infants who are considered poor Norwood candidates. Heart transplantation is more commonly utilized in the event of a failed surgical palliation or if the systemic RV fails (often in adolescence or young adulthood).

Recently, some centers offer a “hybrid” approach to HLHS as a result of collaboration between surgeons and interventional cardiologists. In the hybrid procedure, the chest is opened surgically and the branch pulmonary arteries are banded, to limit pulmonary blood flow. Then, also through the open chest, a PDA stent is placed by the interventionalist to maintain systemic output. The second stage is considered a “comprehensive Glenn,” in which the pulmonary artery bands and ductal stent are taken down, the aortic arch is reconstructed and the SVC is surgically connected to the pulmonary arteries. Short-term (30 day) survival after the first-stage “hybrid” is greater than 90% at the most experienced centers, but second-stage risks and complications mitigate some of that initial survival advantage. Long-term follow-up data are not yet available.

TRANSPOSITION OF THE GREAT ARTERIES

General Considerations

Transposition of the great arteries (TGA) is the second most common cyanotic congenital heart disease, accounting for 5% of all cases of congenital heart disease. The male-to-female ratio is 3:1. It is caused by an embryologic abnormality in the spiral division of the truncus arteriosus in which the aorta arises from the RV and the pulmonary artery from the LV. This is referred to as “ventriculoarterial discordance.” Patients may have a VSD, or the ventricular septum may be intact. Left unrepaired, transposition is associated with a high incidence of early pulmonary vascular obstructive disease. Because pulmonary and systemic circulations are in parallel, survival is impossible without mixing between the two circuits. Specifically an interatrial communication (PFO or ASD) is critically important. The majority of mixing occurs at the atrial level (some mixing can occur at the level of the ductus as well), so even in the presence of a VSD an adequate interatrial communication is needed. If the atrial communication is inadequate at birth, the patient is severely cyanotic.

Clinical Findings

A. Symptoms and Signs

Many neonates are large (up to 4 kg) and profoundly cyanotic without respiratory distress or a significant murmur. Infants with a large VSD may be less cyanotic, and they usually have a prominent murmur. The findings on cardiovascular examination depend on the intracardiac defects. Obstruction to outflow from either ventricle is possible, and coarctation must be ruled out.

B. Imaging

The chest radiograph in transposition is usually nondiagnostic. Sometimes there is an “egg on a string” appearance because the aorta is directly anterior to the main pulmonary artery, giving the image of a narrow mediastinum.

C. Electrocardiography

Because the newborn ECG normally has RV predominance, the ECG in transposition is of little help, as it will frequently look normal.

D. Echocardiography

Two-dimensional imaging and Doppler evaluation demonstrate the anatomy and physiology well. The aorta arises from the RV, and the pulmonary artery arises from the LV. Associated defects, such as a VSD, RV, or LV outflow tract obstruction, or coarctation, must be evaluated. The atrial septum should be closely examined, as any restriction could prove detrimental as the child awaits repair. The coronary anatomy is variable and must be defined prior to surgery.

E. Cardiac Catheterization and Angiocardiography

A Rashkind balloon atrial septostomy is frequently performed in complete transposition if the interatrial communication is restrictive. This procedure can be done at the bedside with echocardiographic guidance in most cases. The coronary anatomy can be delineated by ascending aortography if not well seen by echocardiography.

Treatment

Early corrective surgery is recommended. The arterial switch operation (ASO) has replaced the previously performed atrial switch procedures (Mustard and Senning operations). The ASO is performed at age 4–7 days. The arteries are transected above the level of the valves and switched, while the coronaries are separately reimplanted. Small associated VSDs may be left to close on their own, but large VSDs are repaired. The ASD is also closed. Early surgical repair (< 14 days of age) is vital for patients with TGA and an IVS to avoid potential deconditioning of the LV as it pumps to the low-resistance pulmonary circulation. If a large, unrestrictive VSD is present, LV pressure is maintained at systemic levels, the LV does not become deconditioned, and corrective surgery can be delayed for a few months. Surgery should be performed by age 3–4 months in those with TGA and a VSD because of the high risk of early pulmonary vascular disease associated with this defect.

Operative survival after the ASO is greater than 95% in major centers. The main advantage of the arterial switch procedure in comparison to the atrial switch procedures (Mustard and Senning operations) is that the systemic ventricle is the LV. Patients who have undergone an atrial switch undergo surgical patch placement to baffle the venous return through the atria to the opposite ventricle. They then have an RV as their systemic ventricle, leaving them with significant late risk of RV failure, and need for heart transplantation and are at risk for atrial baffle obstruction.

1. Congenitally Corrected Transposition of the Great Arteries

Congenitally corrected transposition of the great arteries (ccTGA) is a relatively uncommon congenital heart disease. Patients may present with cyanosis, HF, or be asymptomatic, depending on the associated lesions. In ccTGA, both atrioventricular and ventriculoarterial discordance occurs so that the right atrium connects to a morphologic LV, which supports the pulmonary artery. Conversely, the left atrium empties via a tricuspid valve into a morphologic RV, which supports the aorta. Common associated lesions are VSD and pulmonary stenosis. A dysplastic left-sided tricuspid valve is almost always present. In the absence of associated lesions, patients with ccTGA are often undiagnosed until adulthood when they present with left-sided AV valve insufficiency or arrhythmias.

Previously, surgical repair was directed at VSD closure and relief of pulmonary outflow tract obstruction—a technique that maintained the RV as the systemic ventricle with outflow to the aorta. It is now recognized that these patients have a reduced life span due to systemic RV failure; thus other surgical techniques have been advocated. The double-switch procedure is one such technique. An atrial level switch (Mustard or Senning technique) is performed, in which pulmonary and systemic venous blood are baffled such that they drain into the contralateral ventricle (systemic venous return drains into the RV and pulmonary venous return drains into the LV). An ASO then restores the morphologic LV to its position as systemic ventricle.

Patients with ccTGA have an increased incidence of complete heart block with an estimated risk of 1% per year and an overall frequency of 50%.

2. Double-Outlet Right Ventricle

In this uncommon malformation, both great arteries arise from the RV. There is always a VSD that allows blood to exit the LV. Presenting symptoms depend on the relationship of the VSD to the semilunar valves. The VSD can be in variable positions, and the great arteries could be normally related or malposed. In the absence of outflow obstruction, a large left-to-right shunt exists and the clinical picture resembles that of a large VSD. Pulmonary stenosis may be present, particularly if the VSD is remote from the pulmonary artery. This physiology is similar to ToF. Alternatively, if the VSD is nearer the pulmonary artery, aortic outflow may be obstructed (called the Taussig-Bing malformation). Early primary correction is the goal. LV flow is directed to the aorta across the VSD (closing the VSD), and an RV to pulmonary artery conduit is placed to maintain unobstructed flow through the pulmonary circulation. If the aorta is far from the VSD, an arterial switch may be necessary. Echocardiography is usually sufficient to make the diagnosis and determine the orientation of the great vessels and their relationship to the VSD.

TOTAL ANOMALOUS PULMONARY VENOUS RETURN

General Considerations

This malformation accounts for 2% of all congenital heart lesions. Instead of the pulmonary veins draining into the left atrium, the veins empty into a confluence that usually is located behind the left atrium. However, the confluence is not connected to the left atrium and instead the pulmonary venous blood drains into the systemic venous system. Therefore, there is complete mixing of the systemic and pulmonary venous blood at the level of the right atrium. The presentation of a patient with total anomalous pulmonary venous return (TAPVR) depends on the route of drainage into the systemic circulation and whether or not this drainage route is obstructed.

The malformation is classified as either intra-, supra-, or infracardiac. Intracardiac TAPVR occurs when the pulmonary venous confluence drains directly into the heart, usually via the coronary sinus into the right atrium (rarely direct drainage into the right atrium). Supracardiac (or supradiaphragmatic) return is defined as a confluence that drains into the right SVC, innominate vein, or persistent left SVC. In infracardiac (or infradiaphragmatic) return, the confluence drains below the diaphragm usually into the portal venous system, which empties into the IVC. Infracardiac pulmonary venous return is very frequently obstructed. This obstruction to pulmonary venous drainage makes this lesion a potential surgical emergency. Supracardiac veins may also be obstructed, though less commonly. Rarely, the pulmonary venous confluence drains to more than one location, called mixed TAPVR.

Because the entire venous drainage from the body returns to the right atrium, a right-to-left shunt must be present at the atrial level, either as an ASD or a PFO. Occasionally, the atrial septum is restrictive and balloon septostomy is needed at birth to allow filling of the left heart.

Clinical Findings

A. Unobstructed Pulmonary Venous Return

Patients with unobstructed TAPVR and a large atrial communication tend to have high pulmonary blood flow and typically present with cardiomegaly and HF rather than cyanosis. Oxygen saturations in the high 80s or low 90s are common. Most patients in this group have mild to moderate elevation of PAP owing to elevated pulmonary blood flow. In most instances, PAP does not reach systemic levels.

1. Symptoms and signs

Patients may have mild cyanosis and tachypnea in the neonatal period and early infancy. Examination discloses dusky nail beds and mucous membranes, but overt cyanosis and digital clubbing are usually absent. An RV heave is palpable, and P₂ is increased. A systolic and diastolic murmur may be heard as a result of increased flow across the pulmonary and tricuspid valves, respectively.

2. Imaging

Chest radiography reveals cardiomegaly involving the right heart and pulmonary artery. Pulmonary vascular markings are increased.

3. Electrocardiography

ECG shows right-axis deviation and varying degrees of right atrial enlargement and RVH. A qR pattern is often seen over the right precordial leads.

4. Echocardiography

Demonstration by echocardiography of a discrete chamber posterior to the left atrium and an obligatory right-to-left atrial level shunt is strongly suggestive of the diagnosis. The availability of two-dimensional echocardiography plus color-flow Doppler has increased diagnostic accuracy such that diagnostic cardiac catheterization is rarely required.

B. With Obstructed Pulmonary Venous Return

This group includes many patients with infracardiac TAPVR and a few of the patients in whom venous drainage is into a systemic vein above the diaphragm. The pulmonary venous return is usually obstructed at the level of the ascending or descending vein that connects the confluence to the systemic veins to which it is draining. Obstruction can be caused from extravascular structures (such as the diaphragm), or by inherent stenosis within the ascending or descending vein.

1. Symptoms and signs

Infants usually present shortly after birth with severe cyanosis and respiratory distress and require early corrective surgery. Cardiac examination discloses a striking RV impulse. S₂ is markedly accentuated and single. Although there is often no murmur, sometimes, a systolic murmur is heard over the pulmonary area with radiation over the lung fields. Diastolic murmurs are uncommon.

2. Imaging

The heart is usually small and pulmonary venous congestion severe with associated air bronchograms. The chest radiographic appearance may lead to an erroneous diagnosis of severe lung disease. In less severe cases, the heart size may be normal or slightly enlarged with mild pulmonary venous congestion.

3. Electrocardiography

The ECG shows right-axis deviation, right atrial enlargement, and RVH.

4. Echocardiography

Echocardiography shows a small left atrium and LV, a dilated right heart with high RV pressure. For infracardiac TAPVR, appearance of a vessel lying parallel and anterior to the descending aorta and to the left of the IVC may represent the vein draining the confluence caudally toward the diaphragm. Color-flow Doppler echocardiography will demonstrate a right-to-left atrial level shunt and may reveal flow disturbance, commonly near the confluence or in the liver, where flow is obstructed.

5. Cardiac catheterization and angiocardiography

If echocardiography does not confirm the anatomy, cardiac catheterization and angiography demonstrate the site of entry of the anomalous veins, determine the degree of PH, and calculate PVR.

Treatment

Surgery is always required for TAPVR. If pulmonary venous return is obstructed, surgery must be performed immediately (obstructed TAPVR represents one of the few surgical emergencies in congenital heart disease). If early surgery is not required and the atrial septum is restrictive, a balloon atrial septostomy can be performed in newborns, to be followed shortly by less emergent surgical repair.

Course & Prognosis

Most children with TAPVR do well after surgery. However, some surgical survivors develop late stenosis of the pulmonary veins. Pulmonary vein stenosis is an intractable condition that is difficult to treat either with interventional catheterization or surgery and has a poor prognosis. A heart-lung transplant may be the only remaining option available to those with severe pulmonary vein stenosis. By avoiding direct suturing at the pulmonary venous ostia, the chance of recurrent stenosis at the anastomotic site is lessened. Unfortunately, any manipulation of the pulmonary veins increases the risk of stenosis.

TRUNCUS ARTERIOSUS

General Considerations

Truncus arteriosus accounts for less than 1% of congenital heart malformations. A single great artery arises from the heart, giving rise to the systemic, pulmonary, and coronary circulations. Truncus develops embryologically as a result of failure of the division of the common truncus arteriosus into the aorta and the pulmonary artery. A VSD is almost always present. The number of truncal valve leaflets varies from one to six, and the valve may be insufficient or stenotic.

Truncus arteriosus is divided into subtypes by the anatomy of the pulmonary circulation. A single main pulmonary artery may arise from the base of the trunk and gives rise to branch pulmonary arteries (type 1). Alternatively, the pulmonary arteries may arise separately from the common trunk, either in close association with one another (type 2) or widely separated (type 3). This lesion can occur in association with an interrupted aortic arch.

In patients with truncus, blood from both ventricles leaves the heart through a single exit. Thus, oxygen saturation in the pulmonary artery is equal to that in the systemic arteries. The degree of systemic arterial oxygen saturation depends on the ratio of pulmonary to systemic blood flow. If PVR is normal, the pulmonary blood flow is greater than the systemic blood flow and the saturation is relatively high. If PVR is elevated because of pulmonary vascular obstructive disease or small pulmonary arteries, pulmonary blood flow is reduced and oxygen saturation is low. The systolic pressures are systemic in both ventricles.

Clinical Findings

A. Symptoms and Signs

High pulmonary blood flow characterizes most patients with truncus arteriosus. These patients are usually minimally cyanotic and present in HF. Examination of the heart reveals a hyperactive precordium. A systolic thrill is common at the lower left sternal border. A loud early systolic ejection click is commonly heard. S₂ is single and accentuated. A loud holosystolic murmur is audible at the left lower sternal border. A diastolic flow murmur can often be heard at the apex due to increased pulmonary venous return crossing the mitral valve. An additional diastolic murmur of truncal insufficiency may be present.

Patients with decreased pulmonary blood flow are more profoundly cyanotic early. The most common manifestations are growth retardation, easy fatigability, and HF. The heart is not hyperactive. S₁ and S₂ are single and loud. A systolic murmur is heard at the lower left sternal border. No mitral flow murmur is heard, as pulmonary venous return is decreased. A loud systolic ejection click is commonly heard. In the current era, this lesion is often diagnosed by prenatal screening echocardiography.

B. Imaging

The common radiographic findings are cardiomegaly, absence of the main pulmonary artery segment, and a large aorta that has a right arch 30% of the time. The pulmonary vascular markings vary with the degree of pulmonary blood flow.

C. Electrocardiography

The axis is usually normal. RVH or combined ventricular hypertrophy is commonly present.

D. Echocardiography

Images generally show override of a single great artery (similar to ToF, but no second great artery arises directly from the heart). The origin of the pulmonary arteries and the degree of truncal valve abnormality can be defined. Color-flow Doppler can aid in the description of pulmonary flow and the function of the truncal valve, both of which are critical to management. Echocardiography is critical in identifying associated lesions, which will impact surgical planning, such as the presence of an interrupted aortic arch.

E. Angiocardiography

Cardiac catheterization is not routinely performed but may be of value in older infants in whom pulmonary vascular disease must be ruled out. The single most important angiogram would be from the truncal root, as both the origin of the pulmonary arteries and the amount of truncal insufficiency would be seen from one injection.

Treatment

Anticongestive measures are needed for patients with high pulmonary blood flow and congestive failure. Surgery is always required in this condition. Because of HF and the risk of development of pulmonary vascular disease, surgery is usually performed in the neonatal period or early infancy. The VSD is closed to allow LV egress to the truncal valve. The pulmonary artery (type 1) or arteries (types 2–3) are separated from the truncus as a block, and a valved conduit is fashioned from the RV to the pulmonary circulation.

Course & Prognosis

Children with a good surgical result generally do well. Outcome is also dependent to some degree on anatomy and integrity of the truncal valve, which becomes the “neoaortic” valve. Patients with a dysplastic valve may eventually require surgical repair or replacement of this valve. In addition, similar to patients with ToF, they eventually outgrow the RV-to-pulmonary artery conduit placed in infancy and require revision of the conduit in later childhood. The risk of early pulmonary vascular obstructive disease is high in the unrepaired patient and a decision to delay open-heart surgery beyond age 4–6 months is not wise even in stable patients.

The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) was formed in response to the Joint Council on Congenital Heart Disease (JCCHD) initiative to improve outcomes of children with heart disease. The mission of the NPC-QIC is to build a collaborative network of pediatric cardiologists and an associated database to serve as the foundation for improvement projects such as improving survival and quality of life in infants with HLHS. As outcomes improve and children with complex congenital heart disease are surviving into adulthood, subspecialty clinics addressing the needs of adults with repaired or palliated congenital heart disease are required to assess and advise patients regarding adult issues such as impact of pregnancy, risks of anticoagulation during pregnancy, and appropriate adult career choices. The Adult Congenital Pediatric Cardiology (ACPC) section of the American College of Cardiology has implemented quality metrics for various aspects of congenital heart disease, including ambulatory metrics for evaluation of chest pain, infection prevention, KD, ToF with genetic testing, evaluation of coarctation, TGA, preventative cardiology, and noninvasive imaging (https://cvquality.acc.org/initiatives/ACPC-Quality-Network).

RHEUMATIC FEVER

Rheumatic fever remains a major cause of morbidity and mortality in developing countries that suffer from poverty, overcrowding, and poor access to health care. Even in developed countries, rheumatic fever has not been entirely eradicated. The overall incidence in the United States is less than 1 per 100,000. Group A β-hemolytic streptococcal infection of the upper respiratory tract is the essential trigger in predisposed individuals. Only certain serotypes of group A streptococcus cause rheumatic fever. The latest attempts to define host susceptibility implicate immune response genes that are present in approximately 15% of the population. The immune response triggered by infection of the pharynx with group A streptococci consists of (1) sensitization of B lymphocytes by streptococcal antigens, (2) formation of anti-streptococcal antibody, (3) formation of immune complexes that cross-react with cardiac sarcolemma antigens, and (4) myocardial and valvular inflammatory response.

The peak age of risk in the United States is 5–15 years. The disease is slightly more common in girls and in African Americans. The annual death rate from rheumatic heart disease in school-aged children (whites and non-whites) recorded in the 1980s was less than 1 per 100,000.

Clinical Findings

Two major or one major and two minor manifestations (plus supporting evidence of streptococcal infection) based on the modified Jones criteria are needed for the diagnosis of acute rheumatic fever (Table 20–13). Except in cases of rheumatic fever manifesting solely as Sydenham chorea or long-standing carditis, there should be clear evidence of a streptococcal infection such as scarlet fever, a positive throat culture for group A β-hemolytic streptococcus, and increased antistreptolysin O or other streptococcal antibody titers. The antistreptolysin O titer is significantly higher in rheumatic fever than in uncomplicated streptococcal infections.

A. Carditis

Carditis is the most serious consequence of rheumatic fever and varies from minimal to life-threatening HF. The term carditis implies pancardiac inflammation, but it may be limited to valves, myocardium, or pericardium. Valvulitis is frequently seen, with the mitral valve most commonly affected. Mitral insufficiency is the most common valvular residua of acute rheumatic carditis. Mitral stenosis after acute rheumatic fever is rarely encountered until 5–10 years after the first episode. Thus, mitral stenosis is much more commonly seen in adults than in children.

An early decrescendo diastolic murmur consistent with aortic insufficiency is occasionally encountered as the sole valvular manifestation of rheumatic carditis. The aortic valve is the second most common valve affected in polyvalvular as well as in single-valve disease. The aortic valve is involved more often in males and in African Americans. Dominant aortic stenosis of rheumatic origin does not occur in pediatric patients. In one large study, the shortest length of time observed for a patient to develop dominant aortic stenosis secondary to rheumatic heart disease was 20 years.

B. Polyarthritis

The large joints (knees, hips, wrists, elbows, and shoulders) are most commonly involved, and the arthritis is typically migratory. Joint swelling and associated limitation of movement should be present. This is one of the more common major criteria, occurring in 80% of patients. Arthralgia alone is not a major criterion.

C. Sydenham Chorea

Sydenham chorea is characterized by involuntary and purposeless movements and is often associated with emotional lability. These symptoms become progressively worse and may be accompanied by ataxia and slurring of speech. Muscular weakness becomes apparent following the onset of the involuntary movements. Chorea is self-limiting, although it may last up to 3 months. Chorea may not be apparent for months to years after the acute episode of rheumatic fever.

D. Erythema Marginatum

A macular, serpiginous, erythematous rash with a sharply demarcated border appears primarily on the trunk and the extremities. The face is usually spared.

E. Subcutaneous Nodules

These usually occur only in severe cases, and then most commonly over the joints, scalp, and spinal column. The nodules vary from a few millimeters to 2 cm in diameter and are nontender and freely movable under the skin.

Treatment & Prophylaxis

A. Treatment of the Acute Episode

1. Anti-infective therapy

Eradication of the streptococcal infection is essential. Long-acting benzathine penicillin is the drug of choice. Depending on the age and weight of the patient, a single intramuscular injection of 0.6–1.2 million units is effective; alternatively, give penicillin V, 250–500 mg orally two to three times a day for 10 days, or amoxicillin, 50 mg/kg (maximum 1 g) once daily for 10 days. Narrow-spectrum cephalosporins, clindamycin, azithromycin, or clarithromycin are used in those allergic to penicillin.

2. Anti-inflammatory agents

A. ASPIRIN—Aspirin, 30–60 mg/kg/day, is given in four divided doses. This dose is usually sufficient to affect dramatic relief of arthritis and fever. Higher dosages carry a greater risk of side effects, and there are no proven short- or long-term benefits of high doses that produce salicylate blood levels of 20–30 mg/dL. The duration of therapy is tailored to meet the needs of the patient, but 2–6 weeks of therapy with reduction in dose toward the end of the course is usually sufficient. Other nonsteroidal anti-inflammatory agents used because of concerns about Reye syndrome are less effective than aspirin.

B. CORTICOSTEROIDS—There is no clear evidence to support the use of corticosteroids, but they are occasionally used for those with severe carditis.

3. Therapy in heart failure

Treatment for HF is based on symptoms and severity of valve involvement and cardiac dysfunction (see section Heart Failure).

4. Bed rest and ambulation

Bed rest is not required in most cases. Activity level should be commensurate with symptoms and children should be allowed to self-limit their activity level while affected. Most acute episodes of rheumatic fever are managed on an outpatient basis.

B. Treatment After the Acute Episode

1. Prevention

Prevention is critical, as patients who have had rheumatic fever are at greater risk of recurrence if future group A β-hemolytic streptococcal infections are inadequately treated. Follow-up visits are essential to reinforce the necessity for prophylaxis, with regular intramuscular long-acting benzathine penicillin injections preferred to oral medication due to better adherence. Long-term (possibly lifelong) prophylaxis is recommended for patients with residual rheumatic heart disease. More commonly, with no or transient cardiac involvement, 5–10 years of therapy or discontinuance in early adulthood (age 21) (whichever is longer) is an effective approach.

The following preventive regimens are in current use:

A. PENICILLIN G BENZATHINE—600,000 units for less than 27 kg, 1.2 million units for more than 27 kg intramuscularly every 4 weeks is the drug of choice.

B. PENICILLIN V—250 mg orally twice daily is much less effective than intramuscular penicillin benzathine G (5.5 vs 0.4 streptococcal infections per 100 patient-years).

C. SULFADIAZINE—500 mg for less than 27 kg and 1 g for more than 27 kg, once daily. Blood dyscrasias and lesser effectiveness in reducing streptococcal infections make this drug less satisfactory than penicillin benzathine G. This is the recommended regimen for penicillin-allergic patients.

D. ERYTHROMYCIN—250 mg orally twice a day may be given to patients who are allergic to both penicillin and sulfonamides. Azithromycin or clarithromycin may also be used.

2. Residual valvular damage

As described above, the mitral and aortic valves are most commonly affected by rheumatic fever and the severity of carditis is quite variable. In the most severe cases, cardiac failure or the need for a valve replacement can occur in the acute setting. In less severe cases, valve abnormalities can persist, requiring lifelong medical management and eventual valve replacement. Other patients fully recover without residual cardiac sequelae.

Although antibiotic prophylaxis to protect against endocarditis used to be recommended for those with residual valvular abnormalities, the criteria for prevention of IE were revised in 2007 and routine prophylaxis is recommended only if a prosthetic valve is in place.

KAWASAKI DISEASE

KD was first described in Japan in 1967 and was initially called mucocutaneous lymph node syndrome. The cause is unclear, and there is no specific diagnostic test. KD is the leading cause of acquired heart disease in children in the United States. Eighty percent of patients are younger than 5 years (median age at diagnosis is 2 years), and the male-to-female ratio is 1.5:1. Diagnostic criteria are fever for more than 5 days and at least four of the following features: (1) bilateral, painless, nonexudative conjunctivitis; (2) lip or oral cavity changes (eg, lip cracking and fissuring, strawberry tongue, and inflammation of the oral mucosa); (3) cervical lymphadenopathy greater than or equal to 1.5 cm in diameter and usually unilateral; (4) polymorphous exanthema; and (5) extremity changes (redness and swelling of the hands and feet with subsequent desquamation). In the presence of more than four principal clinical criteria, the diagnosis can be made with only 4 days of fever. Clinical features not part of the diagnostic criteria, but frequently associated with KD, are shown in Table 20–14.

The potential for cardiovascular complications is the most serious aspect of KD. Complications during the acute illness include myocarditis, pericarditis, valvular heart disease (usually mitral or aortic regurgitation), and coronary arteritis. Patients with fever for at least 5 days but fewer than four of the diagnostic features can be diagnosed with incomplete KD, especially if they have coronary artery abnormalities detected by echocardiography. Comprehensive recommendations regarding the evaluation for children with suspected incomplete KD were outlined in a 2017 Statement by the American Heart Association (see references at the end of this section).

Coronary artery lesions range from mild transient dilation of a coronary artery to large aneurysms. Aneurysms rarely form before day 10 of illness. Untreated patients have a 15%–25% risk of developing coronary aneurysms. Those at greatest risk for aneurysm formation are males, young infants (< 6 months), and those not treated with intravenous immunoglobulin (IVIG). Most coronary artery aneurysms resolve within 5 years of diagnosis; however, as aneurysms resolve, associated obstruction or stenosis (19% of all aneurysms) may develop, which may result in coronary ischemia. Giant aneurysms (> 8 mm) are less likely to resolve, and nearly 50% eventually become stenotic. Of additional concern, acute thrombosis of an aneurysm can occur, resulting in myocardial infarction that is fatal in approximately 20% of cases.

Treatment

Immediate management of KD includes IVIG and high-dose aspirin. This therapy is effective in decreasing the incidence of coronary artery dilation and aneurysm formation. The currently recommended regimen is 2 g/kg of IVIG administered over 10–12 hours and 80–100 mg/kg/day (some centers use 30–50 mg/kg/day) of aspirin in four divided doses. The duration of high-dose aspirin is institution-dependent: many centers reduce the dose once the patient is afebrile for 48–72 hours; others continue through 5 afebrile days or day 14 of the illness. Once high-dose aspirin is discontinued, low-dose aspirin (3–5 mg/kg/day) is given through the subacute phase of the illness (6–8 weeks) or until coronary artery abnormalities resolve. If fever recurs within 48–72 hours of the initial treatment course and no other source of the fever is detected, a second dose of IVIG is often recommended; however, the effectiveness of this approach has not been clearly demonstrated. Corticosteroids or other anti-inflammatory therapy (eg, infliximab) should be considered for patients with persistent fever despite one or two infusions of IVIG. Follow-up of patients with treated KD depends on the degree of coronary involvement (Table 20–15).

INFECTIVE ENDOCARDITIS

General Considerations

Bacterial or fungal infection of the endocardium of the heart is rare and usually occurs in the setting of a preexisting abnormality of the heart or great arteries. It may occur in a normal heart during septicemia or as a consequence of infected indwelling central catheters.

The frequency of infective endocarditis (IE) appears to be increasing for several reasons: (1) increased survival in children with congenital heart disease, (2) greater use of central venous catheters, and (3) increased use of prosthetic material and valves. Pediatric patients without preexisting heart disease are also at increased risk for IE because of (1) increased survival rates for children with immune deficiencies, (2) long-term use of indwelling lines in ill newborns and patients with chronic diseases, and (3) increased intravenous drug abuse.

Patients at greatest risk are children with unrepaired or palliated cyanotic heart disease (especially in the presence of an aorta to pulmonary shunt), those with implanted prosthetic material, and patients who have had a prior episode of IE. Common organisms causing IE are viridans streptococci (30%–40% of cases), Staphylococcus aureus (25%–30%), and fungal agents (about 5%).

Clinical Findings

A. History

The majority of patients with IE have a history of heart disease. There may or may not be an antecedent infection or surgical procedure (cardiac surgery, tooth extraction, tonsillectomy). Transient bacteremia occurs frequently during normal daily activities such as flossing or brushing teeth, using a toothpick and even when chewing food. Although dental and nonsterile surgical procedures also can result in transient bacteremias, these episodes are much less frequent for a given individual. This may be why a clear inciting event is often not identified in association with IE and also underlies the recent changes in guidelines for antibiotic prophylaxis to prevent IE (for details, see Wilson et al reference).

B. Symptoms, Signs, and Laboratory Findings

Although IE can present in a fulminant fashion with cardiovascular collapse, often it presents in an indolent manner with fever, malaise, and weight loss. Joint pain and vomiting are less common. On physical examination, there may be a new or changing murmur, splenomegaly, and hepatomegaly. Classic findings of Osler nodes (tender nodules, usually on the pulp of the fingers), Janeway lesions (nontender hemorrhagic macules on palms and soles), splinter hemorrhages, and Roth spots (retinal hemorrhage) are uncommonly noted in children. Laboratory findings include multiple positive blood cultures, elevated erythrocyte sedimentation rate or C-reactive protein, and hematuria. Transthoracic echocardiography can identify large vegetations in some patients, but transesophageal imaging has better sensitivity and may be necessary if the diagnosis remains in question.

Prevention

In 2007, the AHA revised criteria for patients requiring prophylaxis for IE (Table 20–16). Only the high-risk patients listed require antibiotics before dental work (tooth extraction or cleaning) and procedures involving the respiratory tract or infected skin or musculoskeletal structures. IE prophylaxis is not recommended for gastrointestinal or genitourinary procedures, body piercing, or tattooing. The impact of changes in the guideline in children is still uncertain.

Recommended prophylaxis is 50 mg/kg of oral amoxicillin for patients less than 40 kg and 2000 mg for those more than 40 kg. This dose is to be given 1 hour prior to procedure. If the patient is allergic to amoxicillin, alternative prophylactic antibiotics are recommended in the AHA guidelines.

Treatment

In general, appropriate antibiotic therapy should be initiated as soon as IE is suspected and several large volume blood cultures have been obtained via separate venipunctures. Therapy can be tailored once the pathogen and sensitivities are defined. Vancomycin or a β-lactam antibiotic, with or without gentamicin, for a 6-week course is the most common regimen. If HF occurs and progresses in the face of adequate antibiotic therapy, surgical excision of the infected area and prosthetic valve replacement must be considered.

Course & Prognosis

Factors associated with a poor outcome are delayed diagnosis, presence of prosthetic material, perioperative associated IE, and S aureus infection. Mortality for bacterial endocarditis in children ranges from 10% to 25%, with fungal infections having a much greater mortality (50% or more).

PERICARDITIS

General Considerations

Pericarditis is an inflammation of the pericardium and is commonly related to an infectious process. The most common cause of pericarditis in children is viral infection (eg, coxsackievirus, mumps, Epstein-Barr, adenovirus, influenza, and human immunodeficiency virus [HIV]). Purulent pericarditis results from bacterial infection (eg, pneumococci, streptococci, staphylococci, and Haemophilus influenzae) and is less common but potentially life threatening.

In some cases, pericardial disease occurs in association with a generalized process. Associations include rheumatic fever, rheumatoid arthritis, uremia, systemic lupus erythematosus, malignancy, and tuberculosis. Pericarditis after cardiac surgery (postpericardiotomy syndrome) is most commonly seen after surgical closure of an ASD. Postpericardiotomy syndrome appears to be autoimmune in nature with high titers of antiheart antibody and evidence of acute or reactivated viral illness. The syndrome is often self-limited and responds well to short courses of aspirin or corticosteroids.

Clinical Findings

A. Symptoms and Signs

Childhood pericarditis usually presents with sharp stabbing mid chest, shoulder, and neck pain made worse by deep inspiration or coughing, and decreased by sitting up and leaning forward. Shortness of breath and grunting respirations are common. Physical findings depend on the presence of fluid accumulation in the pericardial space (effusion). In the absence of significant accumulation, a characteristic scratchy, high-pitched friction rub may be heard. If the effusion is large, heart sounds are distant and muffled and a friction rub may not be present. In the absence of cardiac tamponade, the peripheral, venous, and arterial pulses are normal.

Cardiac tamponade occurs in association with a large effusion, or one that has rapidly accumulated. Tamponade is characterized by jugular venous distention, tachycardia, hepatomegaly, peripheral edema, and pulsus paradoxus, in which systolic blood pressure drops more than 10 mm Hg during inspiration. Decreased cardiac filling and subsequent decrease in cardiac output result in signs of right HF and the potential for cardiovascular collapse.

B. Imaging

In pericarditis with a significant pericardial effusion, the cardiac silhouette is enlarged. The cardiac silhouette can appear normal if the effusion has developed over an extremely short period of time.

C. Electrocardiography

The ST segments are commonly elevated in acute pericarditis and PR segment depression may be present. Low voltages or electrical alternans (alteration in QRS amplitude between beats) can be seen with large pericardial effusions.

D. Echocardiography

Serial echocardiography allows a direct, noninvasive estimate of the volume of pericardial fluid and its change over time. Cardiac tamponade is associated with compression of the atria or respiratory alteration of ventricular inflow demonstrated by Doppler imaging.

Treatment

Treatment depends on the cause of pericarditis and the size of the associated effusion. Viral pericarditis is usually self-limited, and symptoms can be improved with nonsteroidal anti-inflammatory therapy. Purulent pericarditis requires immediate evacuation of the fluid and appropriate antibiotic therapy. Cardiac tamponade from any cause must be treated by immediate removal of the fluid, usually via pericardiocentesis. Pericardiocentesis should also be considered if the underlying cause is unclear or identification of the pathogen is necessary for targeted therapy. In the setting of recurrent or persistent effusions, a surgical pericardiectomy or pericardial window may be necessary. Diuretics should be avoided in the patient with cardiac tamponade because they reduce ventricular preload and can exacerbate the degree of cardiac decompensation.

Prognosis

Prognosis depends to a great extent on the cause of pericardial disease. Constrictive pericarditis can develop following infectious pericarditis (especially if bacterial or tuberculous) and can be a difficult problem to manage. Cardiac tamponade will result in death unless the fluid is evacuated.

CARDIOMYOPATHY

There are five classified forms of cardiomyopathy in children: (1) dilated, (2) hypertrophic, (3) restrictive, (4) arrhythmogenic right ventricular dysplasia (ARVD), and (5) LV noncompaction. Discussion will be limited to the first three forms, which are the most common.

1. Dilated Cardiomyopathy

This most frequent of the childhood cardiomyopathies occurs with an annual incidence of 4–8 cases per 100,000 population in the United States and Europe. Although usually idiopathic, identifiable causes of dilated cardiomyopathy (DCM) include viral myocarditis, untreated tachyarrhythmias, left heart obstructive lesions, congenital abnormalities of the coronary arteries, medication toxicity (eg, anthracycline), and genetic (eg, dystrophin gene defects, sarcomeric mutations) and metabolic diseases (inborn errors of fatty acid oxidation and mitochondrial oxidative phosphorylation defects). Genetic causes are being discovered at an increasing rate with commercial testing now available for some of the more common genes.

Clinical Findings

A. Signs and Symptoms

As myocardial function fails and the heart dilates, cardiac output falls, and affected children develop decreased exercise tolerance, failure to thrive, diaphoresis, and tachypnea. As the heart continues to deteriorate, congestive signs such as hepatomegaly and rales develop, and a prominent gallop can be appreciated on examination. The initial diagnosis in a previously healthy child can be difficult, as presenting symptoms can resemble a viral respiratory infection, pneumonia, or asthma.

B. Imaging

Chest radiograph shows generalized cardiomegaly with or without pulmonary venous congestion.

C. Electrocardiography

Sinus tachycardia with ST-T segment changes is commonly seen on ECG. The criteria for RVH and LVH may also be met, and the QT interval may be prolonged. Evaluation for the presence of supraventricular arrhythmias on ECG is critical, as this is one of the few treatable and reversible causes of DCM in children.

D. Echocardiography

The echocardiogram shows LV and left atrial enlargement with decreased LV-shortening fraction and ejection fraction. The calculated end-diastolic and end-systolic dimensions are increased, and mitral insufficiency is commonly seen. A careful evaluation for evidence of structural abnormalities (especially coronary artery anomalies or left heart obstructive lesions) must be performed, especially in infant patients.

E. Other Testing

Cardiac catheterization is useful to evaluate hemodynamic status and coronary artery anatomy. Endomyocardial biopsies can aid in diagnosis. Biopsy specimens may show inflammation consistent with acute myocarditis, abnormal myocyte architecture, and myocardial fibrosis. Electron micrographs may reveal evidence of mitochondrial or other metabolic disorders. Polymerase chain reaction (PCR) testing may be performed on biopsied specimens to detect viral genome products in infectious myocarditis. Cardiopulmonary stress testing is useful for measuring response to medical therapy and as an objective assessment of the cardiac limitations on exercise.

Treatment & Prognosis

Outpatient management of pediatric DCM usually entails combinations of afterload-reducing agents and diuretics (see section Heart Failure). In 2007, Shaddy et al published the results of a multicenter, placebo-controlled, double-blind trial of carvedilol in children with HF. Children did not receive the same beneficial effects of β-blocker therapy as adults with HF, possibly due to the heterogenous nature of HF in children and increasing evidence that there are inherent differences in pediatric and adult HF. Aspirin or warfarin may be used to prevent thrombus formation in the dilated and poorly contractile cardiac chambers. Arrhythmias are more common in dilated hearts and antiarrhymthmic therapy is sometimes necessary. Despite widespread use of internal defibrillators in the adult population, the technical difficulty of implanting internal defibrillators, the risk of adverse events (eg, high frequency of inappropriate discharge, vascular obstruction), and the low incidence of sudden cardiac death (SCD) in children limit their use.

Therapy of the underlying cause of cardiomyopathy is always indicated if possible. Unfortunately despite complete evaluation, a diagnosis is discovered in less than 30% of patients with DCM. If medical management is unsuccessful, cardiac transplantation is considered.

2. Hypertrophic Cardiomyopathy

The most common cause of hypertrophic cardiomyopathy (HCM) is familial HCM, which is found in 1 in 500 individuals. HCM is the leading cause of SCD in young persons. The most common presentation is in an older child, adolescent, or adult, although it may occur in neonates. Causes of nonfamilial HCM in neonates and young children include glycogen storage disease, Noonan syndrome (including related syndromes such as LEOPARD and Costello syndrome), Friedreich ataxia, maternal gestational diabetes, mitochondrial disorders, and other metabolic disorders.

A. Familial Hypertrophic Cardiomyopathy

In the familial form, HCM is most commonly caused by a mutation in one of the several genes that encode proteins of the cardiac sarcomere (β-myosin heavy chain, cardiac troponin T or I, α-tropomyosin, and myosin-binding protein C).

1. Clinical findings

Patients may be asymptomatic despite having significant hypertrophy, or may present with symptoms of inadequate coronary perfusion or HF such as angina, syncope, palpitations, or exercise intolerance. Patients may experience SCD as their initial presentation, often precipitated by sporting activities. Although the cardiac examination may be normal on presentation, some patients develop a left precordial bulge with a diffuse point of maximal impulse. An LV heave or an S₄ gallop may be present. If outflow tract obstruction exists, a systolic ejection murmur will be audible. A murmur may not be audible at rest but may be provoked with exercise or positional maneuvers that decrease LV volume (standing), thereby increasing the outflow tract obstruction.

A. ECHOCARDIOGRAPHY—The diagnosis of HCM is usually made by echocardiography and in most familial cases demonstrates asymmetrical septal hypertrophy. Young patients with metabolic or other nonfamilial causes are more likely to have concentric hypertrophy. Systolic anterior motion of the mitral valve leaflet may occur and contribute to LV outflow tract obstruction. The mitral valve leaflet may become distorted and result in mitral insufficiency. LV outflow tract obstruction may be present at rest or provoked with monitored exercise. Systolic function is most often hypercontractile in young children but may deteriorate over time, resulting in poor contractility and LV dilation. Diastolic function is almost always abnormal.

B. ELECTROCARDIOGRAPHY—The ECG may be normal but more typically demonstrates deep Q waves in the inferolateral leads (II, III, aVF, V₅, and V₆) secondary to the increased mass of the hypertrophied septum. ST-segment abnormalities may be seen in the same leads. Age-dependent criteria for LVH are often present as criteria for left atrial enlargement.

C. OTHER TESTING—Cardiopulmonary stress testing is valuable to evaluate for provocable LV outflow tract obstruction, ischemia, and arrhythmias, and to determine prognosis. Extreme LVH and a blunted blood pressure response to exercise have both been associated with increased mortality in children. Cardiac MRI is useful for defining areas of myocardial fibrosis or scarring. Patients are at risk for myocardial ischemia, possibly as a result of systolic compression of the intramyocardial septal perforators, myocardial bridging of epicardial coronary arteries, or an imbalance of coronary artery supply and demand due to the presence of massive myocardial hypertrophy.

D. CARDIAC CATHETERIZATION—Cardiac catheterization may be performed in patients with HCM who have angina, syncope, resuscitated sudden death, or a worrisome stress test. Hemodynamic findings include elevated left atrial pressure secondary to impaired diastolic filling. If midcavitary LV outflow tract obstruction is present, an associated pressure gradient will be evident. Provocation of LV outflow tract obstruction with either rapid atrial pacing or isoproterenol may be sought, but this is not commonly done in children. Angiography demonstrates a “ballerina slipper” configuration of the LV secondary to the midcavitary LV obliteration during systole. Although uncommonly done in the current era, myocardial biopsy demonstrates myofiber disarray.

2. Treatment and prognosis

Treatment varies depending on symptoms and phenotype. Affected patients are restricted from competitive athletics and isometric exercise due to associated risk of SCD. Patients with resting or latent LV outflow tract obstruction may be treated with β-blockers, verapamil, or disopyramide with variable success in alleviating obstruction. Patients with severe symptoms despite medical therapy and an LV outflow tract gradient may require additional intervention. Surgical myectomy with resection of part of the hypertrophied septum has been used in symptomatic patients with good results. At the time of myectomy, the mitral valve may require repair or replacement in patients with a long history of systolic anterior motion of the mitral valve. Ethanol ablation is used in adults with HCM and LV outflow tract obstruction. This procedure involves selective infiltration of ethanol in a coronary septal artery branch to induce a small targeted myocardial infarction. This leads to a reduction in septal size and improvement of obstruction. The long-term effects of this procedure are unknown, and it is not commonly employed in children. Dual-chamber pacing to relieve obstruction has been used in children, but data to support its use are lacking. Risk stratification with respect to sudden death is important in HCM. Consideration for placement of internal defibrillators in adult patients are based on the known risk factors for SCD: severe hypertrophy (> 3 cm septal thickness in adults), documented ventricular arrhythmias, syncope, abnormal blood pressure response to exercise, resuscitated sudden death, or a strong family history of HCM with associated sudden death. The criteria for defibrillator placement in children are not as well defined.

B. Glycogen Storage Disease of the Heart

There are at least 10 types of glycogen storage disease. The type that primarily involves the heart is Pompe disease (GSD IIa) in which acid maltase, necessary for hydrolysis of the outer branches of glycogen, is absent. There is marked deposition of glycogen within the myocardium. Affected infants are well at birth, but symptoms of growth and developmental delay, feeding problems, and cardiac failure occur by the sixth month of life. Physical examination reveals generalized muscular weakness, a large tongue, and cardiomegaly without significant heart murmurs. Chest radiographs reveal cardiomegaly with or without pulmonary venous congestion. The ECG shows a short PR interval and LVH with ST depression and T-wave inversion over the left precordial leads. Echocardiography shows severe concentric LVH. Although historically children with Pompe disease usually died before age 1 year, recent enzyme replacement clinical trials have shown some promise in reversing hypertrophy and preserving cardiac function. Death may be sudden or result from progressive HF.

3. Restrictive Cardiomyopathy

Restrictive cardiomyopathy is a rare entity in the pediatric population, accounting for less than 5% of all cases of cardiomyopathy. The cause is usually idiopathic but can be familial or secondary to an infiltrative process (eg, amyloidosis).

Clinical Findings

Patients present with signs of congestive HF as a consequence of diastolic dysfunction in the setting of preserved systolic function. The LV is more severely affected than the RV in restrictive cardiomyopathy, but the RV is also affected in most cases resulting in signs and symptoms consistent with biventricular congestion. Patients often present with exercise intolerance, fatigue, chest pain, and orthopnea. Physical examination is remarkable for a prominent S₄ and jugular venous distention.

A. Electrocardiography

ECG demonstrates marked right and left atrial enlargement with normal ventricular voltages. ST-T–wave abnormalities including a prolonged QTc interval may be present.

B. Echocardiography

The diagnosis is confirmed echocardiographically by the presence of normal-sized ventricles with normal systolic function and massively dilated atria. Cardiac MRI is useful in ruling out pericardial abnormalities (restrictive or constrictive pericarditis) and infiltrative disorders.

Treatment & Prognosis

Anticongestive therapy is used for symptomatic relief. The risk of sudden death in restrictive cardiomyopathy and the propensity for rapid progression of irreversible PH warrant close follow-up with early consideration of cardiac transplantation.

MYOCARDITIS

The most common causes of viral myocarditis are adenoviruses, coxsackie A and B viruses, echoviruses, parvovirus, cytomegalovirus, and influenza A virus. HIV can also cause myocarditis. The ability to identify the pathogen has been enhanced by PCR technology, which replicates identifiable segments of the viral genome from the myocardium of affected children.

Clinical Findings

A. Symptoms and Signs

There are two major clinical patterns. In the first, sudden-onset HF occurs in an infant or child who was relatively healthy in the hours to days previously. This malignant form of the disease is usually secondary to overwhelming viremia with tissue invasion in multiple organ systems including the heart. In the second pattern, the onset of cardiac symptoms is gradual, and there may be a history of upper respiratory tract infection or gastroenteritis in the previous month. This more insidious form may have a late postinfectious or autoimmune component. Acute and chronic presentations occur at any age and with all types of myocarditis.

The signs of HF are variable, but in a decompensated patient with fulminant myocarditis, they include pale gray skin; rapid, weak, and thready pulses; and breathlessness. In those with a more subacute presentation signs include increased work of breathing such as orthopnea, difficulty with feeding in infants, exercise intolerance and edema of the face and extremities. The patient is usually tachycardic and heart sounds may be muffled and distant; an S₃ or S₄ gallop (or both) are common. Murmurs are usually absent, although a murmur of tricuspid or mitral insufficiency may be heard. Moist rales are usually present at both lung bases. The liver is enlarged and frequently tender.

B. Imaging

Generalized cardiomegaly is seen on radiographs along with moderate to marked pulmonary venous congestion.

C. Electrocardiography

The ECG is variable. Classically, there is low-voltage QRS in all frontal and precordial leads with ST-segment depression and inversion of T waves in leads I, III, and aVF (and in the left precordial leads during the acute stage). Dysrhythmias are common, and AV and intraventricular conduction disturbances may be present.

D. Echocardiography

Echocardiography demonstrates four-chamber dilation with poor ventricular function and AV valve regurgitation. A pericardial effusion may be present. Patients with a more acute presentation may have less ventricular dilation than those with a longer history of HF-related symptoms.

E. Myocardial Biopsy