Congenital Heart Disease

Fetal-to-Postnatal Transition

The hemodynamic state of the fetus differs significantly from that of the newborn. In the fetus, a relatively low systemic vascular resistance exists because of the presence of the placenta, and the pulmonary vasculature maintains a high resistance. Central shunts exist for nutrient-rich blood from the placenta to be delivered to the fetal circulation both within the heart (foramen ovale) and on the arterial side of the circulation (ductus arteriosus).

The ductus venosus serves as a flow regulator between the umbilical vein and the inferior vena cava (IVC), largely bypassing the hepatic and portal venous systems. Based on studies in fetal sheep, less than one-half of the umbilical venous return enters the left lobe of the liver and reaches the ductus venosus near its insertion into the IVC, returning as relatively nutrient-rich blood. The lateral position of the IVC within the right atrium results in streaming of placental blood across the foramen ovale and into the left atrium. The most desaturated blood to return to the right atrium comes from the coronary sinus, which combines with the venous return from the superior vena cava (SVC) and is directed across the tricuspid valve into the right ventricle. The nutrient-rich blood deriving from the umbilical vein, which has crossed the foramen ovale to enter the left side of the heart, predominantly supplies the heart and brain. Output from the right ventricle supplies the lungs and flows right-to-left through the ductus arteriosus to supply the remainder of the body. In the fetus, the presence of the ductus arteriosus, which is nonrestrictive, results in both ventricles being subjected to a comparable afterload. Compared with the postnatal heart, this results in an increase in right ventricular workload and some restriction to filling of the right ventricle, thus the right ventricle carries the primary workload of the fetal heart. The ventricles exist in parallel in the fetal heart and output is described as combined cardiac output.

At birth, several important transitions take place that allow the fetus to adapt to extrauterine life. First, the gradual decline in pulmonary vascular resistance (PVR) that was occurring during the last trimester of pregnancy undergoes an abrupt drop with the first breath taken by the newborn ( Fig. 50.1 ). This decline in PVR results in a more than 20-fold increase in pulmonary blood flow and reversal of flow (left-to-right) in the ductus arteriosus before its closure. Second, the shunts present in the fetus undergo closure such that blood flow transitions from parallel to flow in series through the body. The ductus venosus closes largely because of lack of flow following separation of the placenta, although some contractile elements may be present in the vessel wall. The foramen ovale becomes occluded as the flap of the septum primum abuts the septum secundum following the increased pulmonary blood flow that increases filling of the left atrium. Small residual left-to-right shunts at the foramen ovale may persist and in 20% to 30% of the population a patent foramen ovale may exist throughout life (see “Atrial Septal Defects” later in the chapter). Closure of the ductus arteriosus is mediated by decreased blood flow and increased arterial oxygen tension; in contrast, patency of the ductus can usually be maintained by exogenous prostaglandin administration. The third important transition at birth is an increase in the combined ventricular output as the metabolic demands of the body increase at birth.

The dramatic hemodynamic changes that occur at birth continue to evolve over the next few months. There is a continued decline in PVR during the first 6 to 8 weeks after birth. In addition, the right ventricle remodels to a thinner and more compliant ventricle and the left ventricle becomes the dominant ventricle of the heart.

Nomenclature

Differing nomenclatures have evolved to define cardiac anatomy and spatial relationships. While the brief summary of nomenclature that is given here is based on the segmental approach of Anderson et al. the embryologic approach of Van Praagh is equally valid and used by several institutions.

The segmental approach to describing cardiac anatomy includes:

• 1.

  Cardiac position

• 2.

  Visceral sidedness

• 3.

  Systemic and pulmonary venous connections

• 4.

  Atrial sidedness and their connections

• 5.

  Atrioventricular (AV) valves

• 6.

  Ventricular relationship

• 7.

  Ventriculoarterial connections

• 8.

  Great vessel number and position

The description of cardiac position in the chest can be separated into where the heart is located and the direction in which the apex of the heart is pointed. Normally, the heart is in the left chest with the apex pointed to the left. Dextro- (right) or meso- (midline) position of the heart can occur with decreased right lung volume, severe scoliosis, or an elevated left diaphragm. A preliminary assessment of the position of the heart in the chest can be determined by a chest x-ray. The normal leftward-pointing apex of the heart (levocardia) can vary to mesocardia (apex pointing midline) or dextrocardia (apex pointing rightward). The orientation of the apex of the heart is defined by echocardiography or cross-sectional imaging.

Visceral sidedness is often defined separately for the abdominal organs, the cardiac structures, and the lungs, although they frequently follow one another. Sidedness is referred to as solitus (normal), inversus (mirror image), or ambiguous (isomerism or indeterminate). In the latter situation, effort is made to define whether the organs that appear on both sides are right-sided (liver, right atrium, and trilobed lung) or left-sided (stomach/spleen, left atrium, bilobed lung) structures since this can have prognostic and therapeutic importance. For instance, patients with bilateral right-sidedness typically lack a spleen and require lifelong antibiotic prophylaxis for encapsulated organisms. Additionally, these patients can have malrotation of the intestines and are at risk for volvulus.

Venous connections of the superior and inferior venous systems must also be delineated. The usual connection of the SVC to the right atrium may also be accompanied by a persistent left SVC to the coronary sinus, with or without a bridging brachiocephalic vein. The IVC is derived from various embryologic vessels. Interruption of the IVC can occur due to failure of fusion of any of the embryological parts. Lower extremity blood flow is consequentially routed to the SVC through the azygous or hemiazygous systems. Various pulmonary venous connections are described below.

Atria can be solitus with the morphologic right atrium on the right (normal), inversus, mirror image, common, or indeterminate. The right atrium is typically identified by the presence of a coronary sinus, the presence of the crista terminalis (the muscular ridge separating the muscular and smooth portions of the right atrium, the large sailed-shaped appendage, and the coarse pectinate muscles of the free wall). The left atrium is characterized by its smooth walls and narrow, finger-shaped appendage. Atrial morphology can be discerned by several imaging modalities such as echocardiography, cross-sectional imaging such as magnetic resonance imaging and computed tomography and more historically angiography. When the morphologic right atrium connects to the morphologic right ventricle (and similarly on the left), the connection is concordant . A discordant connection occurs when the morphologic right atrium connects to the morphologic left ventricle as in corrected transposition of the great arteries (TGA). When both atria connect to one ventricle (as in double inlet left ventricle) or a single ventricle, the type of connection is referred to as univentricular . An ambiguous connection occurs in cases of atrial isomerism.

The AV valves generally remain committed to their respective ventricles throughout embryology. As such, the tricuspid valve, when present, connects to the morphologic right ventricle, and the mitral valve connects to the morphologic left ventricle. The tricuspid valve has three leaflets and is distinguished from the mitral valve by the septal attachments of its papillary muscles and the slight inferior position of the septal leaflet of the tricuspid valve relative to the anterior leaflet of the mitral valve. When the AV valves fail to undergo septation, a common AV valve is found, as in children with a complete AV septal defect. The position of the AV valves and their chordal attachments are used to define whether the valves are malaligned or straddling. A malaligned AV valve is not completely positioned over its respective ventricle, which is sometimes referred to as overriding . If the chordal attachments of an AV valve cross the septum and connect to the other ventricle, an AV valve is referred to as straddling.

The morphology of the ventricles, the associated AV valve, and the outflow portion of the ventricle can generally be used to identify the right and left ventricles. The right ventricle, besides being associated with the tricuspid valve, is more heavily trabeculated at its apex and anterior free wall than the left ventricle. The right ventricle is described as tripartite and consists of an inflow, body, and outflow. The inflow includes the tricuspid valve, the papillary muscles which are responsible for anchoring the valve leaflets, and the chordae tendineae, which are the fibrous cords anchoring the tricuspid valve to the papillary muscles. The body includes the trabeculated muscular portion of the ventricle and the outflow which extends toward the pulmonary valve in the form of a tract. Along this outflow tract is the infundibulum or conus, which is a muscular separation between the tricuspid and semilunar valves. The left ventricle is more smooth-walled with finer trabeculations at its apex than the right ventricle, and in normal anatomy demonstrates fibrous continuity between the mitral and aortic valves. When the ventricular morphology is uncertain, the ventricles are said to be indeterminate. A common ventricle is defined by virtual absence of the interventricular septum.

The great vessels are largely defined by their branching pattern. The pulmonary artery bifurcates shortly after exiting the heart into the right and left pulmonary arteries that undergo subsequent branching to supply the segments of the lung. The right pulmonary artery is positioned anterior to the right upper bronchus while the left pulmonary artery is posterior to the left upper bronchus. The pulmonary arteries typically follow the situs of the lungs such that mirror image pulmonary artery branching is seen in situs inversus, bilateral branch pulmonary arteries anterior to the upper bronchus are seen in right isomerism, and branch pulmonary arteries posterior to the upper bronchus are seen in left isomerism. The aorta is normally left sided, and courses over the left mainstem bronchus giving rise to three head and neck arterial branches. A right aortic arch crosses over the right mainstem bronchus before crossing back to the left side of the spine in the thorax and can have several different branching patterns. While the aorta is typically posterior and rightward to the main pulmonary artery, the relative position of the vessels can vary greatly. Most commonly, in d-transposition of the great arteries, the aorta is anterior and rightward to the main pulmonary artery. In situations where only a single semilunar valve is present, a truncus arteriosus (or common truncal artery) is found that gives rise to both the aorta and pulmonary artery.

The ventriculoarterial connections are said to be concordant when the right ventricle connects to the pulmonary artery and the left ventricle gives rise to the aorta. The ventriculoarterial connection is discordant when the opposite occurs. The ventriculoarterial connection can also be double, single, or common. If both great arteries arise from one ventricle, a double outlet occurs. The definition of a double outlet connection is somewhat controversial. For example, in the case of double outlet right ventricle (DORV) with normally related great vessels, some clinicians have proposed basing the definition on whether greater than 50% of the aorta overrides the right ventricle, while others define the double outlet on whether a subaortic conus exists that results in mitral–aortic discontinuity. From a patient management perspective, both situations are relevant for either placement of the ventricular septal defect (VSD) patch or the potential for development of subaortic obstruction, respectively. A single outlet occurs when severe pulmonary hypoplasia occurs such that no main pulmonary artery segment is present. A common outlet occurs in truncus arteriosus.

Clinical Evaluation of the Newborn

Even with the technologic advances in prenatal and postnatal echocardiography and genetic testing, a careful history and physical examination are needed in every newborn with suspected congenital heart disease (CHD). Birth history, including complications during pregnancy, labor, and delivery, is important to document. Often the child with cyanosis because of structural heart disease has an unremarkable birth history. A difficult labor or delivery may point toward noncardiac causes of cyanosis such as persistent fetal circulation, infection, or pneumothorax. For the child with poor systemic perfusion, a history of premature rupture of membranes or maternal fever may suggest sepsis as a cause for the diminished cardiac function. Hematologic abnormalities that may cause cardiovascular dysfunction in the neonate, such as polycythemia or anemia, may be suggested by a history of placental abruption or twin–twin transfusion.

Family history is critical to review with the biologic parents. There is a genetic basis for a growing number of congenital heart defects (see later). A sibling with CHD more than doubles the likelihood of future children having CHD. A history of CHD in either of the parents also increases the chance of developing a congenital heart lesion.

Physical examination of the newborn should initially include a general assessment looking for dysmorphic features and the degree of distress of the infant. The child with cardiac obstructive physiology may have shallow, rapid respirations with intercostal and suprasternal retractions. Cyanosis may or may not be seen depending on the degree of hemoglobin desaturation (roughly 5 g of hemoglobin must be desaturated to be clinically evident). Vital signs, including four extremity blood pressures, should be determined along with preductal and postductal oxygen saturation measurement. Palpation of the precordium may identify an overactive or displaced cardiac impulse or the sensation of a thrill caused by turbulent flow. Palpation of the abdomen for a liver edge or spleen tip can often provide an indication of volume overload or neonatal infection. Assessment of femoral and upper extremity pulses is essential. Simultaneous palpation of the right branchial and right femoral pulses allows assessment of comparable timing and intensity of the pulsations. Perfusion and capillary refill of the extremities are also important to determine.

Auscultation is often challenging in the sick neonate. However, characterizing the presence, timing, intensity, position, and radiation of murmurs that are present may provide a clue to the underlying diagnosis. In the tachypneic and tachycardic child, it is critical to listen over the head and liver for a continuous murmur that may indicate an arteriovenous malformation (AVM). The presence of a click or gallop over the precordium may indicate valvar disease or cardiac failure. Assessment of the second heart sound is particularly important. It has been suggested that the presence of physiologic splitting of the second heart sound nearly always suggests a structurally normal heart.

Signs of CHF in the newborn may be subtle and include resting tachypnea (with no periodic variation), sinus tachycardia, and an enlarged liver. Tachypnea may be accompanied by nasal flaring and intercostal and subcostal retractions, particularly in situations where elevated pulmonary venous pressures are present. Grunting respirations are a particularly concerning sign in a newborn and often accompany severe heart failure and decreased systemic perfusion.

Because many infants with CHD are asymptomatic in the newborn period and have a normal physical examination and because routine prenatal ultrasound does not detect all defects, it has been recommended that pulse oximetry screening should be added to the routine newborn screening panel. The screen specifically targets critical congenital heart defects or those that usually require an intervention in the first month of life and can lead to death or significant morbidity if not diagnosed in a timely manner. Since this recommendation, there have been several studies focusing on the feasibility, implementation, and impact of the screen.

Laboratory Assessment of the Neonate

As mentioned previously, initial laboratory assessment should include measurement of preductal and postductal oxygen saturations in the right hand and foot, respectively, in a left aortic arch with normal branching. Values less than 93% are considered abnormal. The oxygen challenge test is performed by increasing the inspired oxygen concentration to 100% for at least 5 minutes. Oxygen saturation values that increase into the normal range may be useful to distinguish an admixture cyanotic heart lesion from lung disease, although this test does not discriminate with 100% accuracy. History and physical examination should be included and guide the need for further evaluation. A decrease in postductal oxygen saturations compared with preductal values suggests right-to-left shunting because of an increase in PVR. The unusual situation in which the preductal saturation reading is less than the postductal reading occurs when TGA is combined with pulmonary hypertension and a patent ductus arteriosus (PDA).

An electrocardiogram (ECG) should be obtained in the initial evaluation of the newborn with suspected CHD, although in the absence of an arrhythmia, it rarely provides a specific diagnosis. The neonatal ECG demonstrates prominent rightward forces and may have an upright T wave in the right precordial leads in the first few days after birth, and thus it may not be diagnostic of right ventricular hypertrophy. Age-dependent standards are available and should be referred to when evaluating the ECG ( Table 50.1 ). Certain lesions may have distinctive findings on ECG such as extreme right axis deviation and Q waves in leads I and aVL (complete AV septal defect), preexcitation and right atrial enlargement (Ebstein anomaly), and Q waves in leads V1–V3 (congenitally corrected TGA).

A chest x-ray should also be obtained in every newborn that is evaluated for CHD. The chest x-ray may help to determine the heart size, shape, and border contours as well as pulmonary vascular markings. A prominent thymic shadow in the newborn may make identification of classic chest x-ray findings difficult, such as the “boot-shaped” heart in tetralogy of Fallot (TOF), the “egg on a string” in transposition, and the “snowman” appearance in supracardiac total anomalous pulmonary venous return (TAPVR), although the massively increased heart size typically found with Ebstein anomaly will not be missed. An absent thymic shadow may suggest DiGeorge syndrome (22q11 deletion), although genetic testing is still required. Increases in pulmonary vascular markings typically found in left-to-right shunt lesions may not be immediately apparent in the newborn because of the relatively high PVR and may take days or weeks to become apparent. Often, decreased pulmonary vascular markings in lesions with diminished pulmonary blood flow, such as tricuspid or pulmonary atresia, will be apparent in the newborn period. Presence of a PDA, however, will improve pulmonary blood flow in these lesions. Echocardiography is truly the mainstay in the diagnosis of CHD in the neonate. The suspicion of CHD warrants immediate consultation with a pediatric cardiologist and evaluation of the neonate by echocardiography.

Genetics and Congenital Heart Disease

About 30% of children with a chromosomal abnormality will have congenital heart disease. There are an estimated 400 genes associated with CHD, and the understanding of the genetic basis of CHD is progressing at a rapid pace. Blue et al. depicted the evolution of genetic testing and its impact on elucidating relevant genetic associations with CHD over the past several decades ( Fig. 50.2 ).

Cardiogenesis is driven by a complex interplay between several processes including but not limited to transcription factors, signaling pathways, chromatin modifiers, and protein development. Thus, the genetic pathways that drive cardiac development are multifactorial. Disruptions in genetic pathways can include point mutations, aneuploidy, and copy number variations all occurring as de novo mutations or due to Mendelian inheritance with varying penetrance. We will briefly review some of these genetic variations and associated congenital heart defects.

Point mutations are an alteration of a single nucleotide sequence in a particular gene. This generally results in one of three outcomes. The result can be inconsequential because the alteration is coding for the same amino acid. In contrast, a missense mutation can occur if the new codon corresponds to a different amino acid. Lastly, a nonsense mutation can occur resulting in a stop codon terminating the gene transcription altogether. An estimated 2% of CHDs are due to point mutations. For example, HAND 1 and 2 are transcription factors that play a role in regulating ventricular looping and development. A loss of function mutation in HAND 1 can result in an arrest at the ventricular looping stage of cardiogenesis and the mutation has been identified in patients with hypoplastic left heart syndrome (HLHS), right heart hypoplasia, and double outlet right ventricle (DORV).

Copy number variants are the deletion or duplication of specific regions of DNA usually involving a significant number of base pairs. These are estimated to cause 10% to 15% of CHD. An example of this type of mutation is 22q11 deletion, also known as DiGeorge syndrome or velocardiofacial syndrome which is commonly associated with conotruncal anomalies such as interrupted aortic arch (IAA), TOF, and truncus arteriosus (TA). 22q11 deletion alters the expression of TBX1, a key transcription factor in the development of the pharyngeal pouches and arches. In addition to CHD, the manifestations of the syndrome, although phenotypically heterogenous, can include parathyroid gland absence leading to hypocalcemia, thymic aplasia, neurodevelopmental delays, and characteristic facial features.

Aneuploidy is the loss or gain of an entire chromosome or chromosomal segment. For example trisomy 13, 18, and 21 are all additions of chromosomes 13, 18, and 21. These defects are associated with cardiac disease 80% to 100% of the time in trisomy 13 and 18 and 40% to 55% of the time in trisomy 21. Turner syndrome is the loss of an X chromosome. CHD can occur in up to 50% of patients with Turner, and lesions are commonly associated with the left side of the heart such as bicuspid aortic valve and coarctation of the aorta. Wolf-Hirschhorn syndrome is the partial deletion of the short arm of chromosome 4 and is associated with CHD about 50% of the time. Common lesions associated with Wolf-Hirschhorn syndrome include atrial septal defects, ventricular septal defects, and pulmonary stenosis.

Despite advances in the understanding of the genetic basis of CHD, the genetic basis of more than half of children with CHD is not known. It is likely that altered interactions with noncoding regions of the genome impact the degree to which genes that regulate cardiac development are expressed. There may also be gene–environment interactions, yet to be defined, which impact cardiac development.

The Genetic Work-Up of Congenital Heart Disease

A child with suspected CHD should be carefully evaluated for dysmorphic features that may indicate an associated syndrome. Similarly, newborns with suspected genetic syndromes should be screened for congenital heart disease. Fig. 50.3 demonstrates a genetic screening algorithm. Genetic testing should be performed not only in patients with suspected CHD but also in the setting of suggestive physical features, family history, or positive prenatal genetic testing. Fluorescent in situ hybridization (FISH) is the use of fluorescent probes to map specific deoxyribonucleic acid (DNA) sequences and is the test of choice for identifying 22q11, while single-gene disorders such as Noonan syndrome require whole-exome sequencing.

Genetic testing is not only useful for prognostic information for the individual patient but plays a significant role in pre- and postnatal family counseling and future family planning. Referral to a consulting genetics team allows for the consideration of services available to the infant, screening of additional family members, and discussion of the risks to future pregnancies.

Heart Transplantation

Although many congenital heart defects can be corrected or palliated, cardiac transplantation must be considered in instances where there is intrinsic cardiac dysfunction such as cardiomyopathy or in circumstances where surgical repair has not sufficiently corrected a child’s hemodynamics. In those cases, cardiac transplantation may be the only therapeutic option.

The first heart transplant in an infant was reported in 1968. Since that time, understanding of transplant immunology and medical management has made heart transplantation in infants and children an important option for inoperable patients or those with end-stage cardiac disease. The indications for pediatric heart transplant were defined by the American Heart Association as:

• 1.

  Need for ongoing intravenous inotropic or mechanical circulatory support

• 2.

  Complex CHD not amenable to conventional surgical repair or palliation or for which the surgical procedure carries a higher risk of mortality than transplantation

• 3.

  Progressive deterioration of ventricular function or functional status despite optimal medical care

• 4.

  Malignant arrhythmia or survival of cardiac arrest unresponsive to medical therapy, catheter ablation, or an automatic implantable defibrillator

• 5.

  Progressive pulmonary hypertension that could preclude future transplantation

• 6.

  Growth failure secondary to severe CHF unresponsive to conventional medical therapy

• 7.

  Unacceptably poor quality of life

Children aged 11 to 17 years account for the greatest number of transplants in the pediatric population. Fig. 50.4 demonstrates the reasons for heart transplantation among different pediatric age groups. Examples in the neonate for which cardiac transplantation has been used as primary palliation include hypoplastic left heart syndrome with significant cardiac or extracardiac comorbidities, pulmonary atresia with intact ventricular septum and presence of coronary sinusoids, complex heterotaxy or unbalanced complete AV septal defects with poor common AV valve function, and single ventricle hearts where the dominant semilunar valve is severely insufficient. When considering transplantation there is a balance between the success of palliative surgery and the availability of organs for transplantation. For example, survival of patients undergoing surgical palliation of hypoplastic left heart syndrome (HLHS) has continued to improve. With the availability of infant donors increasing only slightly over this period of time ( Table 50.2 ), the balance for treatment of these newborns has shifted toward surgical palliation with the Norwood or hybrid Norwood procedures as the preferred treatment option over transplant. As a result, a decreasing frequency of neonatal transplants has been seen over the last 30 years.

Given the limited availability of organs, survival to transplant remains an obstacle in pediatric heart transplantation. Specifically in the neonate, the donor pool has remained limited as infant mortality has improved. The use of ABO-incompatible heart transplant protocols has emerged as an option for mitigating the limited neonatal donor pool. Evidence supporting use of these protocols has been demonstrated by comparable outcomes for ABO-incompatible and ABO-compatible heart transplantation in children. One philosophy is that the immature immune system of the neonate may slow the production of donor-specific antibodies. This may also explain an observed survival advantage in children who receive their transplant prior to 1 month of age versus those between 1 and 12 months. Other considerations may be an immunologic window where graft rejection and transplant coronary artery disease are limited.

Once transplanted, the long-term survival of infants who undergo heart transplantation in general is quite good. The 10-year survival in infants continues to improve, with reported rates as high as 74%.

Ventricular Assist Devices

Over the past several years, mechanical circulatory support devices have increasingly been developed for the pediatric population to serve as a bridge for postoperative cardiac recovery or heart transplantation. While the availability of devices for neonates lags far behind older children and adults, options are now available.

The mechanical circulatory support device approved for use in children is the Berlin Heart EXCOR pediatric ventricular assist device (VAD). This is a pneumatically driven device that comes in five sizes, with the smallest of the devices delivering a volume of 10 mL per stroke. One or two devices can be implanted to support one or both ventricles, respectively. Studies have looked at survival and complications in infants in the 3 to 5 kg range and a corrected gestational age of at least 37 weeks of age, in comparison with older children. Early mortality was increased in association with lower body weight. In the 33 infants included in the study who were less than 5 kg, 64% died following VAD implantation.

Given the challenges of the use of current VADs in infants, other devices continue to be developed and are either in the experimental stage or available for compassionate use. The development of these smaller devices has been supported, in part, by the Pediatric Circulatory Support Program of the National Heart, Lung, and Blood Institute. Several devices are in various stage of testing, some of which are small enough in size for use in infants.

Patent Ductus Arteriosus and Aortopulmonary Window

Most children are born with a patent ductus arteriosus (PDA) that typically closes within the first week of life. Prematurity is a risk factor for a persistent PDA. Persistent PDA in term infants occurs more commonly in females and may have a genetic component in some patients, as suggested by an animal model of inbred poodles and linkage to chromosome 12.

The pathophysiology of a PDA largely depends on the degree of shunting from the aorta to the pulmonary artery, which is determined by the inner diameter and length of the PDA and the relative pulmonary and systemic vascular resistances. If the PDA diameter is small, the ductus itself will provide the primary site of resistance to flow, and the shunt will be small. In the case of a larger PDA, low PVR may allow for a significant shunt that places the patient at risk for developing heart failure and, eventually, pulmonary vascular disease. The low resistance pathway through the lungs provides a route for diastolic run-off from the aorta that can lead to decreased coronary perfusion pressure, resulting in myocardial ischemia and systemic steal, resulting in end-organ dysfunction.

Clinically, patients with a small shunt will be asymptomatic. With a larger PDA shunt, the progressive decline in PVR postnatally will cause an increase in left-to-right shunt flow with signs of increasing heart failure. The murmur in a child with a PDA is generally continuous and has been described as a “machinery” murmur in the left infraclavicular region. The character of the murmur, however, varies greatly, although the continuous nature is generally present once the PVR has declined. Examination of the patient with a PDA will also include a wide pulse pressure because of decreased diastolic pressure and bounding pulses.

The diagnosis of PDA, when suspected on examination, can nearly always be confirmed by echocardiography. Even in the face of high PVR with limited left-to-right shunting, differences in the pulse waveforms between the aorta and pulmonary artery will allow left-to-right and/or right-to-left shunting to be observed by color Doppler imaging. As the degree of left-to-right shunting increases the left heart becomes volume overloaded, which also can be assessed by echocardiogram. In addition, retrograde flow will be seen in the proximal descending aorta when a large shunt is present. Cardiac catheterization is rarely needed unless device closure of the PDA is considered.

The prognosis for small PDAs is quite good, and debate exists as to whether closure of “silent” PDAs, incidentally identified by echocardiography, should be performed. With the most recent recommendations from the American Heart Association suggesting that PDAs do not require subacute bacterial endocarditis prophylaxis, there is little need to close these small vessels.

Because of the long-term concerns of pulmonary overcirculation and the development of pulmonary vascular disease, closure of hemodynamically significant PDAs is recommended particularly in the preterm infant. In the preterm infant closure is usually attempted medically with the use of prostaglandin inhibitors such as indomethacin and ibuprofen. Surgical ligation and division can readily be performed through a lateral thoracotomy. However, coil or device closure in the catheterization lab has a lower morbidity and success rates equal to surgery. As a result, catheter closure of PDAs has become the preferred method in nonpremature infants. Success of device closure depends in part on the weight of the infant and size and shape of the PDA. With the current array of devices available, closure can be safely performed in most infants weighing more than 4 kg and can be considered in some infants weighing between 2.5 and 4 kg. Percutaneous closure of the PDA in the extremely low birth weight population (<2 kg) is being increasingly explored with good efficacy and low adverse event rates.

Aortopulmonary (AP) window occurs when there is direct communication between the aorta and main pulmonary artery and is a rare lesion with an incidence of 0.2%. Nearly half of patients with an AP window will have an associated cardiac anomaly. These lesions nearly always result in a large degree of left-to-right shunting. Patients will show signs of CHF on examination and have physical and laboratory findings similar to those for a large PDA. Generally, all AP windows should be closed surgically when they are identified.

Ventricular Septal Defect

VSDs are the most common type of CHD (excluding bicuspid aortic valve). Generally, VSDs are classified into four types ( Fig. 50.5 ):

• 1.

  Membranous/Perimembranous

• 2.

  Muscular (e.g., apical muscular defects)

• 3.

  Inlet (e.g., atrioventricular septal defects)

• 4.

  Outlet (e.g., subpulmonary defects)

The perimembranous VSD is the most common of the four types and has variably been referred to as membranous, paramembranous, or infracristal. From the right ventricular side of the heart, these defects lie under the septal leaflet of the tricuspid valve below the crista supraventricularis and posterior to the papillary muscle of the conus. Muscular VSDs can occur in isolation or as multiples (“Swiss cheese septum”) and, as the name implies, can occur anywhere in the muscular septum. Apical muscular VSDs are the most common and are sometimes difficult to accurately size by echocardiography because of the heavy trabeculations at the apex of the right ventricle. Inlet VSDs are located posterior and inferior to perimembranous defects, and although the nomenclature is controversial, this is the location of the defect in patients with complete atrioventricular septal defects. The location of the VSD in patients with outlet defects is above the crista supraventricularis and typically undermines the right aortic valve leaflet. A variety of synonyms have been used for outlet VSDs including subarterial, subaortic, supracristal, and conal VSD.

The clinical importance of any VSD is dependent upon the size of the defect and the relative pulmonary-to-systemic vascular resistance, which together determine the degree of left-to-right shunting. An additional consideration with outlet VSDs is the degree to which the right coronary cusp of the aortic valve prolapses into the defect and results in aortic insufficiency. Defects whose cross-sectional area is equal to, or greater than, the cross-sectional area of the aortic valve will not restrict flow leaving the left ventricle and entering the right ventricle. In this case, the degree of shunting will be determined by the relative resistance to flow in the pulmonary and systemic vascular beds. The normal postnatal decline in PVR will result in a progressive increase in left-to-right shunting and signs of CHF. A small percentage of children do not have the usual postnatal decline in PVR and may never develop signs of pulmonary overcirculation and heart failure despite the presence of a large VSD. This is an indication for early surgical closure of the defect.

When the VSD is small relative to the aortic valve, the defect itself will be the primary point of resistance to shunt flow. In this case, changes in PVR will have little impact on the degree of left-to-right shunting.

An important associated lesion that is critical to rule out is coarctation of the aorta. The coarctation results in a fixed elevated systemic vascular resistance that can result in significant left-to-right shunting even in the presence of a small VSD. In this case, medical therapy is often unable to control CHF symptoms, and surgery is needed.

The volume of shunted blood is most accurately quantitated at cardiac catheterization based on the step-up in oxygen saturation from the right atrium (mixed venous) to the pulmonary artery and is represented as the ratio of pulmonary-to-systemic blood flow (Qp:Qs). Generally, a Qp:Qs less than 1.5 is considered below the threshold for surgery, while a Qp:Qs greater than 2.0 is an indication for surgery. The Qp:Qs can also be estimated by echocardiography and by magnetic resonance imaging (MRI). Modern era management of isolated ventricular septal defects is rarely determined by Qp:Qs quantification and relies more heavily on clinical evaluation.

The examination of the patient with a VSD depends on the magnitude of the shunt. Small defects that provide considerable restriction to flow often have the loudest murmur. The rapid drop in PVR immediately after birth often allows VSD murmurs to be heard in the newborn nursery, although the full extent of the murmur, and perhaps a thrill at the lower left sternal border, may not be appreciated for several weeks. The murmur may have a more ejection quality in the newborn nursery in the face of high PVR and somewhat elevated right ventricular pressure. The more typical holosystolic murmur will be more apparent as the PVR falls.

With large VSDs, little or no murmur may be heard depending on the PVR. With low PVR, signs of heart failure will likely be present including tachypnea with nasal flaring and retractions, tachycardia, diaphoresis, poor feeding, and diminished weight gain. A systolic murmur at the lower left sternal border (caused by flow across the VSD) or upper left sternal border (caused by increased flow across the right ventricular outflow tract [RVOT]) may be heard along with a diastolic inflow rumble (an absence of silence) at the apex. If PVR is high, the pulmonic component of the second heart sound may be increased although difficult to appreciate. Occasionally, large defects may allow transient right-to-left shunting to occur, particularly when the infant is crying.

In patients with an outlet VSD, the holosystolic murmur is often present, but the murmur is located higher on the left sternal border. Care should be taken to listen for the diastolic decrescendo of aortic insufficiency at the mid-left sternal border or at the apex.

The evaluation of the infant with a suspected VSD should include an ECG, chest x-ray, and echocardiogram. In infants, the ECG may not be distinctive unless an inlet VSD is present. Obtaining a chest x-ray, even in the neonate, is important in order to assess heart size and pulmonary vascular markings. It can also be an important tool in the follow-up of newborns with VSDs when used to assess progression in left-to-right shunting as the PVR declines. Echocardiography is the gold standard for characterizing the location and size of VSDs. Associated lesions, such as coarctation of the aorta, can also be readily assessed by echocardiography. Doppler studies can estimate the degree of restriction by calculating the pressure drop at the defect. M-mode measurements can be used to determine left ventricular dimensions, which will be increased when a significant left-to-right shunt is present. As mentioned above, cardiac catheterization can accurately quantitate the degree of shunting but is rarely needed in the initial assessment of the newborn with VSD.

Up to 80% of small, muscular VSDs and 30% to 50% of perimembranous defects will close spontaneously. It is uncommon for these defects to increase in size, although the degree of left-to-right shunting can increase as PVR drops. Occasionally, inlet VSDs will undergo closure secondary to chordal attachments of the AV valves, but closure is generally present at birth if it is going to occur. Outlet VSDs virtually never close and have the associated risk of progressive aortic insufficiency because of prolapse of the right coronary cusp into the defect.

The short-term consideration in following patients with VSDs is the management of CHF if the left-to-right shunt is excessive. Medications that are used include diuretics to augment fluid shifts and less frequently afterload reduction with agents such as angiotensin-converting enzyme inhibitors. The primary goal in controlling CHF is to allow the newborn to grow adequately and hopefully allow progressive closure of the VSDs. Weight gain is a useful and objective measure to follow.

The long-term goal of therapy or intervention is to prevent the development of irreversible pulmonary vascular occlusive disease. Shunts with a Qp:Qs greater than 2.0 are at long-term risk of developing Eisenmenger disease, and closure of the defect is warranted beyond 2 to 4 years of age when further decline in defect size is unlikely.

If medical therapy fails to control heart failure and the infant exhibits failure to thrive, surgical closure of the defect in the first 6 months of life is usually necessary. Surgical closure is also indicated in the 6- to 12-month-old child with a large VSD who has not demonstrated signs and symptoms of CHF due to lack of decline in PVR. In these infants, irreversible changes in the pulmonary vasculature may occur if the pressure load is not removed from the lungs. As mentioned previously, defects with a Qp:Qs greater than 2.0 and outlet defects also require closure. The use of pulmonary artery banding is falling out of favor for palliation of patients with VSDs unless the patient’s clinical condition precludes complete repair. There is growing use of hybrid procedures where the surgeon and interventional cardiologist work together to close defects in small children. This combined approach has successfully been applied to the closure of muscular VSDs in infants that are positioned in a location that is difficult for the surgeon to visualize from a right atrial approach.