The ability to diagnose prenatal cardiovascular disease has improved dramatically due to education and improved ultrasound technology. As our ability to image increases, so does the potential for generation of new knowledge concerning the fetal cardiovascular state. Sophisticated imaging techniques allow us to assess previously puzzling physiologies at earlier and earlier points in gestation. It is crucial that the natural history of congenital cardiac disease be mapped out accurately before we can appropriately undertake a strategy of perinatal cardiac intervention for specific lesions.48
The color Doppler sonographic findings in specific heart defects49 are summarized in Table 6-2.
Table 6-2COLOR DOPPLER FINDINGS IN COMMON CARDIAC ANOMALIES ||Download (.pdf) Table 6-2 COLOR DOPPLER FINDINGS IN COMMON CARDIAC ANOMALIES
|Cardiac Defect ||Four-Chamber View ||LV Outflow Tract View ||Three-Vessel View |
|Tricuspid atresia with ventricular septal defect |
|Absent connection between RA and RV; hypoplastic RV, VSD present || |
Absent flow from RA to RV
Blood from RA flows across foramen ovale to LA, and then in diastole to LV; unilateral perfusion across LV inflow tract; left to right shunt across the VSD into small RV
|Noncontributory or depending on the ventriculo-arterial connections ||Pulmonary stenosis often evident with antegrade flow |
|Tricuspid dysplasia and Ebstein's anomaly |
TV dysplasia: thickened valve leaflets
Ebstein's anomaly: apical displacement of TV leaflets within the RV
RA dilatation common; gross cardiomegaly in severe cases
Spectral Doppler can be used to measure pressure gradient and duration of regurgitation
|Noncontributory ||Tiny pulmonary artery when associated obstruction of RV outflow tract: antegrade flow in pulmonary stenosis; retrograde flow in severe forms |
|Pulmonary atresia with intact ventricular septum |
|RV hypoplastic, normal-sized or, rarely, dilated; poor contractility of RV; reduced TV movement; atretic pulmonary valve ||Reduced or absent tricuspid flow; TR may be evident during systole; rule out ventriculo-coronary fistula ||Noncontributory ||Lack of antegrade flow across pulmonary valve; retrograde flow through DA; pulmonary trunk smaller caliber than ascending aorta |
|Pulmonary stenosis |
|Narrowing of semilunar valves; poststenotic dilatation of pulmonary trunk; hypokinetic and hypertrophied RV in severe cases ||Tricuspid insufficiency in severe cases or often in third trimester ||Noncontributory ||Antegrade turbulent flow in pulmonary trunk; rarely retrograde flow through DA in severe cases |
|Aortic stenosis |
|Narrowing of semilunar valves; poststenotic dilatation of the ascending aorta ||Noncontributory ||Antegrade turbulent flow with aliasing is characteristic; pulsed Doppler shows high velocities (>2 m/s) ||Turbulent flow in dilated proximal aortic arch |
|Hypoplastic left heart syndrome/critical aortic stenosis with left ventricular dysfunction |
|Aortic valve atretic or severely stenotic; LV small, normal-sized or dilated, but noncontractile; mitral valve atretic or stenotic ||Unilateral perfusion of RV; reduced or absent diastolic filling of LV; abnormal left to right shunt across interatrial septum ||Hypoplastic aorta, often with retrograde flow In critical stenosis, antegrade turbulent flow may be observed ||Retrograde perfusion in hypoplastic aortic arch |
|Coarctation of the aorta |
|Narrowing of distal aortic arch or of the whole arch in tubular hypoplasia; LV may be smaller than RV; VSD may be present in some cases with tubular hypoplasia ||LV may be smaller than RV ||Antegrade flow across the aortic valve; aorta may be of small caliber ||Aortic arch smaller than ductal arch; aortic arch flow usually antegrade, unless severe |
|Ventricular septal defect |
|Defect usually involves perimembranous septum, occasionally inlet or muscular septum; defects larger than 3 mm can be identified with two-dimensional ultrasound ||Color Doppler identifies small muscular VSDs and confirms larger VSD ||Color flow across perimembranous defect ||Noncontributory |
|Atrioventricular septal defect |
|Septal valve leaflets deformed or absent, with common AV junction and deficient crux ||"H"-shaped biventricular diastolic flow across left and right inflow tracts with communication at level of AV valves; TR and MR during systole ||Noncontributory ||Noncontributory |
|Tetralogy of Fallot |
|VSD; overriding aorta; infundibular pulmonary stenosis; RV hypertrophy (not evident prenatally) ||Non-contributory in most cases ||"Y"-shaped systolic flow from both ventricles into overriding aorta ||Antegrade (turbulent) flow in tiny pulmonary trunk In severe cases retrograde flow through DA |
|Double-outlet right ventricle |
|Aorta and pulmonary trunk arise from RV; LV may be smaller than RV; VSD ||VSD with left-to-right shunt may be present; small LV may be evident ||Color flow within aorta and pulmonary trunk arising from RV, usually with a parallel course ||Obstruction of the outflow tracts may be seen |
|Complete transposition of the great arteries |
|Aorta arises from RV and pulmonary trunk from LV ||Non-contributory ||Parallel course of great vessels; subpulmonary VSD may be detected ||Usually one great vessel seen (aorta) |
|Truncus arteriosus |
|Single great artery, often overriding the interventricular septum, bifurcating into aorta and pulmonary trunk in Type I ||Non-contributory ||Common arterial trunk seen as a single large vessel overriding interventricular septum; truncus insufficiency may be present ||DA often absent; tiny pulmonary artery |
Hypoplastic Left Heart Syndrome
Hypoplastic left heart syndrome makes up to 4.8% to 9% of congenital heart disease. The incidence is between 0.1 and 2.7 per 1000 live births. It is considered to be the most common cause of cardiac death during the first week of life.45,50
The fetal left ventricle is predominantly filled with oxygenated blood that returns from the placenta and traverses the foramen ovale.51 If blood flow across the foramen ovale is diminished or reversed, the combined cardiac output is redistributed to the right ventricle and pulmonary artery, resulting in enlargement of the right heart structures and creating less impetus for normal growth of left heart structures, possibly evolving into hypoplastic left heart syndrome. Perhaps the most well-recognized mechanism for decreased flow or reversal of flow through the foramen ovale in utero is the presence of severe aortic valve disease.45,52,53 With significant aortic valve stenosis, alterations in left ventricular compliance may occur, either secondary to the development of left ventricular hypertrophy or secondary to the development of left ventricular dilation and dysfunction. Endocardial fibroelastosis, a poorly understood phenomenon where the endocardial lining of the left ventricle becomes fibrotic, may also be present. As the disease state progresses, with subsequent elevation in left atrial pressure, flow across the foramen ovale becomes bidirectional and eventually left to right, the result of which may be the cessation of left ventricular growth.54
Although a multifactorial mode of inheritance is likely, the recurrence risk among siblings suggests transmission via an autosomal recessive mode. In addition, pedigree analyses have demonstrated a 12% prevalence of cardiac abnormalities involving the left ventricular outflow tract in first-degree relatives of patients with hypoplastic left heart syndrome.55
Hypoplastic left heart syndrome is associated with chromosomal anomalies in about 2% of cases, particularly Turner syndrome (XO), trisomies 13 and 18, and rarely microdeletion of chromosome 22q11.31
Recent advances in two-dimensional and Doppler echocardiography have made it feasible to diagnose all forms of congenital heart disease in the fetus. Hypoplastic left heart syndrome is one of the most common structural lesions diagnosed prenatally, as a screening obstetric ultrasound will preferentially identify lesions that dramatically alter the 4-chamber view (Figure 6-17).49,56,57 The prenatal diagnosis of hypoplastic left heart syndrome is made when a small, muscle-bound left ventricular chamber is identified.
Four-chamber view of a 24-week gestational age fetus with hypoplastic left heart syndrome. The left ventricle (LV) chamber size is smaller compared with the right ventricle (RV). The lining of the LV is echo-bright, indicative of endocardial fibroelastosis. RA, right atrium; LA, left atrium.
Clues to fetal sonographic diagnosis are a small echogenic left ventricle or absent left ventricle (Figure 6-18), a small left atrium, and left-right atrial shunt (Figure 6-19). There is a hypoplastic ascending aorta and enlarged pulmonary artery with retrograde flow in the aortic arch (Figure 6-20). Left ventricle to coronary fistulous connections may be present.
Outflow tract view of a 28-week gestational age fetus with hypoplastic left heart syndrome. Note the enlargement of the right ventricle (RV) and the pulmonary artery (PA). There is no evidence of a left ventricular chamber.
Doppler of the flow through the patent foramen ovale (PFO) in a 29-week gestational age fetus with hypoplastic left heart syndrome. Note the flow from the left atrium (LA) to the right atrium (RA), the opposite of the normal pattern.
Pulsed Doppler demonstrating reversed flow in the distal aortic arch in a 33-week gestational age fetus with hypoplastic left heart syndrome (left panel). Note the red flow in the color Doppler image of the arch (right panel).
Most commonly, aortic atresia is associated with an underdeveloped left ventricle, but it can start with a normal-sized left ventricle, progressing to a severely hypoplastic ventricle with gestation. The degree of endocardial fibroelastosis can progress depending on left ventricle outflow tract obstruction.
Serial echocardiographic follow-up is indicated in these fetuses, paying particular attention to growth of left heart structures and patterns of blood flow across the foramen ovale and transverse aortic arch. Importantly, it now seems feasible to reliably select fetuses for prenatal intervention, using both anatomic and physiologic markers.46
The challenge for the fetal echocardiographer today is to recognize the potential for the evolution of hypoplastic left heart syndrome and to diagnose the severely restrictive or intact atrial septum in this patient group prior to birth, as these patients may benefit from prenatal intervention.
What to Expect after Delivery
If the fetus remains well compensated and the lesion is isolated, delivery can be at term in a tertiary care center. Following delivery, prostaglandins are initiated to maintain ductal patency, and an echocardiogram is performed to confirm the diagnosis. If severe atrial septal restriction is suspected on the prenatal ultrasound, interventional cardiology, and/or cardiothoracic surgery should be immediately available.
Early studies that focused on the impact of prenatal diagnosis of hypoplastic left heart syndrome appeared to suggest that prenatal diagnosis had a negative influence on short-term survival. This may be related to a weighting toward prenatal diagnosis in a sicker subpopulation of fetuses. More recently it has been demonstrated that fetal echocardiography has a positive impact on survival. Infants with a prenatal diagnosis of hypoplastic left heart syndrome were found to have less preoperative acidosis than those diagnosed after birth as well as an improved preoperative status and postoperative survival.45,56,57 Today, stage I Norwood operation in a term newborn has a greater than 85% survival rate.
Prenatal diagnosis may improve the outcome of the fetuses with hypoplastic left heart syndrome at highest risk by identifying those who will need urgent balloon atrial septostomy. It will also help to separate others that are able to continue their prenatal course with less severe disease. The influences of these factors on outcome of hypoplastic left heart syndrome have not been evaluated. In rare cases of critical aortic stenosis with intact septum there may be mitral regurgitation (Figure 6-21) and enlarged left atrium and left ventricle (Figure 6-22).
Mitral regurgitation in a 29-week gestational age fetus with critical aortic stenosis and marked enlargement of the left atrium and left ventricle.
Enlarged left atrium and left ventricle in the fetus shown in Figure 6-21, illustrating intact atrial septum (IAS). RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle; MV, mitral valve.
Coarctation of the aorta occurs in approximately 8% to 10% of patients with congenital heart disease, with a male preponderance (2:1). Aortic arch anomalies accounted for 6.1% of all cardiovascular lesions detected antenatally in the combined series of Allan and colleagues. In this series, out of a total of 138 fetuses with arch anomalies, there were 46 survivors of 79 continuing pregnancies (59%).58
The aortic arch and its branches develop during the sixth to eighth week of human gestation. The embryologic third aortic arches persist as the common carotid arteries. The left fourth aortic arch forms the thoracic aortic arch and isthmus, and the right fourth arch normally involutes. The embryologic sixth aortic arches persist as the proximal pulmonary arteries, with the left sixth aortic arch developing distally into the ductus arteriosus. A thoracic coarctation, therefore, is a manifestation of an abnormality in development of the embryologic left fourth and sixth aortic arches.59 The underlying cause of the abnormal arch development is not well understood.
The pathophysiology of coarctation varies with the severity of the stenosis and is also affected by the presence of associated lesions, such as patent ductus arteriosus, ventricular septal defect, and aortic or mitral stenosis. The clinical presentation of coarctation also varies widely, ranging from heart failure in the newborn to asymptomatic hypertension or a murmur in an older child.
The genetic component to coarctation has long been recognized in the Turner XO syndrome, in which about 35% of patients are affected. Recent data suggest that there is a more important genetic influence on the development of left-sided obstructive lesions, including coarctation, than previously recognized.60
Left-sided obstructive lesions account for approximately 14% of congenital heart diseases. There is a relatively consistent excess in males compared to females (3:1.5). The observed sibling recurrence risk for these defects is approximately 2% and the risk if the mother is affected is about 4%.30
Prenatal diagnosis of coarctation of the aorta can be difficult. However, the diagnosis can be inferred from dilatation of the right atrium, right ventricle, and pulmonary artery when these structures are compared with those of the left heart (Figure 6-23A). On direct echocardiographic examination of the aortic arch, arch hypoplasia or interruption of the aortic arch can be recognizable prenatally. Typically, the arch in coarctation is hypoplastic and elongated between the left carotid and left subclavian arteries. Doppler shows increased velocity in the aortic isthmus in some cases (Figure 6-23B).
A: Four-chamber view of a 33-week gestation fetus, confirmed to have coarctation of the aorta postnatally. There is mild disproportion at the atrial (right atrium [RA] greater than the left atrium [LA]) and ventricular levels (right ventricle [RV] greater than left ventricle [LV]). B: Doppler display across the aortic isthmus (AO ISTH) in a 31-week gestational age fetus with coarctation of the aorta. The peak velocity is 1.44 m/s and there is increased diastolic velocity.
Follow-up includes serial antenatal fetal echocardiography studies at 4-week intervals. If the fetus remains well compensated and the lesion is isolated, delivery can be at term vaginally in a tertiary care center.
What to Expect after Delivery
Once the baby is delivered, an echocardiogram should be performed to determine arch size and ductal dependency. Following delivery, prostaglandin E1 (PGE1) may be initiated if the coarctation is severe. Otherwise, some cases of prenatally diagnosed coarctation of the aorta may not be ductus dependent and may not require surgical correction in the neonatal period.
A retrospective review of infants with normal karyotype with coarctation of the aorta diagnosed between 1994 and 1998 showed a higher likelihood of cardiovascular collapse or death in those infants diagnosed after birth. In this group, 30% died before surgery could be performed. Conversely, both pre- and postoperative mortality was 0% in the infants diagnosed by fetal echocardiography.44
Isolated pulmonary stenosis represented 0.8% of cases of structural cardiac malformation diagnosed in fetal life. Pulmonary stenosis, with and without other associated lesions, occurs in 25% to 30% of all patients with congenital heart disease.
The exact embryologic process resulting in pulmonary valve stenosis is not well understood. Maldevelopment of the distal part of the bulbus cordis has been proposed.
When the degree of valvular pulmonary stenosis is severe enough to cause a decrease in fetal right ventricular output, a larger-than-normal atrial right-to-left shunt is established in utero. This condition has been termed critical pulmonary stenosis. The right ventricle is often hypoplastic because of severe hypertrophy and the effects of reduced flow through the right ventricle during development.
Pulmonary stenosis can occur as part of Noonan, Alagille, or Williams syndrome. It is very rare for isolated pulmonary stenosis to be associated with chromosomal anomalies. Familial occurrence of pulmonary stenosis has been reported. In the Second Natural History Study of Congenital Heart Defects, the occurrence of definite and possible congenital cardiac defects in 1356 siblings of 449 patients with valvar pulmonary stenosis was 1.1% and 2.1%, respectively.61
The echocardiographic findings depend on the degree of pulmonary obstruction. The right ventricle may show hypertrophy (usually), dilatation (occasionally), or hypoplasia (depending on the degree of pulmonary obstruction). Right ventricle function may be decreased and this might decrease the Doppler velocities across the stenotic valve. The pulmonary artery is usually smaller than the aorta with thickened and restrictive leaflets. There is turbulence at the pulmonary valve with color Doppler and increased blood velocity (Figure 6-24). Frequently, there is systolic reversal of the pulmonary blood velocity with valvar or infundibular pulmonary stenosis. Pulmonary stenosis gradient in utero may not reflect the severity of the stenosis depending on the size of the patent ductus and right ventricle function.
A: Color Doppler of the right ventricular (RV) outflow tract shows color change at the pulmonary valve and into the main pulmonary artery (MPA), suggesting congenital valvar pulmonary stenosis. B: Continuous wave Doppler of severe pulmonary stenosis, compared with Figure 6-21A, in a fetus at 30 weeks' gestation. Note the high peak velocity in systole in the right ventricular outflow tract. This finding would predict an elevation of right ventricle pressure much greater than the left ventricle pressure.
The tricuspid valve will show restricted opening because of the decreased inflow. In critical pulmonary stenosis, there will be reverse flow across the ductus arteriosus.
The pregnancy course depends on the severity of the lesion and the gestational age at which the diagnosis is made. The intrauterine prognosis of critical pulmonary valve stenosis depends on the size of the foramen ovale and left ventricle function to support the combined cardiac output.
Pulmonary regurgitation in a structurally normal valve could be a sign of increased right ventricular afterload and heart failure. Failure of growth of the right ventricle and the pulmonary trunk may occur as the pregnancy advances. This is important in counseling, especially with regard to the possibility of biventricular surgical repair at birth.
What to Expect after Delivery
Central cyanosis may be present at birth, but while the arterial ductus is open may not be obvious. As the ductus constricts, pulmonary blood flow decreases and cyanosis becomes more apparent, typically within 48 hours, and may be severe enough to be life threatening. Although the right ventricular cavity is often relatively hypoplastic, the atrial communication is usually large enough to maintain cardiac output and prevent right heart failure at the expense of cyanosis. Symptoms of right-sided heart failure may be seen in some newborns with significant tricuspid insufficiency or may develop in untreated infants if the atrial communication becomes inadequate with growth.
The prognosis is dependent on the degree of pulmonary obstruction. Most patients with mild or moderate stenosis remain stable, and pressure gradients recorded early in life often decrease with growth. This is particularly true in patients with associated syndromes, such as Williams, Noonan, or congenital rubella; however, multiple peripheral pulmonary stenosis of severe degree may be progressive, and the prognosis is poor unless angioplasty, stent placement, or surgery is successful. Long-term prognosis after treatment is reasonably good, except for the high rate of reinterventions for residual pulmonary stenosis and pulmonary valve insufficiency. Complications include right ventricular failure, pulmonary artery thrombosis, and poststenotic aneurysmal dilation with pulmonary artery hemorrhage.
Pulmonary Atresia With Intact Ventricular Septum
Pulmonary valve stenosis or atresia with intact ventricular septum represents a spectrum of severity.
Pulmonary atresia with intact ventricular septum accounts for 2.5% to 4% of congenital heart disease and occurs in 1 in 2200 live births.
Kutsche and Van Mierop suggested that pulmonary atresia and ventricular septal defect occur early in cardiac morphogenesis, at or shortly after partitioning of the truncoconal part of the heart but before closure of the ventricular septum. Conversely, they suggest that pulmonary atresia and intact ventricular septum probably occur after cardiac septation.62
An interatrial communication (either atrial septal defect or patent foramen ovale) and patent ductus arteriosus are necessary for survival. The high pressure in the right ventricle is often decompressed through dilated coronary fistulous connections into the left or right coronary artery. The obstruction of the proximal coronary arteries, which is often present, can cause high surgical mortality. Right atrium dilatation and hypertrophy may be one of the earliest clues to right ventricle outflow tract obstruction. With redistribution of flow to the left atrium and left ventricle, the left heart chambers dilate to accommodate the preload that is critical to sustain the equivalent of a combined ventricular output. Tricuspid regurgitation is commonly present. The tricuspid valve orifice is usually hypoplastic and the tricuspid valve opening appears restricted.
When there is a previous baby with the same condition, this congenital heart disease may be an autosomal recessive trait. In the absence of positive family history and normal karyotype, including fluorescence in situ hybridization (FISH) for 22q11.2, we may assume a multifactorial inheritance, and hence the estimated recurrence risk is around 2%.30
The condition is usually associated with an abnormal 4-chamber view, hypoplastic right ventricle, poorly contracting thick-walled ventricle, small tricuspid valve annulus (compare to mitral valve annulus and get a Z score value of the annulus), tricuspid regurgitation (usually at high Doppler velocity), variable size of main pulmonary artery and branches, absence of forward flow across pulmonary valve or main pulmonary artery, no antegrade flow across the pulmonary valve (in systole), reverse flow in the ductus arteriosus (aorta-pulmonary), and fistulous connections from the right ventricle to the coronary arteries, which may result in bidirectional, high velocity flow in the coronary arteries.
Not infrequently, the ductus venosus Doppler signal is abnormal, with increased pulsatility index and reversal of flow during atrial contraction. Being able to visualize coronary flow prenatally points toward associated ventriculo-coronary fistulous connections.63 However, it is difficult to predict echocardiographically those who may have a right-ventricle-dependent circulation.
The intrauterine prognosis depends on both the size of the foramen ovale and the left ventricle function to support the combined cardiac output. Follow-up includes serial antenatal studies at 4-week intervals, looking for right ventricle size and function, endocardial fibroelastosis, congestive heart failure, left ventricle function, and growth of pulmonary arteries and branches.
Fetal pulmonary valvuloplasty has been performed in an attempt to preserve right ventricle growth in the hope this will maximize the chances of a biventricular repair. However, at this point, the numbers are small, and there are no long-term follow up data and no clear-cut selection criteria as to which cases may benefit from prenatal intervention. Progressive signs of heart failure on cardiovascular profile score of seven or less may indicate a poor prognosis.
The mode of delivery is decided according to the functional condition of the left ventricle. Usually vaginal delivery is possible and should be at term or near term in a tertiary care center. Conditions for cesarean delivery are left ventricle dysfunction, such as fractional shortening of less than 25%, evidence of progressive flow restriction through the foramen ovale, and fluid accumulation in either the pleural or peritoneal cavities.
What to Expect after Delivery
After delivery, PGE1 should be administrated to keep the ductus open, increasing pulmonary blood flow and raising the arterial oxygen saturation. Therapeutic balloon valvuloplasty of the pulmonary valve is being performed in some centers. Therapeutic balloon atrial septostomy must be performed in the rare situation of tiny right ventricle and restrictive patent foramen ovale.
Pulmonary atresia with intact ventricular septum lies at the severe end of the spectrum of congenital heart disease. Factors that affect the outcome include size of the right ventricle, ventriculo-coronary fistulous connections, coronary artery stenosis, and chromosomal abnormalities (relatively uncommon).
Management strategies for pulmonary atresia with intact ventricular septum continue to evolve and must include assessment of the coronary circulation. The presence of ventriculo-coronary fistulous connections may promote coronary artery stenosis and interruption, and aortic diastolic pressure may not be sufficient to drive coronary blood flow when obstructive lesions are present within the coronary circulation. Clinically, significant coronary artery stenosis is not detectable before birth with current technology. However, this finding can certainly impact the management options and long-term outcome of an affected infant.
The presence of right-ventricle-dependent coronary arteries is a contraindication to a biventricular repair. In a coronary circulation that is wholly or partially right ventricular dependent, it is the blood that gets into the right ventricle at systemic or above-systemic right ventricular systolic pressure that supplies the myocardium in a retrograde fashion. Interference with blood flow into the right ventricle or reduction of right ventricular systolic pressure in situations in which the coronary circulation is right ventricular dependent may result in myocardial ischemia, infarction, and sudden death.
Ebstein's Anomaly of the Tricuspid Valve or Tricuspid Dysplasia
Ebstein anomaly occurs in about 1 to 5 per 200,000 births and represents less than 1% of all congenital heart disease.64 Lithium exposure at the time of conception has been implicated as a cause for this defect.65
Characteristic pathologic findings include displacement of the septal and posterior leaflets of the tricuspid valve into the right ventricle, so that a proportion of the right ventricle is incorporated into the right atrium (atrialized right ventricle), resulting in functional hypoplasia of the right ventricle and tricuspid regurgitation. The septal leaflet is typically rudimentary in more severe forms, but may be thickened only at its edges with minimal displacement from the true annulus in milder forms. The posterior leaflet may be thickened with abnormal chordal attachments tethering it to the ventricular myocardium in more severe forms of the lesion. The anterior leaflet is often large and quite redundant, resembling a sail. Abnormal chordal attachments to this and the posterior leaflet are often the cause of severe insufficiency. Although the atrialized portion of the right ventricular anterior wall may be thin, the distal unaffected portion of the right ventricular wall is usually normal in thickness.
Most cases of Ebstein anomaly occur sporadically, although familial cases have been reported. Associated lesions are not uncommon. In most cases, an interatrial communication is present either in the form of a patent foramen ovale or a true atrial septal defect. Ventricular septal defects and pulmonary stenosis or atresia are also occasionally found. The incidence of this lesion is higher than expected in infants born to women who have ingested lithium early during the pregnancy.66
Fetal echocardiography has provided the ability to determine the presence of Ebstein anomaly, because the distinctive tricuspid valve displacement can be detected as well as the marked right heart enlargement (Figure 6-25). Two-dimensional echocardiogram also gives the degree of displacement of the valve into the right ventricular cavity and prognostic features can be assessed. The presence of associated lesions also can be well demonstrated. With the addition of Doppler and color flow techniques, the degree of tricuspid insufficiency or stenosis can be assessed accurately along with intracardiac shunting patterns.
Marked enlargement of the right atrium (RA) and right ventricle (RV) is present in this 24-week gestational age fetus with severe tricuspid regurgitation and Ebstein malformation.
Tricuspid valve abnormalities in the fetus range from mild displacement of the septal leaflet with mild insufficiency to severe displacement, absent valve coaptation with severe insufficiency, atrialization of the right ventricle, and functional pulmonary atresia.67 Because of the truly massive proportions assumed by the right ventricle, severe forms of tricuspid insufficiency that present early may restrict growth of functional lung tissue, further decreasing the likelihood of postnatal survival. Even with anticipatory care and more novel approaches to postnatal management, it was recently shown that 27% died in utero and only 21% survived beyond the neonatal period. Factors indicating severity include the absence of anterograde flow across the pulmonary valve due to severe tricuspid regurgitation, ratio of the combined area of the right atrium and atrialized right ventricle to that of the functional right ventricle and left heart in 4-chamber view at end-diastole greater than 1.5, and in extreme cases fetal hydrops. If they appear, an elective delivery should be performed.64
What to Expect after Delivery
An additional problem exists in the neonatal period, that of increased pulmonary vascular resistance. In more severe cases of Ebstein anomaly, the ability of the right ventricle to propel blood in an antegrade direction is compromised. Therefore, the right ventricle may not be able to generate adequate pressure to open an otherwise normal pulmonary valve. This results in functional pulmonary atresia. In this case, the neonate may be extremely cyanotic and dependent on patency of the ductus arteriosus for pulmonary blood flow. As pulmonary vascular resistance diminishes, the right ventricle may be able to pump blood in an anterograde direction across the right ventricular outflow tract. The degree of tricuspid insufficiency and right-to-left atrial level shunt then diminishes, and the infant becomes less cyanotic.
The prognosis for the fetus diagnosed in utero with significant tricuspid valve disease is extremely poor.64 Survival rates described are 49% at birth in fetuses with Ebstein anomaly or tricuspid valve dysplasia, but approximately 20% beyond 1 month of age.64
Although there are reports of patients with Ebstein anomaly living many decades, most authors describe a mean age of death at about 20 years, with about one-third dying before the age of 10 years.68 Surgical repair of Ebstein anomaly, especially in infants, remains a major challenge. Patients with milder forms of the disease can live well into adulthood, and women can become pregnant and deliver normal-term infants in most cases.69
Ventricular Septal Defects
Ventricular septal defects are the most common form of congenital heart disease detected in infancy, accounting for more than 30% of the total cases of congenital heart diseases. The incidence of ventricular septal defects is approximately 2 per 1000 live births. The spectrum of ventricular septal defects seen in prenatal life is very different from that manifesting postnatally. Isolated ventricular septal defects constituted only 6% of a large series of congenital heart diseases identified prenatally. Ventricular septal defects are commonly associated with other cardiac defects as part of more complex disease. Ventricular septal defects can vary in location and are divided into inlet, outlet, perimembranous, and muscular defects. Perimembranous ventricular septal defects account for 80% of ventricular septal defects. Outlet ventricular septal defects account for 5% of ventricular septal defects worldwide but 20% in East Asia. Inlet ventricular septal defects account for 5%, and muscular ventricular septal defects account for 10% to 20% of ventricular septal defects.7 Outlet defects are associated with aortic valve dysfunction and require surgery.70
In the fetus, the right and left ventricular pressures are equal or similar. Small dynamic differences cause systolic left-to-right and diastolic right-to-left shunting through a large ventricular septal defect. After birth, the pulmonary artery pressure drops, and the shunt through a large ventricular septal defect increases in magnitude. Pulmonary resistances continue to fall postnatally reaching its nadir at 3 to 4 months of age, when the worst symptoms of cardiac heart failure can be expected.
Ventricular septal defects are the most common lesion in many chromosomal syndromes, including trisomy 13, trisomy 18, and trisomy 21 groups, as well as in more rare syndromes. A multifactorial cause has been proposed in which interaction between hereditary predisposition and environment results in the defect.
Ventricular septal defects are the most common type of congenital heart malformation to be overlooked in the fetus; however, most of the overlooked defects tend to be small. Their detection prenatally depends on the image quality, the size, and the site of the defect, and the color Doppler capabilities of the ultrasound machine. Ventricular septal defects are commonly found as a part of complex cardiac anomalies, some of which are not obvious when the study is performed during pregnancy. Important associated defects with ventricular septal defect are coarctation of the aorta, atrial septal defects, aortic stenosis, mitral valve anomalies, pulmonary stenosis, anomalous muscle bundle of right ventricle, and anomalies of pulmonary venous return. In the 4-chamber view of a normal heart, the ventricular septum should appear intact. However, if the ultrasound beam is parallel to the ventricular septum, dropout can often be seen at the crux of the heart where the septum is thin and membranous. A real defect has edges, a so-called "T artifact," ie, bright spots delineating the borders of the defect, whereas in dropout, the ventricular septum "fades" toward the crux of the heart. Ventricular septal defects are commonly associated with other cardiac defects as part of more complex disease.
In the color flow image, a "smear" across the septum may give a false-positive diagnosis of a ventricular septal defect. Color flow projection must be seen to breech the septum to confirm a real ventricular septal defect. Bidirectional color flow across the defect (unless there is right or left ventricular outflow obstruction) confirms the presence of a real defect (Figure 6-26). Color flow mapping does not "highlight" a small ventricular septal defect by showing turbulent flow in the same way as it does postnatally, because of equal ventricular pressures in the fetus.
Color Doppler in a 25-week gestational age fetus with a muscular ventricular septal defect (arrow) between the right ventricle (RV) and left ventricle (LV). Note that the ventricular septal defect shunt is detected in diastole when the ventricles are filling.
Serial antenatal fetal echocardiography studies should be performed at 6- to 8-week intervals to assess the size of the defect and compare it with the aortic root size serially. At each visit, a renewed search is made for possible developing associated cardiac lesions, such as coarctation of the aorta. In an outlet ventricular septal defect, pulmonary stenosis can appear later in pregnancy, as evidenced by a pulmonary artery smaller than the aorta, thus evolving into tetralogy of Fallot or pulmonary valve stenosis. The size of the ascending aorta and transverse aortic arch should be monitored because hypoplasia of the aortic arch can develop in association with a ventricular septal defect as pregnancy advances. Size and function of both ventricles and the size of the aortic valve annulus should be evaluated. Development of heart failure would not be expected in this condition.
What to Expect after Delivery
If the fetus remains well compensated and the lesion is isolated, delivery can be normal at term in a secondary care center. Once the baby is delivered, an echocardiogram should be performed, within the first 2 weeks of delivery, to determine the size, number, and hemodynamics of the ventricular septal defects and to exclude additional pathology.
There have been some reports of ventricular septal defects closing spontaneously in prenatal life. The majority of ventricular septal defects usually close in the first year of life or before school age, although later closure has been reported. Smaller defects and perimembranous or muscular defects are more likely to close spontaneously.
Children with small ventricular septal defects are asymptomatic and have excellent long-term prognosis. Neither medical therapy nor surgery is indicated.
Surgical repair of ventricular septal defects is usually performed if there is failure to thrive, congestive heart failure resistant to medical therapy, pulmonary hypertension at 6 to 12 months, or cardiomegaly at school age, suggesting significant shunt. Long-term survival following repair of isolated ventricular septal defect is 86% to 93% at 12 to 15 years following repair.71
An atrial septal defect occurs in about 1 in 1500 live births. It is a common component of complex disease. In fetal life there is always a defect in the secundum portion of the atrial septum, the foramen ovale. The foramen ovale represents a normal interatrial communication that is present throughout fetal life. Functional closure of the foramen ovale occurs during the first year of life, as pressure in the left atrium exceeds that in the right atrium. In 25% to 30% of people, however, anatomic closure does not occur, and a potential interatrial channel persists through which blood or air may shunt whenever pressure in the right atrium exceeds that in the left atrium.72
The septum primum, which is the first septum to develop, is an incomplete thin-walled partition in which the anteroinferior free edge is above the atrioventricular canal and becomes lined by tissue derived from the superior and inferior endocardial cushions. Before the resultant interatrial opening (ostium primum) becomes sealed by endocardial cushion tissue, programmed cell death in an area near the anterosuperior aspect of the septum primum creates small cribriform perforations. These perforations coalesce to form a large, second interatrial communication (ostium secundum) maintaining interatrial blood flow.
At this time, to the right of the first septum, an anterosuperior infolding of the atrial roof occurs and forms a second septal structure (septum secundum). It expands posteroinferiorly as a thick-walled muscular ridge to form an incomplete partition that overlies the ostium secundum. As atrial septation is accomplished, septum secundum forms the limbus of the fossa ovalis and septum primum forms the valve of the fossa ovalis. There are essentially 4 types of atrial septal defects, with different mechanisms underlying their formation: secundum atrial septal defect, sinus venosus atrial septal defect, coronary sinus venosus, and primum atrial septal defect. It is usually sporadic, but it can occur as part of genetic syndromes such as Holt-Oram syndrome (autosomal dominant). In 1997, Li et al73 reported that Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Further understanding of genetic abnormalities causing atrial septal defects is still in its early stages. To date, heterozygous mutations in 2 genes, NKX2.5 and GATA4, have been identified to be causative for a subset of familial atrial septal defect through genetic linkage analysis of pedigrees with nonsyndromic congenital cardiovascular diseases.74,75 Most recently, a missense mutation in myosin heavy chain 6 (on chromosome 14q12) has been found to cause familial atrial septal defect.76
Normally, the foramen ovale defect occupies about the middle one-third of the atrial septum. A true secundum atrial defect is larger than the normal foramen for gestational age (3 mm in size at 20 weeks to 8 mm at term). In a true secundum defect, the atrial defect should be above this normal range. This is a rare diagnosis in the fetus. The primum atrial septal defect is characterized by a defect in the lower atrial septum with a cleft mitral valve; the sinus venosus atrial septal defect by a deficiency in the posterosuperior atrial septum; and the coronary sinus atrial septal defect by a communication at the level of the orifice of the coronary sinus. Absence of septum primum and atrial septum primum aneurism in the fetus is consistent with a secundum atrial septum defect (defect at fossa ovalis).
Color-flow imaging allows the blood traversing an atrial septal defect to be demonstrated.
In cases of isolated atrial defect, delivery should be at term and does not require a tertiary care center.
Amniocentesis should be recommended with the diagnosis of primum atrial septal defect because of the possible association with trisomy 21, followed by DiGeorge syndrome and Ellis-van Creveld syndrome. For primum atrial septal defect, spontaneous intrauterine death and neonatal death have been reported, especially with left atrial isomerism.
What to Expect after Delivery
A prospective echocardiographic study suggested that as many as 24% of newborns have evidence of an opening (3 to 8 mm) in the atrial septum in the first week of life.77 However, by a little more than 1 year of age, 92% of the patients were found to have spontaneous closure of the opening, and in most patients there was evidence of a valvelike opening of the atrial septum that was believed to contribute to closure.
In the absence of atrial isomerism, the prognosis for all forms of atrial septal defect is good.
Small secundum defects commonly close spontaneously in the first 2 years of life.77 Most of the larger defects can be closed using the transcatheter closure device by 2 to 3 years of life. Otherwise, open-heart surgery is performed around 3 to 5 years of age. It appears that spontaneous closure, or a decrease in size, is most likely to occur in atrial septal defects less than 7 to 8 mm and with younger age at diagnosis. Ostium primum and sinus venosus defects do not close spontaneously. The presence and severity of functional limitation among patients with atrial septal defects seem to increase with age. Congestive heart failure is found rarely in the first decades of life, but it can become common once the patient is older than 40 years of age. The onset of atrial fibrillation or, less commonly, atrial flutter can be a hallmark in the course of patients with atrial septal defects. The incidence of atrial arrhythmias increases with advancing age. Pulmonary vascular disease can occur in 5% to 10% of patients with untreated atrial septal defects, predominantly in females, and usually it occurs after 20 years of age.78
Atrioventricular Septal Defect
Atrioventricular canal accounts for 4% to 5% of congenital heart disease, an estimated occurrence of 0.19 in 1000 live births.79 In a large fetal echocardiography experience, atrioventricular septal defects were the most common anomaly detected, constituting 18% of abnormal fetal hearts.58
Failure of the endocardial cushions to fuse creates a defect in the atrioventricular septum. The primum atrial septal component of this defect is usually large. This results in downward displacement of the anterior mitral leaflet to the level of the septal tricuspid leaflet. In atrioventricular septal defects, the atrioventricular valves have the same septal insertion level in contrast to the leaflet arrangement in the normal heart. The distance from the cardiac crux to the left ventricular apex is foreshortened, and the distance from the apex to the aortic valve is increased.
Because the dextrodorsal conus cushion contributes to the development of the right atrioventricular valve and the outflow tracts lie adjacent to their respective inflow tracts, atrioventricular septal defects may be associated with conotruncal anomalies. In addition, shift of the atrioventricular valve orifice may result in connection of the valve primarily to only 1 ventricle, creating disproportionate or unbalanced ventricles. Berg et al80 found an association of atrioventricular septal defects with chromosomal anomalies in 52.4% (mainly trisomy 21), heterotaxy syndromes in 29.3%, nonchromosomal malformation syndromes in 6.9%, isolated complex cardiac malformations in 6.5%, singular extracardiac malformations in 2.0%, and 2.8% were isolated atrioventricular septal defects.
With isolated atrioventricular septal defects the recurrence risk is approximately 5%. The recurrence risk following a baby with trisomy 21 depends on the mother's age. If the mother is older than 35 years, the recurrence risk is the mother's age-related risk, whereas if the mother is younger than 30 years, the recurrence risk is about 1%.30
In utero diagnosis of an atrioventricular septal defect is readily made on routine fetal 4-chamber imaging. Dropout in the lower atrial septum or upper ventricular septum may be suggestive of the diagnosis. The septum primum is absent. There is inferior displacement of the atrioventricular valves, and attachment of a portion of the left atrioventricular (mitral) valve to the septum; therefore, the 2 separate atrioventricular valve orifices are equidistant from the cardiac apex. The distance from the cardiac crux to the left ventricular apex is foreshortened, and the distance from the apex to the aortic valve is increased. In atrioventricular septal defects, the disproportion between the 2 distances causes anterior displacement of the left ventricular outflow tract. As a result, the left ventricular outflow tract is longer and narrower than normal and produces the "gooseneck" deformity.
Follow-up is required at 4- to 6-week intervals because outflow tract obstruction can develop later in pregnancy (atrioventricular canal with tetralogy of Fallot) and atrioventricular valve regurgitation may increase in severity, increasing the risk of congestive heart failure.
Given the high possibility of chromosomal anomalies, amniocentesis should be offered.
What to Expect after Delivery
If the fetus remains well compensated and the lesion is isolated, delivery can be at term in a secondary-level center, but if there is any size discrepancy between the ventricles and the great arteries, delivery should be in a tertiary care center.
Usually heart failure develops progressively over the first 4 to 8 weeks of postnatal life, so medical treatment should be initiated. The timing of surgery ranges from 8 weeks to 3 years, depending on hemodynamic severity.
Huggon et al,81 in a series of 301 fetuses, noticed that despite some improvements in the outlook for atrioventricular septal defects diagnosed prenatally, the overall prognosis remains considerably poorer than that implied from surgical series. In this series, parents opted for termination of pregnancy in 58.5%. For the continuing pregnancies, Kaplan-Meier estimates for live birth, survival past the neonatal period, and survival to 3 years were 82% (confidence interval [CI] = 75.3% to 88.9%), 55% (CI = 46.0% to 64.3%), and 38% (CI = 27.1% to 48.6%), respectively. Fetal hydrops, earlier year of diagnosis, and atrioventricular block, as well as the presence of an atypical form of the lesion, are associated with adverse survival.82,83, and 84
Tetralogy of Fallot comprises a constellation of cardiac findings that share the following common anatomic abnormalities: a large malaligned ventricular septal defect, overriding of the aorta over the septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy.8 Incidence of tetralogy of Fallot ranges from 0.26 to 0.8 per 1000 live births. The proportion of patients with congenital heart disease who have tetralogy of Fallot ranges from 3.5% to 9%.85
Normal development of the conotruncus involves proper septation and alignment of the pulmonary and left ventricle outflow tracts above their respective ventricles. The embryologic precursors to the ventricular outflow tracts and great arteries are distal to the bulbus cordis and truncus arteriosus, respectively. The anatomic transition point, between the bulbus cordis and truncus arteriosus, coincides with the level at which the semilunar valves form from the growth and fusion of the truncal–bulbar cushions.
The anatomy seen in tetralogy of Fallot is believed to result from incomplete rotation and faulty partitioning of the conotruncus during septation. This process normally occurs by proper spatial growth and rotation of the truncal-bulbar ridges. Malrotation of these ridges results in misalignment of the outlet and trabecular septum, and consequent straddling of the aorta over the malaligned ventricular septal defect. The subpulmonic obstruction, then, is created by abnormally anterior septation of the conotruncus by the bulbotruncal ridges.
The sibling recurrence rate appears to range from 2.5% to 3% if only 1 sibling is affected, but it is likely to increase substantially if more than 1 sibling is affected. The recurrence risk may also increase if familial disease or syndromic features are present in the affected proband or relatives. The estimated recurrence risk to offspring of parents with tetralogy of Fallot is generally higher than that for siblings and ranges from 1.2% to 8.3%.11,28
Extra cardiac abnormalities in tetralogy of Fallot may occur in as many as 30% of affected infants and children. In fetal tetralogy of Fallot the incidence of extra cardiac lesions may be 50% to 60% with 25% having chromosomal abnormalities. Chromosomal abnormalities includes aneuploidy such as trisomies 21, 18, and 13, and single gene disorders, specifically microdeletion of chromosome 22 (up to 20% of infants with tetralogy of Fallot). It may also be seen in other less common syndromes and associations. Down syndrome is present in approximately 75% to 80% of those with the combination of atrioventricular septal defect and tetralogy of Fallot. Midline defects (eg, pentalogy of Cantrell, omphalocele), renal, skeletal and gastrointestinal, and central nervous system abnormalities may be found in fetal tetralogy of Fallot.29
In tetralogy of Fallot the 4-chamber view is typically normal, but often with a more leftward axis than normal. Usually a subaortic ventricular septal defect is seen in the long-axis view of the left ventricle (also known as 5-chamber view) with sweeps to the outflow tracts. There is anterior displacement of the ascending aorta resulting in the aorta overriding the ventricular septal defect (Figure 6-27A). The ascending aorta diameter is greater than the pulmonary artery with forward flow in the pulmonary artery. The ascending aorta tends to be larger than normal in size for gestation, particularly later in gestation, and blood flow onto the ascending aorta from both ventricles on color flow mapping can be seen. A gradient across the right ventricular outflow tract is usually not present as a result of the ventricular septal defect and due to fetal physiology. Absence of flow gradient in utero does not rule out pulmonary stenosis, and infundibular or subpulmonary narrowing caused by anterior ventricular septal deviation tends to be more appreciated later in gestation. With pulmonary atresia, the pulmonary arteries may rise from the reversed flow patent ductus arteriosus or from aorto-pulmonary collaterals from the aorta (Figure 6-27B).
A: Overriding aorta and ventricular septal defect is seen between the left ventricle (LV) and right ventricle (RV) in this 35-week gestational age fetus with tetralogy of Fallot and is a typical finding. B: In the case of tetralogy of Fallot with pulmonary atresia, there may be poorly developed pulmonary arteries, and collateral arteries (C) can be seen arising from the descending aorta (DAo) with power Doppler. LPA, left pulmonary artery.
Prenatal diagnosis is common and can document the important hemodynamic burden of pulmonary regurgitation in utero including the presence of hydrops in up to 20% of fetuses.
What to Expect after Delivery
In tetralogy of Fallot with pulmonary stenosis, delivery should be at term in a tertiary center in order to evaluate the degree of right ventricle outflow obstruction at birth and the risk of cyanotic spells.
In medical follow-up, considerations should be given to progressive right ventricle dilation related to pulmonary regurgitation and/or abnormal distal arterial impedance, because these hemodynamic issues may have an impact on long-term myocardial health. Children with tetralogy have some risk of important malignant rhythm disorders/ventricular tachycardia and/or sudden cardiac death after cardiac surgical repair.
In a 30-year follow-up study, excellent clinical results of surgical repair of tetralogy of Fallot have been reported.86 However, the nature of the repair leaves each patient with some degree of excessive hemodynamic burden because of residual defects, valvular abnormalities, or myocardial factors. For most patients, these abnormalities cause no clinical symptoms, although careful assessment of exercise capacity may reveal abnormal function. Furthermore, most large series include a few late deaths attributed to congestive heart failure.
Heterotaxia is the term used to describe an anomalous position of the viscera. The prevalence of heterotaxy syndromes is 1% of the neonates with symptomatic congenital heart disease.
Both right and left atrial isomerism comprise the heterotaxy syndromes. Right atrial isomerism or asplenia syndrome is associated with absence of the spleen and a tendency to bilateral right-sidedness. In left atrial isomerism or polysplenia syndrome, multiple splenic tissues with a tendency for bilateral left-sidedness are present along with interrupted inferior vena cava with azygous continuation of the inferior vena cava. Although the type and severity of cardiovascular malformations are somewhat different between the 2 syndromes, the same types of defects may be present in both conditions. In general, right atrial isomerism has more severe abnormalities of the structures. A normal heart or only minimal malformations of the heart is present in up to 25% of the patients with left atrial isomerism. Bilateral superior venae cavae is common, and anomalies of the pulmonary venous return are usually present. Single atrium, secundum atrial septal defect, and primum atrial septal defect are common. A single atrioventricular valve is common. Either a single ventricle or ventricular septal defect is usually present. Transposition of great arteries is usually present in right atrial isomerism and occasionally in polysplenia syndrome.
An X-linked recessive trait associated with the inability of the developing embryo to establish normal left-right asymmetry has been noted in right atrial isomerism. Familial heterotaxy occurs with autosomal dominant, recessive, and X-linked inheritance.87 Genes implicated in human heterotaxy include Zic3, LeftyA, Cryptic, and Acvr2B.88
In right atrial isomerism, there are noninverted ventricles with the right ventricle to the right (D-ventricular loop) and a right anterior aorta, and multiple anomalies of systemic and pulmonary venous connections. Bilateral superior venae cavae with direct connections to the atria, bilateral pulmonary venous connections (direct right and left pulmonary venous connections to the ipsilateral atrium), anomalous supracardiac pulmonary venous connections, and absent coronary sinus are typical in left atrial isomerism. Most patients have some atrioventricular valve abnormality, such as common atrioventricular inlet, but right or left atrioventricular valve atresia is also recognized. Many have an unbalanced form of ventricular septal defect, most often with left ventricular hypoplasia, but they may have tricuspid valve atresia and right ventricular hypoplasia. Some may have a single ventricle of uncertain or indeterminate morphology with a common atrioventricular inlet. Most patients with asplenia have pulmonary stenosis or atresia.
In left atrial isomerism, bilateral hepatic venous connections to the ipsilateral atrium, azygous or hemiazygous continuation of the inferior vena cava to the superior vena cava, common-inlet ventricle of right ventricular morphology, and double-outlet right ventricle are all typical anomalies. Some outstanding differences are noteworthy, including a lower incidence of associated pulmonary stenosis and a more frequent occurrence of bilateral pulmonary venous connections to the ipsilateral atria.
In right atrial isomerism, evaluations should be done every 4 to 6 weeks to monitor heart size and ventricular function, evidence of hydrops fetalis, progressive common atrioventricular valve regurgitation, size of left ventricle and pulmonary arteries, pulmonary vein growth, and flow patterns that could suggest progressive obstruction.
In left atrial isomerism, evaluations should be performed every week initially to check for heart rate; heart size and ventricular function; evidence of hydrops fetalis, eg, pericardial effusion; atrioventricular valve regurgitation; progressive aortic valve regurgitation; and bilateral outflow tract obstruction. Reassessment of the right ventricular outflow and direction of ductal and main pulmonary arterial flow is necessary.
The risk of amniocentesis is probably higher than the risk of abnormal karyotype in isomerism. Aneuploidy is extremely rare and reportable in atrial isomerism.
What to Expect after Delivery
In right atrial isomerism with complex congenital heart disease, delivery should be at term or as much as possible near term in a tertiary care center given the risk of pulmonary stenosis/ atresia and pulmonary vein obstruction. It is a ductal-dependent lesion so early initiation of PGE1 is mandatory. However, if obstruction of the pulmonary veins coexists, then increasing pulmonary perfusion may cause pulmonary edema.
In left atrial isomerism with complete heart block and complex congenital heart disease, delivery should be at term or as much as possible near term in a tertiary care center. However, if the baby is developing fetal hydrops, earlier delivery may be necessary, as long as it is possible to improve the hemodynamic condition of the fetus with delivery and intervention. Cesarean section delivery may be considered given the difficulties with fetal monitoring in fetal bradycardia.
In general, the mortality of right atrial isomerism is high, due to the complexity of the structural defects, and specifically the association with asplenia and right atrial isomerism, and spongiform cardiomyopathy. Fetal patients with left atrial isomerism have a high proportion of atrioventricular block. Long-term survival with right atrial isomerism is 13% to 40%, and with left atrial isomerism it is 14% to 52%. Nonsurvival correlates with atrioventricular block and hydrops. Many (33% to 45%) of these pregnancies are interrupted. Prenatal diagnosis conferred no survival advantage for either left atrial isomerism or right atrial isomerism.88
Persistent common arterial trunk or truncus arteriosus is an uncommon congenital cardiovascular malformation. There is not a striking gender difference in frequency, although most series contained more male than female subjects.
The embryonic truncus arteriosus lies between the conus cordis proximally and the aortic sac and aortic arch system distally. Partitioning of the truncus arteriosus is intimately associated with conal and aortopulmonary septation. When conotruncal or truncoaortic septation does not proceed normally, truncus arteriosus may result and is characterized by a single arterial vessel that arises from the base of the heart and gives origin to the coronary, pulmonary, and systemic arteries. Also, either deficiency or absence of the conal (infundibular) septum produces a large ventricular septal defect. Because the conal septum also contributes to the development of the anterior tricuspid leaflet and the medial tricuspid papillary muscle, these structures may be malformed. The single truncal valve may be deformed and functionally insufficient or, less commonly, stenotic.
Truncus arteriosus usually occurs as an isolated cardiovascular malformation, although it has been reported in association with anomalies of other systems, particularly the DiGeorge or velocardiofacial syndrome.31 Maternal diabetes has been implicated as a risk factor for truncus arteriosus. The anomaly has occurred in dizygotic twins and siblings, and there is an increased incidence of cardiac malformations in relatives of children with this lesion.89
Two-dimensional echocardiogram demonstrates a large ventricular septal defect directly under the truncal valve, which may be regurgitant, stenotic, or both. The pulmonary valve is not present. A large single great artery arises from the heart—truncus (Figure 6-28)—from which the brachiocephalic vessels and branch pulmonary arteries arise. Leftward cardiac axis is suggestive. Associated cardiac defects include right-sided aortic arch (30%), absence of arterial duct (50% to 75%), and less commonly aortic arch interruption, coronary anomalies, mitral valve obstruction, and atrioventricular septal defect.
The large truncal root (Truncus) overrides the ventricular septum and the ventricular septal defect. The pulmonary arteries usually arise directly from the truncus.
Progression of the lesion during pregnancy with truncal stenosis or regurgitation can cause hydrops fetalis and fetal demise and also contributes to the mortality and morbidity of affected infants after birth. In 2 series of 1790 and 23 fetuses91 each, in utero demise was 0 or 9%, pregnancy interruption 24 or 35%, and neonatal deaths 25% or 22%, respectively.
Serial antenatal studies at 4-week intervals to assess the degree of truncal valve stenosis and regurgitation and reassess the ventricular function are indicated.
In classic truncus without any signs of heart failure, aortic interruption, or other associated malformation, delivery should be as close to term as possible and at least in an institution with neonatal intensive care support. This is because such babies are at risk for significant transient hypocalcemia and also heart failure with or without myocardial ischemia (after birth the pulmonary vascular resistance falls and steals from the coronaries).
What to Expect after Delivery
Truncus usually presents in the neonatal period. Symptoms depend on the degree of left-right shunt and the truncal valve regurgitation. Mild cyanosis (88% to 92% saturation) with a single second heart sound and a systolic ejection click should suggest truncus. Onset of symptoms of cardiac heart failure is determined by the rate with which the pulmonary vascular resistance falls and the degree of pulmonary shunting tolerated by the left heart. The presence of significant truncal valve regurgitation and/or stenosis (Figure 6-29) usually worsens the degree of heart failure as it contributes to the ventricular volume load and potentially causes coronary artery steal.
Doppler echocardiography of a fetus with truncus arteriosus. Truncal valve dysfunction such as truncal stenosis (TS) and truncal regurgitation (TR) may coexist leading to a guarded prognosis.
The actuarial survival rates were 81.7% ± 3.1%, 79.7% ± 3.2%, and 79.1% ± 3.3% at 6 months, and 1 and 18 years, respectively.92 Integrity of the truncal valve influences long-term survival. It is unknown if other factors frequent in truncus arteriosus, such as the 22q11 deletion, branch pulmonary artery stenosis, and interrupted aortic arch, affect either pre- or postnatal outcomes. Death in infancy most commonly is caused by heart failure. Without surgery, most infants die within 6 to 12 months, so surgical treatment of truncus arteriosus during infancy with a right ventricle to pulmonary artery conduit has become routine. Patients who had surgery need continued follow-up care throughout life.
D-Transposition of the Great Arteries
D-transposition of the great arteries is a lethal and relatively frequent malformation, accounting for 5% to 7% of all congenital cardiac malformations. The incidence is reported to range from 20.1 to 30.5 per 100,000 live births with a strong (60% to 70%) male preponderance.
The morphogenesis of D-transposition of the great arteries can be hypothesized to result from the abnormal growth and development of the subaortic infundibulum and the absence of growth of the subpulmonary infundibulum. The aortic valve is protruded superiorly and anteriorly by the development of the subaortic infundibulum, placing it above the anterior right ventricle. Failure of development of the subpulmonary infundibulum prevents the normal morphogenetic movement of the pulmonary valve from posterior to anterior and further results in abnormal pulmonary to mitral valve ring fibrous continuity.
The course of the fetal circulation is modified because the right side of the heart ejects blood directly into the ascending aorta, in contrast to the sequence in the normal fetus, where the right ventricle ejects essentially into the descending aorta via the patent ductus arteriosus.
Extracardiac anomalies are less frequent in infants with D-transposition of the great arteries (<10%) compared with other forms of congenital heart disease, such as truncus arteriosus (48%), ventricular septal defect (34%), or tetralogy of Fallot (31%).
The outflow assessment reveals transposition of great arteries with the aorta anterior and to the right of the pulmonary artery (Figure 6-30). There is unrestricted patent foramen ovale flow with a bidirectional shunt and a normal pulmonary venous flow pattern.
Two-dimensional echocardiogram showing discordant ventriculoarterial alignments (parallel great arteries). Right-sided (anterior) aorta (Ao) connected to right-sided (anterior) morphologically right ventricle (RV) and left-sided (posterior) pulmonary artery (PA) connected to left-sided (posterior) morphologically left ventricle (LV).
Perhaps the greatest advantage of prenatal diagnosis is the ability to deliver the infant in an obstetric facility with the expectation of cardiac disease, institution of PGE1 therapy, and prompt transfer to a specialized cardiac facility before clinical deterioration may take place.
Follow-up should occur every 4 to 6 weeks to check for the size of the left ventricle and progressive right ventricle outflow tract obstruction, as well as progressive main and branch pulmonary arteries and change in direction of ductus arteriosus flow, progressive foramen ovale restriction, and progressive ductus arteriosus constriction or spontaneous closure of the ventricular septal defect.
Both transposition of great arteries physiology and anatomy are compatible with normal fetal survival and relatively normal gestational development. The risk of amniocentesis is probably higher than the risk of abnormal karyotype in simple transposition.
In transposition of great arteries with pulmonary stenosis, delivery should be at term or as much as possible near term in a tertiary care center given the risk of foramen ovale restriction and ductus arteriosus constriction. In addition, the real degree of pulmonary stenosis after birth and after ductus arteriosus closure may be difficult to predict.
What to Expect after Delivery
After birth, the pulmonary vascular resistance falls with expansion of the lungs, and pulmonary blood flow and left atrial pressures increase in accordance with the more or less normal neonatal transitional physiology. The systemic vascular resistance increases because of removal of the low-resistance placental circulation. With transposition of great arteries, the right atrial pressures are increased, and the similarity of atrial pressures tends to keep the foramen ovale open, with resulting bidirectional shunting. A patent ductus arteriosus and unrestricted patent foramen ovale are essential for immediate neonatal survival prior to surgical correction of D-transposition of the great arteries.
Surgical correction of D-transposition of the great vessels is a procedure that at the best centers has less than 2% mortality. If the foramen ovale is recognized to be restrictive, the cardiology team can be prepared for a lifesaving immediate postnatal balloon septostomy. Bonnet's group studied a series of 130 fetuses with transposition of the great arteries and concluded that prenatal diagnosis of transposition of the great arteries reduces neonatal mortality but does not eliminate the risk of death. Assessment of the restriction of the foramen ovale and of the ductus arteriosus shortly before delivery detects a subgroup of fetuses that will need early balloon atrioseptostomy. The specificity and sensitivity of the fetal echocardiogram in predicting neonatal emergency was 84% and 54%, respectively. The specificity and sensitivity of a combination of restrictive foramen ovale and ductus arteriosus constriction were 100% and 31%, respectively.43