●   TETRALOGY OF FALLOT

Definition, Spectrum of Disease, and Incidence

Tetralogy of Fallot (TOF) is characterized by a subaortic (malaligned) ventricular septal defect (VSD), an aortic root that overrides the VSD, and infundibular pulmonary stenosis (Fig. 25.1). Right ventricular hypertrophy, which represents the fourth anatomic feature of the “tetralogy,” is typically not present prenatally. The typical form is the TOF with pulmonary stenosis, but the spectrum of TOF includes severe forms, such as TOF with pulmonary atresia and TOF with absent pulmonary valve, both of which will be discussed in more detail later in this chapter. TOF is one of the most common forms of cyanotic congenital heart disease (CHD) and is found in about 1 in 3,600 live births and accounts for 3% to 7% of infants with CHD (1–3). The classic form of TOF with pulmonary stenosis accounts for about 80% of all newborns with TOF.

Ultrasound Findings

Gray Scale

In TOF, the four-chamber view appears normal (Fig. 25.2A) unless the VSD is large and visible in this plane. TOF is typically detected in the five-chamber view, which demonstrates a perimembranous subaortic VSD with an aortic root override (4) (Figs. 25.2B and 25.3 to 25.5). This aortic override is due to a discontinuity between the interventricular septum and the medial aortic wall (so-called malalignement VSD), with a partial connection of the aorta to the right ventricle (Fig. 25.3). The aorta is thus slightly shifted to the right, a condition termed aortic dextroposition. Generally the aortic root, which receives blood from both the right and left ventricles, appears dilated, especially in the third trimester, which may provide the first hint to the presence of TOF (5). Furthermore, in TOF, the overriding aorta assumes a parallel course to the ventricular septum in contrast to the ascending aorta in a normal heart (Fig. 25.3). The diagnosis of TOF also requires the demonstration of a narrow but patent main pulmonary artery “pulmonary stenosis,” which is best demonstrated in the short-axis or the three-vessel view (Figs. 25.4 and 25.5). In some milder forms of TOF, especially in midgestation, the size discrepancy between the pulmonary trunk and the aorta may be subtle. The discrepancy in size, however, becomes more obvious with advancing gestation. Occasionally, TOF is missed on second trimester ultrasound. In general, these are mild cases, where the discrepancy of vessel diameter at this stage is not evident and the VSD not easily seen. The authors have also observed a few cases of perimembranous VSDs, diagnosed in early gestation with normal-sized great vessels. With advancing gestation, these VSDs became more malaligned and the preferential flow toward the ascending aorta resulted in discrepant great vessel diameters, developing into mild forms of TOF.

Color Doppler

Color Doppler facilitates the demonstration of VSD (shunting of blood across the VSD) and confirms the presence of an overriding aorta with blood draining from both ventricles into the aortic root (Fig. 25.6). Color Doppler at the three-vessel-trachea view can also demonstrate a small pulmonary artery (Figs. 25.7 and 25.8). Often, the inflow into the aorta appears aliased on color Doppler due to the high perfusion (Fig. 25.6). Color and pulsed Doppler velocities in the pulmonary artery are generally normal or only mildly increased in the fetus, in contrast to postnatal findings (6) (Figs. 25.8 and 25.9). Flow across the ductus arteriosus is antegrade in mild TOF, but can also be reversed in more severe cases (Fig. 25.9). In such cases, postnatal ductus dependency of the pulmonary circulation can be associated with cyanosis of the newborn. Fetal echocardiography along with color Doppler can differentiate various subgroups of TOF as shown in Table 25.1.

MAPCAs, major aortopulmonary collateral arteries; RV, right ventricle; VSD, ventricular septal defect.

Early Gestation

In the late first and early second trimesters, the diagnosis of TOF is possible but in many cases difficult. Clues to the diagnosis include a large aortic root in the five-chamber view on gray scale and color (Fig. 25.10) and/or a small pulmonary artery (Fig. 25.11). The aortic override may not be easily detected. A deviation of the cardiac axis (Fig. 25.11A) may be a first hint for the presence of a cardiac malformation (7). The discrepant size between the aorta and pulmonary artery with antegrade flow in both vessels on color Doppler is an important sign at this early gestation (Figs. 25.10 and 25.11). A strong association between an increased nuchal translucency measurement and the diagnosis of TOF was reported, even in the absence of chromosomal abnormalities, with almost half of the cases in one study showing this association (8).

Three-Dimensional Ultrasound

The tomographic mode applied to a three-dimensional (3D) volume acquired at the level of the four-chamber view allows the demonstration of the VSD, aortic overriding, and the stenotic pulmonary artery in a single view of multiple planes (Fig. 25.12). Surface mode increases the spatial demonstration of aortic override (Fig. 25.13). Spatiotemporal image correlation (STIC) with color Doppler displayed in glass-body mode provides a clear demonstration of the aortic override (Fig. 25.14A) and the lesion in the three-vessel-trachea view with a narrow pulmonary artery when compared to the aorta (compare Fig. 25.14B with Fig. 15.20C).

Associated Cardiac and Extracardiac Findings

Associated cardiac abnormalities can be found in TOF. On prenatal ultrasound, the common findings include a right aortic arch, found in up to 25% of the cases. Occasionally, an atrioventricular septal defect coexists with TOF, and this increases the risk of chromosomal abnormalities (9). A patent foramen ovale or an atrial septal defect has been reported in 83% and a persistent left superior vena cava in 11% of newborns with TOF (10). Variations in coronary artery anatomy are occasionally seen, which may have an impact on the surgical approach to repair (11).

Conversely to neonates and infants with diagnosed TOF, the fetus with this cardiac anomaly tends to have a higher incidence of extracardiac malformations, chromosomal anomalies, and genetic syndromes (8). Associated extracardiac congenital anomalies are fairly common with no specific organ involvement. The rate of chromosomal abnormalities is around 30%, with trisomies 21, 13, and 18 accounting for the majority of cases (8). The rate of deletion 22q11 is found in 10% to 15% of fetuses and neonates with TOF (12, 13). The risk of deletion 22q11 in cases of TOF increases when the thymus is hypoplastic (14, 15), the aortic arch is right sided, extracardiac anomalies are noted, or polyhydramnios is found (16). Table 25.2 lists common cardiac and extracardiac abnormalities associated with TOF. TOF can also be found in syndromic diseases, such as Alagille syndrome, CHARGE syndrome (17), and many others. In recent years, there has been an uptake in the use of subchromosomal analysis (microarray) in such complex cardiac malformations, in order to assess for the presence of deletions and duplications (see Chapter 4).

Differential Diagnosis

Differential diagnosis of TOF includes conditions presenting with an overriding of the aorta, such as pulmonary atresia with VSD, absent pulmonary valve, common arterial trunk (CAT), double outlet right ventricle, and malaligned VSD without great vessels abnormalities. The diagnosis of these abnormalities can be typically achieved by the correct evaluation of the size and origin of the pulmonary trunk, and Table 25.3 lists various diagnostic tools in the differential diagnosis of these cardiac lesions.

Prognosis and Outcome

Serial prenatal ultrasound examinations to document fetal pulmonary artery growth and flow across the ductus arteriosus are critical for counseling and appropriate care of the newborn, as pulmonary artery growth has been shown to be variable and unpredictable (6, 18). In general, prenatally diagnosed cases of TOF have a worse prognosis than postnatal cases due to an increased association with chromosomal aberrations, associated syndromes, or complex extracardiac anomalies (8). Case series and analysis of cardiac surgery databases suggest a short- and long-term survival of infants with TOF upward of 90% (19, 20). Poor prognostic signs include decelerated growth of the pulmonary artery, accelerated growth of the ascending aorta, cessation of forward flow through the pulmonary valve, and reversed flow through the ductus arteriosus (6). Prenatal echocardiographic markers that could predict the need for neonatal intervention in fetuses with right ventricular outflow tract obstruction were recently reviewed in several studies. In a study of 52 fetuses with right ventricular tract outlet obstruction, a pulmonary valve/aortic valve ratio of <0.6 or a pulmonary valve Z-score of −3 at fetal final echocardiogram was highly sensitive (92%) but poorly specific (50%), whereas classifying direction of flow in the ductus arteriosus as either normal (all pulmonary-to-aorta) or abnormal (aorta-to-pulmonary or bidirectional) was both highly sensitive (100%) and specific (95%) for predicting the need for a neonatal intervention (21). In a study involving 23 live-born fetuses with isolated TOF, pulmonary valve peak systolic velocity (PVPSV) ≥87.5 cm/s at 19 to 22 weeks predicted early neonatal intervention with 100% sensitivity and 93.3% specificity (22). Furthermore, a PVPSV at 34 to 38 weeks of ≥144.5 cm/s predicted all cases undergoing early neonatal intervention (22). TOF with an atresia of the pulmonary valve (pulmonary atresia with VSD) or cases of absent pulmonary valve are acknowledged to have a worse prognosis. Table 25.4 lists poor prognostic signs associated with TOF.

PA, pulmonary artery; DA, ductus arteriosus; TGA, transposition of great arteries.

Stay updated, free articles. Join our Telegram channel

Join