CHAPTER 11 • The Fetal Heart and Great Vessels. First Trimester Ultr

 CHAPTER 11 • The Fetal Heart and Great Vessels

NTRODUCTION

Fetal cardiac examination in the first trimester focuses in general on the evaluation of

body situs, the four chambers, and the great vessels in order to confirm normal anatomy

and to rule out complex congenital heart defects (CHDs). Many CHDs can be detected

in the first trimester and are discussed in this chapter. First trimester ultrasound

evaluation of the fetal heart can also assess for the presence of indirect markers such as

tricuspid regurgitation (TR), abnormal cardiac axis, or an aberrant right subclavian

artery (ARSA), which can be clues to CHD or fetal aneuploidy. Ultrasound examination

of the fetal heart and great vessels can be a challenge in the first trimester as it requires

high-resolution images in two-dimensional (2D) gray scale and color Doppler and often

needs a combined transabdominal and transvaginal approach. In this chapter,

embryology of the fetal heart is first presented along with normal fetal cardiac anatomy

by ultrasound. Various fetal cardiac malformations that can be detected in the first

trimester are then presented. For a more comprehensive discussion on the sonographic

cardiac examination technique and a wide range of normal and abnormal fetal hearts,

we recommend our textbook “Practical Guide to Fetal Echocardiography: Normal and

Abnormal Hearts.”1

EMBRYOLOGY

The spectrum of congenital cardiac malformations is wide and is better understood with

a basic knowledge of cardiac embryology.

Starting in the third week postconception, clusters of angiogenic cardiac precursor

cells develop in the lateral splanchnic mesoderm and migrate anteriorly toward the

midline to fuse into a single heart tube. Heart tube pulsations are first recognized around

day 21 to 22 postconception (day 35 to 36 menstrual age, end fifth gestational week).

The heart develops according to well-defined major steps, namely (1) the formation of

the primitive heart tube; (2) the looping of the heart tube; and (3) the septation of atria,

ventricles, and outflow tracts (Fig. 11.1). The primitive heart tube is anchored caudallyby the vitello-umbilical veins and cranially by the dorsal aortae and pharyngeal arches,

and shows transitional folding zones such as the primary fold at the arterial pole and the

atrioventricular (AV) ring at the venous pole (Fig. 11.1). These transitional zones later

form the cardiac septa and valves. Figure 11.1 illustrates these developmental steps.1

With looping and bulging, the primitive ventricle moves downward to the right, whereas

the primitive atrium moves upward and to the left behind the ventricle. Within this tube

and at different sites, septations occur to differentiate the two atria, two ventricles, two

AV valves, and two separate outflow tracts. The paired branchial arteries with two

aortae progressively regress, resulting in a left aortic arch with its corresponding

bifurcations. On the venous side, different paired veins regress and fuse to develop the

systemic venous system with the hepatic veins and superior and inferior venae cavae.

The primitive atrium is divided into two by the formation of two septa, the septum

primum and the septum secundum. Both septa fuse except for the foramen primum,

which remains patent and becomes the foramen ovale with blood shunting from the right

to the left atrium. The formation of the ventricular septum is more complex and consists

of the fusion of septae of different spatial cardiac regions (interventricular septum, inlet

septum, and conal septum), thus explaining that ventricular septal defects (VSDs) are by

far the most common cardiac abnormalities (isolated and combined). The separation of

the outflow tracts involves a spiral rotation of nearly 180 degrees, leading to the

formation of a spiral aortopulmonary septum. This septum, resulting from the complete

fusion of both bulbus and truncus ridges, separates the outflow tract into two arterial

vessels, the aorta and pulmonary artery. Because of the spiraling of this septum, the

pulmonary artery appears to twist around the ascending aorta. The bulbar development

is responsible for incorporating the great vessels within their corresponding ventricle.

In the right ventricle, the bulbus cordis is represented by the conus arteriosus, which is

the infundibulum and in the left ventricle the bulbus cordis forms the walls of the aortic

vestibule, which is the septo-aortic and mitral-aortic continuity.1 For more details on

cardiac embryogenesis, we recommend monographs and review articles on this

subject.1–4Figure 11.1: Frontal views of the different stages of the developing heart: in A

the primitive heart tube stage, in B cardiac looping stage and in C view of the

looped heart during septation of atria, ventricles and great vessels. A: Two

transitional zones are identifiable: the atrioventricular ring (AVR) forming the

future atrioventricular valves and the primary fold (PF) forming the future

interventricular septum. B: The cardiac tube starts to loop with folding along the

long axis and rotation to the right and ventral, resulting in a D-looped heart.

Primitive cardiac chambers are better identified and are separated by

transitional zones as the sinoatrial ring (SAR), the AVR, and the PF. C: After

looping, several transitional zones can be identified separating the primitive

cardiac chambers, the AVR between the common atrium (blue) and common

ventricle (red), the PF between the primitive left (LV) and right (RV) ventricle,

and the VAR in the conotruncus (CT) region of the outflow tract of the heart.

RA, right atrium; LA, left atrium.

NORMAL SONOGRAPHIC ANATOMY AND

EXAMINATION TECHNIQUE

The steps for the examination of the fetal heart in the first trimester are no different from

the cardiac examination in the second and third trimesters. It is recommended to follow

a systematic step-by-step segmental approach to cardiac imaging. Although in the

second trimester the screening cardiac examination can be performed with gray-scale

ultrasound alone, in the first trimester, gray-scale ultrasound should be complemented

by color Doppler, especially for the evaluation of the great vessels.1 2D ultrasound

imaging with high resolution can now be achieved with transabdominal linear or

transvaginal transducers. In our experience, the transvaginal ultrasound approach is

recommended when the fetus is in transverse position low in the uterus, which providesfor the closest distance from the transvaginal transducer to the fetal chest (see Chapter

3). Furthermore, the transvaginal approach is helpful in fetuses at less than 13 weeks of

gestation or in the presence of suspected cardiac malformations.

The basic approach to fetal cardiac imaging by ultrasound is first performed in grayscale 2D ultrasound, with a focus on the fetal situs and the apical and transverse views

of the four-chamber heart (4CV) (Fig. 11.2). Ultrasound system optimization for the

gray-scale cardiac examination in the first trimester is shown in Table 11.1 . Although

the fetal abdomen and the 4CV can be reliably imaged in gray scale in the first trimester,

the anatomic orientation of the right and left ventricular outflow tracts is not commonly

seen in fetuses at less than 14 weeks of gestation because of their small size. We

therefore recommend the use of color or high-definition (power) Doppler as an adjunct

to gray-scale imaging for cardiac evaluation in the first trimester. Color Doppler in the

first trimester is therefore mostly used to indirectly evaluate the shape and size of

cardiac chambers and great vessels. The optimization of color Doppler is summarized

in Table 11.2 . Color Doppler application at the level of the four-chamber view (Fig.

11.3) is an important step for identifying normal and abnormal cardiac anatomy,

especially for fetuses at less than 14 weeks of gestation. Color Doppler demonstration

of the upper transverse views in the chest including the three-vessel-trachea (3VT) and

the transverse ductal views (Fig. 11.4) is essential for imaging of the great vessels and

is far superior to what can be achieved by gray-scale evaluation alone. Several cardiac

abnormalities involving the outflow tracts can be recognized in the first trimester in the

3VT view. The location, size, patency, and blood flow directions of the aortic and

ductal arches are more easily recognized in the first trimester on color Doppler

ultrasound (Fig. 11.4).

All ultrasound planes recommended for cardiac anatomic evaluation in the second

and third trimesters of pregnancy can be obtained in the first trimester under optimal

scanning conditions. Based upon our experience however, visualization in the first

trimester of four essential planes—(1) the axial view of the upper abdomen, (2) the

4CV in gray scale, (3) the 4CV in color Doppler, and (4) the 3VT in color Doppler

(Fig. 11.5)—provides enough information to rule out most major cardiac malformations.Figure 11.2: Typical planes displayed in gray scale during the first trimester

cardiac examination include the visualization of the abdominal situs (A) with

stomach (asterisk) and the four-chamber view, displayed in a transverse (B) or

in an apical view (C). LV, left ventricle; RV, right ventricle; R, right; L, Left.

Table 11.1 • Optimization of the gray-scale cardiac examination in the first

trimester

Fetus in dorsoposterior position (NT-position)

Image magnified

Narrow sector width

Fetal thorax to occupy one-third of ultrasound image

High contrast image settings

Mid- to high-resolution transducers

Ultrasound insonation from apical to right lateral of the fetal heart

NT-nuchal translucency

Table 11.2 • Optimization of Color Doppler Cardiac Examination in the

First Trimester

Optimize the gray-scale image before activating color Doppler

Narrow color Doppler box

Mid-velocity color Doppler range

Mid-filter levels

Mid-to-high persistenceLow color Doppler gain

Low power output

Bidirectional color Doppler if available

Figure 11.3: Color Doppler of an apical four-chamber view at 12 weeks of

gestation by transabdominal (A) and transvaginal (B) ultrasound examination

demonstrating diastolic flow from both right (RA) and left (LA) atrium into right

(RV) and left (LV) ventricle, respectively. Note that the heart in B is displayed

with a higher resolution due to the transvaginal approach.Figure 11.4: Transvaginal ultrasound of the outflow tracts in color Doppler in a

fetus at 13 weeks of gestation showing the five-chamber view (A), the short

axis view of the right ventricle (RV) (B), and the three-vessel-trachea view (C).

Ao, aorta; LV, left ventricle; PA, pulmonary artery; SVC, superior vena cava.Figure 11.5: Four essential planes in the first trimester cardiac examination

include the plane at the abdominal circumference level (A) to visualize

abdominal situs with the stomach (asterisk) on the left side, the four-chamber

view (B) in gray scale, as well as the four-chamber view in color Doppler in

diastole (C) and the three-vessel-trachea view in color Doppler in systole (D).

LV, left ventricle; RV, right ventricle; PA, pulmonary artery; Ao, aorta; R, right;

L, Left.

CONGENITAL HEART DISEASE IN THE FIRSTTRIMESTER

Congenital heart disease (CHD) is the most common severe congenital abnormality.5,6

About half of the cases of CHD are severe and account for over half of deaths from

congenital abnormalities in childhood.5 Moreover, CHD results in the most costly

hospital admissions for birth defects in the United States.7 The incidence of CHD is

dependent on the age at which the population is initially examined and the definition of

CHD used. An incidence of 8 to 9 per 1,000 live births has been reported in large

population studies.5,6 It is generally accepted that in the first trimester of pregnancy the

prevalence of CHD is higher, as many fetuses with complex anomalies die in utero,

especially when associated with extracardiac malformations or early hydrops. One of

the poor prognostic signs of CHD is its association with extracardiac anomalies

including genetic diseases. The detection of a fetal anomaly is therefore an indication

for fetal echocardiography. Even when isolated, CHD can be associated with

aneuploidy or syndromic conditions. Prenatal diagnosis of CHD in the first trimester

allows for pregnancy counseling and provides enough time for diagnostic options and

decision-making.1 CHD can be suspected in the first trimester by the presence of

indirect signs such as a thickened nuchal translucency (NT), by the presence of

extracardiac malformations, or by the direct observation of cardiac and great vessel

anatomic abnormalities.

ASSOCIATED EXTRACARDIAC MALFORMATIONS

Cardiac anomalies are often associated with extracardiac malformations either as part

of a defined genetic disease or in isolation. Cardiac anomalies may be found in

association with brain, abdominal, urogenital, or skeletal anomalies among others. Even

if CHD appears isolated, a careful follow-up should be performed in the second

trimester to look for associated extracardiac anomalies. Either isolated or in

combination with other extracardiac anomalies, the detection of a CHD is a major hint

for a possible association with aneuploidy or other syndromic conditions. The true

incidence of CHD association with aneuploidy is unknown but more than 20% of all

CHD detected in the first trimester are associated with chromosomal numeric

aberrations. This may represent an overestimation given that a significant percentage of

CHD in the first trimester is detected after a thickened NT is diagnosed. Aneuploidies

associated with CHD in the first trimester include trisomies 21, 18, and 13, as well as

with Turner syndrome and triploidy (see Chapter 6 for more details). Other

chromosomal anomalies are possible but rather accidental. One major chromosomal

anomaly is the association with deletion 22q11, testing for which has to be offered

when invasive procedure is performed, especially when a conotruncal anomaly is

detected (see below). Deletions and duplications are more commonly detected

nowadays given the widespread use of microarray as a diagnostic test followingchorionic villous sampling when CHD is diagnosed in the first trimester. Monogenic

diseases associated with cardiac defects are usually not detected in early gestation. For

more details on genetics of cardiac anomalies, we recommend monographs and review

articles on this subject.1,8

Deletion 22q11.2 Syndrome (DiGeorge Syndrome)

Deletion 22q11.2 syndrome (also called DiGeorge syndrome or CATCH 22) is the most

common deletion in humans and is the second most common chromosomal anomaly in

infants with CHD (second to trisomy 21). It has an estimated prevalence of 1:2,000 to

1:4,000 live births.9 The acronym CATCH-22 was used to describe features of

DiGeorge syndrome to include Cardiac anomalies, Abnormal facies, Thymus

hypoplasia, Cleft palate, Hypocalcemia, and the microdeletion on chromosome 22.8

Phenotypic abnormalities include cardiac anomalies, mainly outflow tract abnormalities

in combination with thymus hypoplasia or aplasia, cleft palate, velopharyngeal

insufficiency, and dysmorphic facial features.9 Disorders of the skeleton can affect the

limbs and the spine. Mental disorders are found in 30% of the adults with this deletion.8

Diagnosis of this deletion can be achieved by fluorescence in situ hybridization (FISH)

technique or with microarray analysis. In an affected fetus or infant, the parental

examination reveals, in approximately 6%, an affected parent with subtle signs of this

syndrome with a 50% transmission to future offspring.8 Cardiac anomalies that are

found in deletion 22q11.2 syndrome primarily include conotruncal anomalies such as an

interrupted aortic arch, common arterial trunk (CAT), absent pulmonary valve

syndrome, pulmonary atresia with VSD, tetralogy of Fallot (TOF), and conoventricular

septal defects.8,10,11 The presence of a right aortic arch either in isolation or in

combination with a cardiac anomaly increases the risk for deletion 22q11.2.12 Reports

on the detection of deletion 22q11.2 in the first trimester are scarce, but in our opinion,

this is primarily due to missed diagnosis of cardiac and extracardiac abnormalities

rather than due to the inability to make the diagnosis in the first trimester. Several

ultrasound features of deletion 22q11.2 that are seen in the second trimester such as a

small thymus,10 a dilated cavum septi pellucidi,13 or polyhydramnios14 are not seen in

the first trimester. Facial dysmorphism, as another feature of deletion 22q11.2, is too

subtle to be a reliable sonographic feature, even in the second trimester. In the presence

of a first trimester cardiac or extracardiac abnormality in the fetus, genetic counseling

for invasive diagnostic testing with chorionic villous sampling or amniocentesis is

recommended and with the widespread use of microarray, deletion 22q11.2 will be

more commonly detected in early gestation. Figure 11.6 shows a fetus at 13 weeks of

gestation with deletion 22q11.2 detected with targeted FISH performed due to the

presence of polydactyly and an interrupted aortic arch seen on the first trimester

ultrasound.Figure 11.6: Fetus at 13 weeks of gestation with deletion 22q11. Note in A the

presence of a normal facial profile with normal nuchal translucency (NT). Also

note in A the presence of hexadactyly (numbers 1–6), shown in hand. In B, the

four-chamber view demonstrates a ventricular septal defect (VSD). C:

Obtained at the three-vessel-trachea view and shows an interrupted aortic arch

(IAA) (arrows). Chorionic villous sampling with targeted FISH confirmed the

suspected deletion 22q11. AAO, ascending aorta; DA, ductus arteriosus; LV,

left ventricle; PA, pulmonary artery; RV, right ventricle.

INDIRECT SIGNS OF CARDIAC ANOMALIES IN THE

FIRST TRIMESTER

Several ultrasound markers associated with an increased risk for CHD have been

described in the first trimester and are today part of the indications for an early fetal

echocardiography as listed in Table 11.3. Four of these common ultrasound markers are

discussed in the following section.

Increased Nuchal Translucency Thickness

In addition to chromosomal anomalies, several reports have noted an association

between increased NT and major fetal malformations including cardiac defects (Fig.

11.7). Prospective studies in mixed low- and high-risk screening populations showed a

sensitivity of about 21% for a NT >99th percentile. Studies on the association of NT

with CHD have shown that the prevalence of major cardiac defects increases

exponentially with fetal NT thickness, without an obvious predilection to a specific

CHD.15,16 The underlying pathophysiologic mechanism relating the presence of a

thickened NT to fetal cardiac defect is not fully understood.Table 11.3 • Suggested Indications for Fetal Cardiac Imaging in the First

Trimester

Maternal indications Increased risk for aneuploidy (including maternal or

paternal balanced translocations)

Maternal poorly controlled diabetes mellitus

Maternal cardiac teratogen exposure

Previous child with complex cardiac malformation

Fetal indications Thickened nuchal translucency

Abnormal cardiac axis

Reverse flow in A-wave of ductus venosus

Tricuspid regurgitation

Extracardiac fetal malformations

Fetal hydrops in the first trimester

Reversed A-Wave in Ductus Venosus

Under normal conditions, ductus venosus (DV) waveforms show a biphasic pattern

throughout the cardiac cycle. Abnormal DV waveform pattern is typically characterized

by an absent or reversed A-wave during the atrial contraction phase of diastole (Fig.

11.8A). This flow pattern in the first trimester has been associated with an increased

risk of aneuploidy. In chromosomally normal fetuses, abnormal DV waveforms have

also been shown to be associated with structural cardiac anomalies.17 The underlying

pathophysiologic mechanism linking the reversed DV A-wave to fetal CHD is unclear,

but an increased right atrial preload as a result of an increase in volume, pressure, or

both in CHD could be one of the underlying mechanisms. Detecting a reversed A-wave

in the DV increases the risk for the presence of CHD in the fetus.16Figure 11.7: Relationship between increased nuchal translucency (NT)

thickness and risk of congenital heart disease (CHD) based on a meta-analysis

of 12 studies. Note that the prevalence of CHD increases with increased NT

thickness. (Adapted from Clur SA, Ottenkamp J, Bilardo CM. The nuchal

translucency and the fetal heart: a literature review. Prenat Diagn.

2009;29:739–748; copyright John Wiley & Sons, Ltd., with permission.)

Tricuspid Regurgitation

TR can occur in the fetus at all gestational ages and can be transient. TR at 11 to 13

weeks of gestation is a common finding in fetuses with trisomies 21, 18, and 13, and in

those with major cardiac defects.16 TR is found in about 1% of euploid fetuses, in 55%

of fetuses with trisomy 21, in one-third of fetuses with trisomy 18 and trisomy 13, and in

one-third of those with complex cardiac defects.18 A standardized approach to the

diagnosis of TR is important and includes the following (see also Chapter 1): the image

is magnified, an apical four-chamber view of the fetal heart is obtained, pulsed-wave

Doppler sample volume of 2.0 to 3.0 mm is positioned across the tricuspid valve, and

the angle to the direction of flow is less than 30 degrees from the direction of the

interventricular septum. A TR is thus diagnosed when it is seen for at least half of

systole with a velocity of over 60 cm per second. The detection of TR (Fig. 11.8B)

increases the risk for the presence of a complex cardiac defect.Figure 11.8: A: Pulsed Doppler of ductus venosus (DV) in a fetus at 13 weeks

of gestation with a cardiac defect, showing reversed flow in the A-waves (open

circle) during atrial contractions. The presence of this pattern suggests an

increased risk for associated cardiac abnormalities. B: Pulsed Doppler of the

tricuspid valve (long arrow) in a fetus with a tetralogy of Fallot. Note the

presence of tricuspid regurgitation on pulsed Doppler (opposing arrows). The

presence of tricuspid regurgitation increases the risk for the presence of

cardiac abnormalities. S, peak systolic velocity; D, peak diastolic velocity.

Cardiac Axis in Early Gestation

Several studies have established an association between an abnormal cardiac axis and

CHD in mid-second and third trimesters of pregnancy and also recently in early

gestation. Cardiac axis measurement in the first trimester can be challenging and

requires the use of high-definition color in order to clearly delineate the ventricular

septum (Fig. 11.9). In a case–control study design, we have recently reported on the

fetal cardiac axis in 197 fetuses with confirmed CHD between 11 0/7 and 14 6/7 weeks

of gestation, matched with a control group.19 In the control group, the mean cardiac axis

was 44.5 ± 7.4 degrees and did not significantly change in early pregnancy.19 In the

CHD group, 25.9% of fetuses had cardiac axis measurements within normal limits.19 In

74.1%, the cardiac axis was abnormal. The performance of cardiac axis measurement indetection of major CHD was significantly better than enlarged NT, TR, or reversed Awave in DV used alone or in combination.19

COMMON FETAL CARDIAC ANOMALIES

In the following sections, we will present CHD that can be diagnosed in the first

trimester of pregnancy. For each fetal cardiac abnormality, we will define the

abnormality, describe sonographic findings along with optimal planes for diagnosis in

the first trimester, and briefly list associated cardiac and extracardiac malformations.

Table 11.4 lists abnormal ultrasound findings and corresponding cardiac anomalies in

the first trimester of pregnancy. For more detailed information on prenatal cardiac

imaging and CHD in the first, second, and third trimesters of pregnancy, we refer the

readers to our book on this subject.1

Hypoplastic Left Heart Syndrome

Definition

Hypoplastic left heart syndrome (HLHS) is a group of complex cardiac malformations

involving significant underdevelopment of the left ventricle and the left ventricular

outflow tract, resulting in an obstruction to systemic cardiac output. In general, two main

classic forms of HLHS can be observed in the first trimester: one form involves atresia

of both the mitral and aortic valves, with practically no communication between the left

atrium and left ventricle and a nearly absent or severely hypoplastic left ventricle (Fig.

11.10A), and the other form involves a visible left ventricle, with hyperechoic wall,

globular shape, and poor contractility in association with severely dysplastic mitral

valve combined with a severe aortic stenosis or aortic atresia (Fig. 11.10B). The

reported birth incidence of HLHS is 0.1 to 0.25 per 1,000 live births.6

Ultrasound Findings

In HLHS, the four-chamber view appears abnormal in gray scale and in color Doppler.

Cases with a combined mitral and aortic atresia show an absent left ventricle, and can

be detected at 12 to 13 weeks of gestation (Figs. 11.11A and 11.12A). In gray scale, the

left ventricle appears small or absent in the 4CV (Figs. 11.11A and 11.12A), and color

Doppler shows an absence of flow into the left ventricle (Figs. 11.11B and 11.12B).

The classic appearance of a single ventricle on gray scale and color Doppler in the first

trimester is thus suggestive of HLHS. When suspected on the 4CV in the first trimester,

HLHS should be confirmed in the 3VT view, which reveals an enlarged pulmonary

artery with a small aortic arch with reverse flow on color Doppler (Figs. 11.11C and

11.12C). An echogenic globular left ventricle can occasionally be seen in the first

trimester in HLHS (Fig. 11.13) and represents left ventricular changes (fibroelastosis),

similar to that noted in the second and third trimesters of pregnancy. Of note is that the

presence of a “normal” four-chamber view in the first trimester cannot rule out HLHS,

as it has been shown to develop between the first and second trimesters of gestation.Figure 11.9: Cardiac axis (blue arrows) measurement in two fetuses at 13

weeks of gestation in color Doppler. In fetus A with a normal heart anatomy,

the cardiac axis is normal. In fetus B with an atrioventricular septal defect

(AVSD) and ventricle disproportion with aortic coarctation (CoA), the cardiac

axis is deviated with a wide angle. Cardiac axis is measured in a four-chamber

view of the heart by the angle of two lines; the first line starts at the spine (S)

posteriorly and ends in mid-chest anteriorly, bisecting the chest into two equal

halves, the second line runs through the ventricular septum. RV, right ventricle;

LV, left ventricle; L, left.

Table 11.4 • Abnormal Ultrasound Findings and Suspected Cardiac

Anomalies in the First Trimester

Four-chamber view in

gray scale and color

Doppler

Abnormal cardiac axis (left-sided in TOF, CAT—

mesocardia in TGA, DORV, dextrocardia in

heterotaxy)

Severe tricuspid insufficiency in Ebstein anomaly

Single ventricle in AVSD, univentricular heart, HLHS,

tricuspid atresia with VSD

Ventricle disproportion in coarctation of the aorta,

HLHS, HRHS, pulmonary atresia with VSD, mitral

atresia and tricuspid atresiaThree-vessel-trachea

view in color Doppler

Discrepant great vessel size with forward flow in the

small vessel in TOF, coarctation of the aorta,

Tricuspid atresia with VSD

Discrepant great vessel size with reversed flow in

the small vessel in HLHS, HRHS, PA with VSD

Single large great vessel in CAT, PA with VSD

Single great vessel of normal size in TGA or DORV

Interrupted aortic isthmus in interrupted aortic arch

Aortic arch right-sided to the trachea in right-sided

aortic arch with left ductus arteriosus, right-sided

aortic arch with right ductus arteriosus, and double

aortic arch

TOF, tetralogy of Fallot; CAT, common arterial trunk; TGA, transposition

of the great arteries; DORV, double outlet right ventricle; AVSD,

atrioventricular septal defect; HLHS, hypoplastic left heart syndrome; VSD,

ventricular septal defect; HRHS, hypoplastic right heart syndrome; PA,

pulmonary atresia.

Figure 11.10: Schematic drawings of hypoplastic left heart syndrome (HLHS).

Note in A the typical features of hypoplastic hypokinetic left ventricle (LV),

dysplastic mitral valve, atretic aortic valve, and hypoplastic aorta (Ao). B: The

infrequent type of HLHS in the first trimester with dilated, hyperechogenic left

ventricle (fibroelastosis), narrowing at the aortic valve level and obstruction to

left ventricular outflow, in association with critical aortic stenosis. RA, right

atrium; RV, right ventricle; PA, pulmonary artery; LA, left atrium.

Associated MalformationsHLHS is associated with a 4% to 5% incidence of chromosomal abnormalities,20 such

as Turner syndrome, trisomies 13 and 18, and others, and when HLHS is suspected in

the first trimester, counseling with regard to genetic testing should be performed.

Extracardiac malformations have been reported in 10% to 25% of infants with HLHS21

with associated genetic syndromes, such as Turner syndrome, Noonan syndrome, Smith–

Lemli–Opitz syndrome, and Holt–Oram syndrome.21 Fetuses with HLHS may develop

growth restriction in the late second and third trimesters of pregnancy probably due to a

20% reduction in combined cardiac output.22 When HLHS is diagnosed in the first

trimester, follow-up ultrasound examinations are recommended.

Figure 11.11: Hypoplastic left heart syndrome in a fetus at 13 weeks of

gestation demonstrated by transabdominal ultrasound. Note in A the absence

of a left ventricle (arrow) in the four-chamber view. In B, color Doppler shows

diastolic flow between right atrium (RA) and right ventricle (RV) with absent left

ventricular flow. In C, three-vessel-trachea view in color Doppler shows

antegrade flow in the pulmonary artery (PA) (blue arrow) and retrograde flow

into the aortic arch (AoA) (red arrow). LA, left atrium.Figure 11.12: Hypoplastic left heart syndrome in a fetus at 13 weeks of

gestation demonstrated by transvaginal ultrasound (different fetus than in Fig.

11.11). Note in A the absence of a left ventricle (LV) in the four-chamber view.

In B, color Doppler shows diastolic flow between right atrium (RA) and right

ventricle (RV) with absent left ventricular flow. In C, three-vessel-trachea view

in color Doppler shows antegrade flow in the pulmonary artery (PA) and

retrograde flow into the small aortic arch (AoA). Note the increased resolution

in the ultrasound images as compared to Figure 11.11 obtained

transabdominally. Compare with Figure 11.11. LA, left atrium.Figure 11.13: Four-chamber view in a fetus with hypoplastic left heart

syndrome (HLHS) at 13 weeks of gestation with gray-scale (A) and color

Doppler (B) imaging. Note the presence in A of a relatively small echogenic left

ventricular (LV) cavity. Color Doppler in B shows absence of mitral inflow

during diastole. The presence of an echogenic LV is unusually found in HLHS in

the first trimester in comparison with the second trimester. RA, right atrium;

RV, right ventricle; LA, left atrium.

Coarctation of the Aorta

Definition

Coarctation of the aorta (CoA) involves narrowing of the aortic arch, typically located

at the isthmic region, between the left subclavian artery and the ductus arteriosus (Fig.

11.14). CoA is a common anomaly, found in about 5% to 8% of newborns and infants

with CHD.6,23 CoA can be classified as simple when it occurs without important

intracardiac lesions and complex when it occurs in association with significant

intracardiac pathology.Figure 11.14: Schematic drawing of coarctation of the aorta. See text for

details. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle;

PA, pulmonary artery; Ao, aorta.

Ultrasound Findings

The presence of ventricular disproportion with a small left ventricle in the first

trimester is one of the markers for the presence of CoA. In gray scale, the ventricular

disproportion can be best demonstrated in a transverse view of the heart (Fig. 11.15).

Color Doppler demonstrates a difference in ventricular filling in the 4CV by showing

increased flow across the right ventricle when compared with the left ventricle (Fig.

11.15B). The diagnosis of CoA is confirmed in the 3VT by revealing a small aortic arch

in comparison with the pulmonary artery (Fig. 11.16). Typically, the aortic arch shows

antegrade flow in CoA (Fig. 11.16B), which enables its distinction from HLHS where

reversal flow is demonstrated on color Doppler (Fig. 11.12C). When the aortic arch

does not appear to be continuous with the descending aorta, the diagnosis of an

interrupted aortic arch should be suspected. It has to be borne in mind that confirming

the presence of CoA in the second trimester is critical because ventricular

discrepancies found in the first trimester of pregnancy may resolve with advancing

gestation. Making an accurate diagnosis of CoA is difficult in the first trimester and

commonly leads to false-positive diagnoses.

Associated MalformationsThe most common associated cardiac abnormalities in complex CoA include large

VSD, bicuspid aortic valve, aortic stenosis at the valvular and subvalvular levels,

mitral stenosis, and persistent left superior vena cava.24,25 These associated cardiac

abnormalities are difficult, if not impossible, to see on the first trimester ultrasound.

Chromosomal abnormalities are commonly associated with CoA, with Turner syndrome

representing the most common abnormality.26 If CoA is suspected in the presence of

other findings such as cystic hygroma and/or early fetal hydrops, Turner syndrome

should be considered in the diagnosis. CoA can also be found in association with other

chromosomal aberrations, such as trisomy 13 or trisomy 18, especially in the presence

of multiple extracardiac malformations. The presence of CoA with tachycardia,

impaired fetal growth, and/or multiple structural anomalies is suggestive of trisomy 13.

Figure 11.15: Four-chamber views in two fetuses (A and B) at 13 weeks of

gestation with suspected aortic coarctation. The axial gray-scale four-chamber

view in A and the apical color Doppler four-chamber view in B are abnormal

and show discrepant ventricular chamber size with a diminutive left ventricle

(LV). RV, right ventricle; L, left; R, right; LA, left atrium; RA, right atrium.

Pulmonary Atresia with Intact Ventricular Septum

Definition

Pulmonary atresia with intact ventricular septum (PA-IVS) is a group of cardiac

malformations having in common absent communication between the right ventricle and

the pulmonary arterial circulation (pulmonary atresia) in combination with an intact

ventricular septum. The right ventricular cavity is either hypoplastic with thickenedright ventricular myocardium (Fig. 11.17), or dilated with significant tricuspid valve

regurgitation and a dilated right atrium. A hypoplastic right ventricle occurs in the

majority of cases.27 PA-IVS is a rare condition with a prevalence of 0.042 to 0.053 per

1,000 live births.28

Figure 11.16: Color Doppler at the level of the four-chamber view (A) and

three-vessel-trachea view (B) in a fetus with coarctation of the aorta at 14

weeks of gestation. A diminutive left ventricle (LV) is noted in the four-chamber

view (A), and a small aortic arch is noted in the three-vessel-trachea view (B).

RV, right ventricle; RA, right atrium; LA, left atrium; PA, pulmonary artery.Figure 11.17: Schematic drawing of pulmonary atresia with intact ventricular

septum (PA-IVS). See text for details. RA, right atrium; RV, right ventricle; LV,

left ventricle; LA, left atrium; Ao, aorta; PA, pulmonary artery.

Ultrasound Findings

PA-IVS can be suspected in the first trimester with the detection of a small hypoplastic,

hypokinetic right ventricle at the 4CV (Fig. 11.18A). The anatomic depiction of the right

ventricle is similar to that of the left ventricle in HLHS. In most cases, this finding is

supported by color Doppler showing lack of right ventricular filling in the 4CV (Fig.

11.18B) and reverse flow in the ductus arteriosus and pulmonary artery in the 3VT view

(Fig. 11.18C). Often the dysplastic tricuspid valve is insufficient, and valvular

regurgitation can be demonstrated with color and pulsed Doppler.

Associated Malformations

One of the major associated findings in hearts with PA-IVS and hypoplastic right

ventricles is an anomaly of the coronary circulation, namely ventriculo-coronary arterial

communication, found in about one-third of cases of PA-IVS but typically not seen in

early gestation. Other associated cardiac findings include right atrial dilation, tricuspidvalve abnormalities, subvalvular obstruction of the aortic valve, atrial septal defects,

dextrocardia, and transposition of great arteries. Sequential evaluation into the second

trimester should be performed to rule out the association with heterotaxy, especially

with situs abnormalities. Extracardiac anomalies may be found but without an organspecific pattern. Chromosomal aberrations such as trisomy 21 or 22q11 microdeletion

are rare.

Figure 11.18: Four-chamber view in gray scale (A), color Doppler (B), and

three-vessel-trachea view (C) in a fetus with pulmonary atresia with intact

ventricular septum (PA-IVS) at 13 weeks of gestation. A: Gray scale of a

diminutive right ventricle (RV) with bulging of the interventricular septum into the

left ventricle (LV). B: Diastole in color Doppler in the absence of diastolic flow

into the right ventricle. C: The three-vessel-trachea view in color Doppler

indicates the typical pattern of antegrade flow in the aortic arch (Ao) (blue

arrow) in comparison with the retrograde flow across the ductus arteriosus

(DA) into the pulmonary artery (PA) (red arrow). RA, right atrium; LA, left

atrium.

Tricuspid Atresia with Ventricular Septal Defect

Definition

Tricuspid atresia with ventricular septal defect (TA-VSD) is characterized by the

absence of the right AV connection, resulting in lack of communication between the right

atrium and ventricle. The right ventricle is therefore diminutive in size. An inlet-type

VSD, typically perimembranous, is always present, and the size of the right ventricle isrelated to the size of the VSD. A large interatrial communication, in the form of a

widely patent foramen ovale or atrial septal defect, is necessary given an obstructed

tricuspid valve. TA-VSD is classified into three types based on the spatial orientation

of the great vessels.29 TA-VSD type 1 occurs in 70% to 80% of cases and is associated

with normally oriented great arteries. TA-VSD type 2 occurs in 12% to 25% of cases

and is associated with D-transposition of the great vessels. TA-VSD type 3, an

uncommon malformation, is seen in the remainder of TA cases and usually denotes

complex great vessel abnormalities such as truncus arteriosus or L-transposition. TAVSD is rare, with an incidence of 0.08 per 1,000 live births30 Figure 11.19 represents a

schematic drawing of type 1 TA-VSD.

Figure 11.19: Schematic drawing of tricuspid atresia with ventricular septal

defect (TA-VSD). See text for details. RA, right atrium; RV, right ventricle; LV,

left ventricle; LA, left atrium; Ao, aorta; PA, pulmonary artery.

Ultrasound Findings

TA-VSD can be detected in the first trimester on gray scale and color Doppler of the

4CV. Typically an enlarged left ventricle and a hypoplastic right ventricle is noted on

gray scale at the 4CV and color Doppler on transabdominal ultrasound reveals what

appears to be a single ventricular heart. With high-resolution transabdominal and

transvaginal transducers, the hypoplastic right ventricle is seen and the VSD is shown

with blood flow from the left to the right ventricle (Fig. 11.20A). In type 1 TA-VSD at

the 3VT view, the pulmonary artery is smaller than the aorta with antegrade flow in both

great arteries (Fig. 11.20B). TA-VSD has been associated with an enlarged NT in thefirst trimester.31 Because reversed A-wave in the DV has been reported in the second

and third trimesters in association with TA-VSD, this finding may be present in the first

trimester and may represent an early sign of right atrial increased preload.32

Figure 11.20: Transvaginal ultrasound of tricuspid atresia with ventricular

septal defect (TA-VSD) in color Doppler in a fetus at 13 weeks of gestation. A:

Obtained at the four-chamber view and shows blood inflow through the mitral

valve into the left ventricle (LV), with blood reaching the right ventricle (RV)

through the VSD (arrow). B: The three-vessel-trachea view with a narrow

pulmonary artery (PA) (associated pulmonary stenosis) as compared to the

aorta (Ao). LA, left atrium; RA, right atrium.

Associated Malformations

Associated cardiac findings include a large interatrial communication such as a patent

foramen ovale or an atrial septal defect, a VSD, transposition of the great vessels, and

various degrees of right ventricular outflow obstruction. Extracardiac anomalies can

also be found and fetal karyotyping should be offered despite a rare association with

chromosomal aberration including 22q11 microdeletion.33

Atrioventricular Septal Defect

Definition

Atrioventricular septal defect (AVSD) represents a cardiac abnormality characterized

by a deficient AV septation and abnormalities of the AV valves, primarily resulting in

the presence of a common AV junction. Common synonyms to AVSD include AV canal

defect or endocardial cushion defect. In the complete form of an AVSD, there is a

combination of an atrial septum primum defect and an inlet VSD with an abnormal

common AV valve, which connects to the right and left ventricles (Fig. 11.21). The

common AV valve usually has five leaflets. Partial AVSD includes an atrial septumprimum defect and a cleft in the mitral valve with two distinct mitral and tricuspid valve

annuli that attach at the same level on the interventricular septum. Partial AVSD is

difficult to detect in the first trimester. AVSDs can also be classified as balanced or

unbalanced. In unbalanced AVSD, the AV connection predominantly drains to one of the

two ventricles, resulting in ventricular size disproportion. Unbalanced AVSD is

typically found in association with heterotaxy syndrome. AVSDs are common cardiac

malformations found in 4% to 7.4% of all infants with CHD.34

Figure 11.21: Schematic drawing of a four-chamber view with a complete

atrioventricular septal defect (AVSD). LA, left atrium; RA, right atrium; LV, left

ventricle; RV, right ventricle.

Ultrasound Findings

AVSD may be recognized in the first trimester by demonstrating the defect in the center

of the heart during diastole on gray-scale ultrasound at the 4CV (Fig. 11.22A). In an

apical insonation of the 4CV in systole, the linear insertion of the AV valves can be

seen, albeit quite difficult in the first trimester. Color Doppler reveals the classic single

channel of blood flow entering the common AV (Figs. 11.22B and 11.23) instead of two

distinct channels over the tricuspid and mitral valves as is shown in normal hearts (Fig.

11.3). Occasionally, the defect is so large that the image resembles a univentricular

heart. A typical finding is the presence of valve regurgitation on color Doppler at the

common AV valve (Fig. 11.24). Often a thickened NT is found in association with

AVSD and this combination suggests the presence of trisomy 21 or trisomy 18. The

combination of AVSD with heart block or a right-sided position of the stomach raises

the suspicion of isomerism and heterotaxy syndrome.Figure 11.22: Apical four-chamber views in diastole in gray scale (A) and color

Doppler (B) in a fetus with complete atrioventricular septal defect (AVSD) at 12

weeks of gestation. AVSD is demonstrated by the star in A and B. Note the

presence in B of a single channel of blood on color Doppler entering the

ventricles over a common atrioventricular valve. LV, left ventricle; RV, right

ventricle.Figure 11.23: Apical four-chamber views during diastole in color Doppler in two

fetuses with complete atrioventricular septal defect (AVSD) at 12 weeks of

gestation. AVSD is demonstrated by the star in A and B. Note the presence in

diastole of a single channel of blood entering the ventricles over a common

atrioventricular valve. LA, left atrium; RA, right atrium; LV, left ventricle; RV,

right ventricle.

Associated Malformations

Associated cardiac abnormalities in AVSD include TOF, double outlet ventricle, right

aortic arch, and other conotruncal anomalies. Extracardiac anomalies in AVSD

primarily include chromosomal abnormalities, mainly trisomy 21 and much less

commonly trisomies 18 and 13. About 40% to 45% of children with Down syndrome

have CHD and of these, 40% are AVSD, commonly of the complete type. 34 Antenatal

diagnosis of AVSD, when isolated, is associated with trisomy 21 in 58% of cases. 35

When AVSD is associated with heterotaxy, the risk of chromosomal abnormality is

virtually absent, but the outcome is worsened due to the severity of the cardiac and

extracardiac malformations.

Ventricular Septal Defect

Definition

VSD is an opening in the ventricular septum, leading to a hemodynamic communication

between the left and right ventricles. VSDs are common CHDs, second only to bicuspid

aortic valve.36 Typically VSDs are reported based on their anatomic locations on theseptum. In prenatal series, muscular VSDs are most common and account for about 80%

to 90%, with perimembranous VSDs being the second most common.37 VSDs are

frequently associated with various cardiac anomalies.

Ultrasound Findings

VSDs are generally too small to be reliably detected as isolated anomalies in the first

trimester. Caution should be made in diagnosing VSDs in early gestation given a

significant false-positive diagnosis resulting from echo dropout in 2D ultrasound and

color overlapping when using color Doppler. In most cases, the VSD is reliably

demonstrated when it is associated with another cardiac anomaly (Fig. 11.25A) or when

the four-chamber view anatomy is abnormal. The presence of blood flow shunting

across the VSD confirms its presence in the first trimester (Fig. 11.25B). When a VSD

is suspected but cannot be confirmed in the first trimester, a follow-up examination is

recommended after 16 weeks of gestation with careful evaluation of the ventricular

septum.

Figure 11.24: A–C: Four-chamber views in color Doppler and during systole in

three fetuses with complete atrioventricular septal defect at 12, 13, and 14

weeks, respectively. Note the presence of valve regurgitation (faint arrows)

across the common atrioventricular valve in the three fetuses. LV, left ventricle;

RV, right ventricle.Figure 11.25: A: A five-chamber view in a fetus with tetralogy of Fallot at 13

weeks of gestation. Note the presence of a perimembranous ventricular septal

defect (VSD). B: A transverse four-chamber view in color Doppler at 12 weeks

of gestation with a muscular VSD. Note the presence of blood flow across the

VSD documented by color Doppler. LV, left ventricle; RV, right ventricle; Ao,

aorta.

Associated Malformations

Associated cardiac anomalies are common and are typically diagnosed prior to the

diagnosis of VSD in the first trimester. The association of an extracardiac abnormality

with a VSD increases the risk for the presence of a syndrome or chromosomal

aberration. VSDs are the most common abnormalities in many chromosomal defects,

such as trisomies 21, 18, and 13.36 An isolated muscular VSD has a risk of

chromosomal abnormalities similar to that of normal pregnancy.37

Ebstein Anomaly

Definition

In Ebstein anomaly, the septal and posterior leaflets of the tricuspid valve are displaced

inferiorly from the tricuspid valve annulus, toward the apex of the heart, and originate

from the right ventricular myocardium (Fig. 11.26). The anterior tricuspid leaflet

maintains its normal attachment to the tricuspid valve annulus. The proximal portion of

the right ventricle is then continuous with the true right atrium and forms an “atrialized”

portion of the right ventricle (Fig. 11.26). The spectrum of Ebstein anomaly is wide and

varies from a minor form, with minimal displacement of the tricuspid valves with mild

TR, to a severe form, with the “atrialization” of the entire right ventricle. Ebstein

anomaly is one of the less common cardiac abnormalities occurring in about 0.5% to1% of CHD in live births.6

Figure 11.26: Schematic drawing of Ebstein anomaly. See text for details. LA,

left atrium; RA, right atrium; LV, left ventricle; RV, right ventricle.

Ultrasound Findings

Ebstein anomaly is detected in the first trimester by the presence of significant TR.

Other main findings of Ebstein anomaly such as cardiomegaly and a dilated right atrium

are typically seen later in gestation. The displaced apical attachment of the tricuspid

valve in the right ventricle can be seen on gray-scale ultrasound in an apical or axial

4CV (Fig. 11.27A). Severe TR originating near the apex of the RV can be clearly

demonstrated on color and pulsed Doppler (Fig. 11.27B and C). In severe Ebstein

anomaly in the first trimester, the presence of cardiomegaly may be associated with a

thickened NT and fetal hydrops, a sign of impending fetal demise. Although some severe

cases of Ebstein anomalies may be suspected in the first trimester, mild Ebstein cases

can be missed and only detected in the second trimesters of pregnancy. The presence of

significant TR in the first trimester can be a marker of Ebstein anomaly, which is

typically confirmed in the second trimester of pregnancy.

Associated Malformations

Associated cardiac abnormalities include an obstruction of the right ventricular outflow

tract as pulmonary stenosis or atresia in more than 60% of fetuses diagnosed with

Ebstein anomaly prenatally.38 Atrial septal defect, which is not evident in the first

trimester, represents another common association and has been reported in up to 60% of

children with Ebstein anomaly. Most cases of Ebstein anomaly are isolated findings, butan association with chromosomal anomalies, such as trisomy 21 or trisomy 13, has been

reported in addition to familial cases. Long-term complications of Ebstein include

pulmonary hypoplasia in neonates and rhythm disorders in children.

Univentricular Heart

Definition

Univentricular heart or univentricular AV connection describes a group of cardiac

malformations where the AV connection is completely or predominantly to a single

ventricular chamber. Embryologically, this malformation is thought to result from failure

of the development of the bulboventricular loop stage. From a clinical point of view, a

CHD with a univentricular heart describes a heart with one functioning ventricle with

inflow from one or both atria. Within univentricular heart, three subgroups can be

identified: double inlet, where two atria connect to a single ventricle through two patent

AV valves; single inlet, where one atrium connects to a single ventricle through a single

AV valve; and common inlet, where both atria connect to a single ventricle through a

single AV valve. The morphology of the ventricle is generally a left ventricular

morphology with a rudimentary right chamber. Figure 11.28 represents a schematic

drawing of a univentricular heart with double inlet ventricle.

Figure 11.27: Gray scale (A) and color (B) in a fetus at 13 weeks of gestation

with Ebstein anomaly. Note the presence of generalized hydrops (asterisks) in

A and B. The displaced apical attachment of the tricuspid valve in the right

ventricle (RV) is shown in A (arrow). Severe tricuspid regurgitation originating

near the apex of the RV is shown in B (arrow). C: Pulsed Doppler of the

regurgitant jet across the dysplastic tricuspid valve. RA, right atrium; LV, leftventricle; L, left.

Figure 11.28: Schematic drawing of double inlet univentricular heart. See text

for details. LA, left atrium; RA, right atrium.

Ultrasound Findings

The detection of a univentricular heart in the first trimester is fairly common, not

because the condition itself is common, but rather because several severe cardiac

anomalies appear as a single ventricle on gray scale and color Doppler. Interestingly,

the classic univentricular heart is rarely detected in the first trimester and as shown in

Figure 11.29, this anomaly commonly escapes detection given the presence of two

inflow streams on color Doppler. Given the small size of the first trimester fetal heart,

several cardiac malformations such as HLHS, tricuspid atresia, mitral atresia, large

AVSD, and severe CoA may present as a single ventricle heart, especially on

transabdominal scanning with color Doppler (Figs. 11.11, 11.12, and 11.22). When a

single ventricle heart is suspected on color Doppler in the first trimester, a thorough

evaluation of the fetal heart with transvaginal ultrasound is recommended in order to

delineate the specific cardiac abnormality. It is preferred in such situations to examine

the fetal heart on transvaginal ultrasound in gray scale first and to assess in detail the

anatomy of the cardiac chambers and great vessels before switching to color Doppler.

Figure 11.30 shows other cardiac malformations that were initially suspected as

univentricular hearts on color Doppler evaluation.

Associated Malformations

Associated malformations in univentricular heart are atresia, hypoplasia, or straddlingof the AV valves, pulmonary (or subpulmonic) outflow obstruction, aortic (or subaortic)

outflow obstruction, and conduction abnormalities, primarily due to the anatomic

disruption of the conduction system.39 Many of these associated cardiac malformations

may not be evident or are difficult to detect in the first trimester of pregnancy.

The most important extracardiac abnormality to rule out is the presence of right or

left isomerism, especially in the presence of a common inlet ventricle.40 Chromosome

anomalies and other extracardiac anomalies are possible but rather unusual.

Figure 11.29: Fetus at 14 weeks of gestation with a double inlet univentricular

heart. Note that on gray-scale ultrasound (A) and color Doppler (B), both right

(RA) and left atrium (LA) drain through two atrioventricular valves into a single

ventricle (SV). Interestingly, in color Doppler (B), this can be easily

misdiagnosed as two-ventricular heart. L, left.Figure 11.30: Abnormal apical four-chamber views in color Doppler in three

fetuses (A–C) with cardiac anomalies suspicious for a “univentricular heart” at

12 to 13 weeks of gestation. In fetus A, a single chamber (right ventricle) is

perfused on color Doppler in a case of hypoplastic left heart syndrome (arrow

points to the absent left ventricle). Fetus B shows flow into one ventricle, which

is the left ventricle (LV), with absence of diastolic flow into the hypoplastic right

ventricle (RV) in a fetus with pulmonary atresia and dysplastic tricuspid valve. In

fetus C, a defect is seen in the center of the heart (star) (single color channel)

in a case of a large atrioventricular septal defect. RA, right atrium; LA, left

atrium.

Heterotaxy Syndrome, Atrial Isomerism, and Situs Inversus

Definition

Heterotaxy Syndrome (in Greek, heteros means different and taxis means arrangement)

is a general term that is used to describe the complete spectrum of abnormal organ

arrangement.41 The term right and left atrial isomerism (in Greek, iso means same and

meros means turn) has been suggested and used in heterotaxy syndrome as the atrial

morphology best describes organ arrangement.42 Isomerism of the thoracic organs is

characterized by a rather symmetric arrangement of the otherwise asymmetric structures

including the atria and lungs,43 thus allowing a classification into two main groups:

bilateral left-sidedness, also called left atrial isomerism and bilateral right-sidedness,

also called right atrial isomerism. Heterotaxy syndrome including right and left atrial

isomerism is found in between 2.2% and 4.2% of infants with CHD.6

Situs inversus is defined as a mirror-image arrangement of the thoracic and

abdominal organs to situs solitus (normal anatomy). Partial situs inversus can be either

limited to the abdominal organs and is generally called situs inversus with levocardia

or limited to the chest and is called dextrocardia.Ultrasound Findings

Right and left isomerism can be detected in the first trimester, owing to a thickened NT

in combination with cardiac anomaly or in the presence of hydrops with complete heart

block.43,44 Abnormal situs on ultrasound in the first trimester may represent the first clue

to the presence of right or left isomerism (Figs. 11.31 and 11.32). The cardiac axis can

be shifted thus revealing a suspicion for the presence of cardiac abnormality (Fig.

11.31).19 The presence of complete heart block in the first trimester should raise

suspicion for left atrial isomerism, as Sjögren antibodies are not typically associated

with bradyarrhythmia before 16 weeks. The detection of AVSD and univentricular heart

is feasible in the first trimester and the suspicion of such an anomaly, especially in

combination with a right-sided stomach, should suggest the presence of heterotaxy (Fig.

11.31). The arrangement of the abdominal vessels either as juxtaposition of the aorta

and inferior vena cava (right isomerism) or as interruption of the inferior vena cava

with azygos continuity (left isomerism) is difficult to diagnose in the first trimester. The

addition of color Doppler, however, may assist in the diagnosis of abnormalities in the

abdominal vessels. The assessment of pulmonary venous connections is also possible

but rather difficult in early gestation.

Partial and complete situs inversus can be detected in the first trimester. The

transvaginal approach to determining fetal situs may be challenging given the difficulty

inherent in the transvaginal probe orientation. Suspected situs abnormalities should be

confirmed at a later gestation.

Associated Malformations

Associated cardiac malformations are numerous in heterotaxy and primarily include

AVSD and univentricular heart. Associated extracardiac anomalies in heterotaxy are

typically not detected in the first trimester and include various gastrointestinal

anomalies and extrahepatic biliary atresia.45

Associated cardiac anomalies in situs inversus are on the order of 0.3% to 5% and

include VSD, TOF, double outlet right ventricle (DORV), and complete or corrected

transposition of the arteries.1 The presence of primary ciliary dyskinesia has also been

demonstrated in patients with heterotaxy and patients with complete situs inversus.46

Interestingly, chromosomal aberrations such as trisomies are nearly absent in this group.Figure 11.31: Transverse views of the fetal chest (A) and abdomen (B) in a

fetus at 13 weeks of gestation with isomerism, first suspected by the

discrepant positions of the heart in the left chest (A) and the stomach (St) in the

right abdomen (B). Note the presence of an abnormal cardiac axis and an

abnormal four-chamber view in A. L, left; R, right.

Tetralogy of Fallot

Definition

TOF is characterized by a subaortic (malaligned) VSD, an aortic root that overrides the

VSD, and infundibular pulmonary stenosis (Fig. 11.33). Right ventricular hypertrophy,

which represents the fourth anatomic feature of the “tetralogy,” is typically not present

prenatally. TOF with pulmonary stenosis is the classic form, but the spectrum of TOF

includes severe forms, such as TOF with pulmonary atresia and TOF with absent

pulmonary valve. TOF is one of the most common forms of cyanotic CHD and is found

in about 1 in 3,600 live births.5 The classic form of TOF with pulmonary stenosis

accounts for about 80% of all newborns with TOF.Figure 11.32: Transverse views of the fetal abdomen (A) and chest (B) and in

a fetus at 13 weeks of gestation with isomerism, first suspected by the

discrepant positions of the heart in the right chest (dextrocardia) (A) and the

stomach (asterisk) in the left abdomen (B). L, left; R, right.Figure 11.33: Schematic drawing of tetralogy of Fallot. See text for details.

LA, left atrium; RA, right atrium; LV, left ventricle; RV, right ventricle; VSD,

ventricular septal defect; PA, pulmonary artery; Ao, aorta.

Ultrasound Findings

In its classic form, TOF may be difficult to diagnose in the first trimester. The

sonographic anatomy of the four-chamber view in TOF can appear normal in the first

trimester, unless in association with cardiac axis deviation (Fig. 11.34A and B). Clues

to the diagnosis of TOF include a large aortic root in the five-chamber view on gray

scale and color Doppler ultrasound (Figs. 11.34C and 11.35A) with a small pulmonary

artery (Figs. 11.34D and 11.35B). Although the aortic override may not be easily noted

on the five-chamber view, the small pulmonary artery can be easily detected in the 3VT

in color Doppler (Figs. 11.34D and 11.35B). The discrepant size between the aorta and

pulmonary artery in the 3VT view with antegrade flow in both vessels on color Doppler

is an important sign for TOF in the first trimester (Figs. 11.34D and 11.35B). In our

experience, TOF in the first trimester is more commonly detected by the abnormal 3VT

view than by the five-chamber view demonstrating aortic override.Figure 11.34: Tetralogy of Fallot at 14 weeks of gestation examined

transvaginally. A and B: Axial planes of the chest at the four-chamber view in

gray scale and color Doppler, respectively. In A and B, the four-chamber view

appears normal with an axis deviation to the left (A) and with normal filling

during diastole (B). C: The five-chamber view in color Doppler. Note in C

overriding of the dilated aorta over the ventricular septal defect (star). D: The

three-vessel-trachea view in color Doppler. Note in D the discrepant vessel size

with a small pulmonary artery (PA) as compared to the dilated overriding aorta

(AO). Antegrade flow is noted in both great vessels in D. LV, left ventricle; RV,

right ventricle.Figure 11.35: Tetralogy of Fallot at 13 weeks of gestation. A: An axial plane at

the level of the five-chamber view in color Doppler. Note in A, the large

ventricular septal defect (VSD) with the overriding aorta (AO). B: The threevessel-trachea view in color Doppler. Note in B the discrepant vessel size with

a small pulmonary artery (PA) as compared to the AO. Antegrade flow is noted

in both great vessels in B. LV, left ventricle; RV, right ventricle.

Associated Malformations

Associated cardiac abnormalities with TOF include a right aortic arch, found in up to

25% of the cases or occasionally, an AVSD, which increases the risk of chromosomal

abnormalities. There is a high association of TOF with extracardiac malformations,

chromosomal anomalies, and genetic syndromes.47 The rate of chromosomal

abnormalities is around 30%, with trisomies 21, 13, and 18 accounting for the majority

of cases.47 The rate of microdeletion 22q11 is found in 10% to 15% of fetuses and

neonates with TOF,48 and this risk increases in the presence of thymic hypoplasia,10,49

right-sided aortic arch, extracardiac anomalies, or polyhydramnios in the second

trimester of pregnancy.

Pulmonary Atresia with Ventricular Septal Defect

Definition

Pulmonary atresia with ventricular septal defect (PA-VSD) is characterized by atresia

of the pulmonary valve, hypoplasia of the pulmonary tract, membranous or infundibular

VSD, and an overriding aorta (Fig. 11.36). Sources of pulmonary blood flow include

the ductus arteriosus and/or systemic–pulmonary collateral circulation. Systemic–pulmonary collateral circulation typically includes collateral arteries from the

descending aorta to the lungs, called major aortopulmonary collateral arteries

(MAPCAs).50 PA-VSD has a prevalence of 0.07 per 1,000 live births.6 A 10-fold

increased risk of PA-VSD is seen in infants of diabetic mothers.6

Figure 11.36: Schematic drawing of pulmonary atresia with ventricular septal

defect (PA-VSD). See text for details. LA, left atrium; RA, right atrium; LV, left

ventricle; RV, right ventricle; PA, pulmonary artery; Ao, aorta; DA, ductus

arteriosus.

Ultrasound Findings

The presence of an abnormal cardiac axis can be the first clue for the presence of PAVSD (Fig. 11.37A). The 4CV is commonly normal in PA-VSD and the five-chamber

view shows a dilated overriding aortic root (Fig. 11.37A) with an absence of a normalsized pulmonary artery in the right ventricular outflow tract view. Color Doppler at the

3VT view shows a dilated transverse aortic arch with absence of antegrade flow across

the pulmonary artery (Fig. 11.37B). Typically color Doppler demonstrates reverse flow

in a tortuous ductus arteriosus and pulmonary artery in an oblique view of the chest,

inferior to the aortic arch. The presence of MAPCAs is not detected in the first trimester

of pregnancy.Associated Malformations

A right-sided aortic arch can be present in 20% to 50% of all cases.51 Absence of the

ductus arteriosus is also reported in about half of the cases. MAPCAs are associated in

about 44% of cases50 and are typically diagnosed in the second trimester of pregnancy.

Associated extracardiac findings include a high incidence of chromosomal aberrations.

In the Baltimore–Washington Infant Study, 8.3% of children with PA-VSD had

chromosomal anomalies.6 The incidence of 22q11 microdeletion is high and is found in

18% to 25% of fetuses with PA-VSD,50 with an increased association in the presence of

MAPCAs and/or a right aortic arch or hypoplastic thymus.

Common Arterial Trunk

Definition

CAT is characterized by a single arterial trunk that arises from the base of the heart and

gives origin to the systemic, coronary, and pulmonary circulations (Fig. 11.38). A large

VSD is almost always present in this anomaly, resulting from the near absence of the

infundibular septum.52 The spectrum of the disease is wide and is mainly related to the

anatomic origin of the right and left pulmonary arteries, which may arise from a

pulmonary trunk or as direct branches from the CAT or the descending aorta. The root

of the CAT is large and has a biventricular origin in most cases (overrides the septal

defect). In up to a third of CAT cases, however, the root appears to arise entirely from

the right ventricle and, in rare cases, entirely from the left ventricle. The CAT valve has

three leaflets (tricuspid) in about 69% of cases, four leaflets (quadricuspid) in 22% of

cases, two leaflets (bicuspid) in 9% of cases, and, on very rare occasions, one, five, or

more leaflets.53 CAT is reported to occur in about 1.07 of 10,000 births.30

Ultrasound Findings

Demonstrating the direct origin of the pulmonary arteries from the CAT is difficult in the

first trimester and is facilitated by the application of color Doppler (Fig. 11.39). A

typical feature of CAT is the presence of truncal valve regurgitation, which can help to

differentiate CAT from other cardiac malformations involving an overriding aorta. A

differentiating feature of CAT from PA-VSD is that the pulmonary arteries arise directly

from the CAT rather than the right ventricle.

Associated Malformations

Associated cardiac malformations are common with CAT. The ductus arteriosus is

absent in 50% of the cases, and when present it remains patent postnatally in about twothirds of patients.54 Aortic arch abnormalities are common with CAT, with right-sided

arch noted in 21% to 36% of cases54 (Fig. 11.39). Truncal valve dysplasia with

incompetence is a common association. Extracardiac structural malformations are seen

in up to 40% of CAT cases and are typically nonspecific (10). Numerical chromosomal

anomalies are found in about 4.5% of the cases and include trisomies 21, 18, and 13.Microdeletion 22q11 is reported in 30% to 40% of cases.55

Figure 11.37: Transvaginal ultrasound at the level of the five-chamber view (A)

and the transverse ductal arch view (B) in a fetus at 12 weeks of gestation with

pulmonary atresia and ventricular septal defect. The five-chamber view (A)

shows a large overriding aorta (AO) (star) and an abnormal cardiac axis

(dashed lines). In the three-vessel-trachea view (B), reverse flow in the ductus

arteriosus (DA) is demonstrated on color Doppler (curved arrow). RV, right

ventricle; LV, left ventricle.Figure 11.38: Schematic drawing of common arterial trunk. See text for

details. LV, left ventricle; RV, right ventricle; VSD, ventricular septal defect; PA,

pulmonary artery; Ao, aorta.

Transposition of the Great Arteries

Definition

Complete transposition of the great arteries (TGA) is a common cardiac malformation

with AV concordance and ventriculoarterial discordance. This implies a normal

connection between the atria and ventricles; the right atrium is connected to the right

ventricle through the tricuspid valve and the left atrium is connected to the left ventricle

through the mitral valve, but there is a switched connection of the great vessels, the

pulmonary artery arising from the left ventricle, and the aorta arising from the right

ventricle. Both great arteries display a parallel course, with the aorta anterior and to the

right of the pulmonary artery (Fig. 11.40), hence the term D-TGA (D = “dexter”). DTGA is a relatively frequent cardiac anomaly with an incidence of 0.315 cases per

1,000 live births.56

Ultrasound Findings

In TGA, the great vessels assume a parallel course, which can be demonstrated in an

oblique axial view of the fetal chest (Fig. 11.41B). This oblique view of the fetal chestis not a standard plane of the obstetric ultrasound examination and thus is not displayed

on routine ultrasound scanning. The demonstration on color Doppler of a single great

vessel in the 3VT is often the first clue for the presence of TGA (Fig. 11.41A) in the

first trimester. Once TGA is suspected on the 3VT view, the diagnosis can then be

confirmed in the first trimester by demonstrating the parallel orientation of the great

vessels in the oblique view of the fetal chest (Fig. 11.41B). The 4CV is commonly

normal in TGA with the exception of an abnormal cardiac axis in some cases with

mesocardia.

Figure 11.39: Common arterial trunk (CAT) in a fetus at 13 weeks of

gestation. Note in planes A and B the bifurcation of the CAT into the aorta (AO)

and the pulmonary artery (PA). Also note that the aortic arch courses to the

right of the trachea, as a right-sided aortic arch. R, right; L, left.Figure 11.40: Schematic drawing of D-transposition of great arteries (D-TGA).

See text for details. LA, left atrium; RA, right atrium; LV, left ventricle; RV, right

ventricle; PA, pulmonary artery; Ao, aorta.

Associated Malformations

VSDs and pulmonary stenosis (left ventricular outflow obstruction) are the two most

common associated cardiac findings in D-TGA. VSDs are common and occur in about

40% of cases and are typically perimembranous but can be located anywhere in the

septum.56 Pulmonary stenosis coexists with a VSD in D-TGA patients in about 30% of

cases, and the stenosis is usually more severe and complex than in D-TGA with intact

ventricular septum.56 Extracardiac anomalies may be present but rare, and numerical

chromosomal aberrations are practically absent in D-TGA. Microdeletion of 22q11

could be present and should be ruled out, especially when extracardiac malformations

or a complex D-TGA is present.

Double Outlet Right Ventricle

Definition

DORV encompasses a family of complex cardiac malformations where both great

arteries arise primarily from the morphologic right ventricle (Fig. 11.42) but differ with

regard to the variable spatial relationship of the great arteries, the location of the VSD

that is commonly seen with DORV, and the presence or absence of pulmonary and less

commonly aortic outflow obstruction. In DORV, four types of anatomic relationships ofthe aorta to the pulmonary artery at the level of the semilunar valves and four anatomic

locations for the VSD have been described.57 The exact subtype of DORV may be hard

to characterize prenatally as the position of the VSD is difficult to establish with

accuracy in fetal echocardiography. DORV has an incidence of approximately 0.09 per

1,000 live births.5

Ultrasound Findings

DORV can occasionally be diagnosed in the first trimester due to the presence of an

abnormal 4CV or 3VT view. An abnormal cardiac axis is commonly found in DORV

and can be noted in the first trimester (Fig. 11.43A and B). The 3VT view typically

shows discrepant size of the great arteries, a single large vessel (Fig. 11.43C), or

parallel orientation of the great vessels (Fig. 11.44). When the 4CV is normal, DORV is

difficult to diagnose in the first trimester.

Figure 11.41: Color Doppler ultrasound at the three-vessel-trachea view (A)

and an oblique view of the chest (B) at 12 weeks of gestation in a fetus with

complete transposition of the great arteries (D-TGA). The three-vessel-trachea

view (A) demonstrates the presence of a single great artery of normal size,

representing the superiorly located aorta (Ao). The oblique view of the chest

(B) shows the parallel course of the great vessels arising in discordance with

the aorta (AO) from the right (RV) and the pulmonary artery (PA) from the left

ventricle (LV).Figure 11.42: Schematic drawing of double outlet right ventricle. See text for

details. LA, left atrium; RA, right atrium; LV, left ventricle; RV, right ventricle;

Ao, aorta; PA, pulmonary artery; VSD, ventricular septal defect.

Associated Malformations

Associated cardiac findings are common and include a full spectrum of cardiac lesions.

Pulmonary stenosis is the most common associated malformation and occurs in about

70% of cases.58 Extracardiac anomalies are very common in fetuses with DORV and

are nonspecific for organ systems.59 Chromosomal abnormalities are frequently found in

the range of 12% to 40% in fetuses with DORV and primarily include trisomies 18 and

13 and 22q11 microdeletion.60

Right and Double Aortic Arch

Definition

Right aortic arch is diagnosed when the transverse aortic arch is located to the right of

the trachea on transverse imaging of the chest. A right aortic arch is associated with

three main subgroups of arch abnormalities: right aortic arch with a right ductus

arteriosus, right aortic arch with left ductus arteriosus, and double aortic arch (Fig.

11.45). Right aortic arch can be part of a complex cardiac malformation, but can often

also be an isolated finding.61 A right aortic arch occurs in about 1 in 1,000 of the

general population,62 but the prevalence of right aortic arch is probably higher in thepresence of other cardiac anomalies.

Figure 11.43: Four-chamber views in gray scale (A), color Doppler (B), and

three-vessel-trachea view (C) in a fetus at 13 weeks of gestation with double

outlet right ventricle. In A and B, the ventricular septal defect (VSD) is

visualized in gray scale (A) and color Doppler (B). Note the abnormal location

of the heart in the chest with mesocardia in A and B. The three-vessel-trachea

view (C) shows the aorta (AO) as a single vessel (superior to the pulmonary

artery). In this case, the AO has a course to the right of the trachea (Tr),

representing a right aortic arch. RV, right ventricle; LV, left ventricle.

Figure 11.44: Oblique views (A and B) of the fetal thorax with color Doppler in

a fetus at 13 weeks of gestation with double outlet right ventricle (same fetus

as in Fig. 11.43). Note the presence of the ventricular septal defect (VSD) in A,and the origin of the aorta (AO) and pulmonary artery (PA) from the right

ventricle (RV) in A and B. Aortic and ductal arches are seen to the right of the

trachea (Tr) in A and B. LV, left ventricle.

Figure 11.45: Schematic drawings of the three-vessel-trachea view in a normal

fetus (A) where the transverse aortic arch (Ao) and isthmus merge with the

pulmonary artery (PA) and ductus arteriosus (DA) into the descending aorta in

a ‘‘V-shape’’ configuration to the left of the trachea (T). B: A right-sided aortic

arch with a right-sided DA in a ‘‘V-shape’’ configuration to the right side of the

trachea. C: A right aortic arch with the transverse aortic arch to the right side

of the trachea; the DA is left-sided and the connection of aortic and ductal

arches constitutes a vascular ring around the trachea in a ‘‘U-shape’’

configuration. D: A rare sub-form of right aortic arch with a left DA forming a

double aortic arch with the transverse aortic arch bifurcating into a right and a

left aortic arch (LAoA) surrounding the trachea and esophagus. L, left; R, right;

SVC, superior vena cava; RAoA, right aortic arch.

Ultrasound Findings

The diagnosis of a right aortic arch is possible in the first trimester and is enabled by

the use of color Doppler at the 3VT view (Figs. 11.46 and 11.47). It is commonly

suspected on transabdominal scanning when the relationship of the transverse aortic and

ductal arches is evaluated. Transvaginal scanning can help in confirming the diagnosis.

In recent years, we were able to diagnose right aortic arch with its three subgroups in

the first trimester. Differentiating between the U-sign right aortic arch and the double

aortic arch (lambda sign) may be difficult in the first trimester (Figs. 11.46 and 11.47).

When suspected in the first trimester of pregnancy, the identification of the actual

subtype of right aortic arch can be confirmed on follow-up ultrasound examination in the

second trimester of pregnancy.

Associated Malformations

Even if the right aortic arch appears as an isolated finding on ultrasound, fetalchromosomal karyotyping should be offered to rule out chromosomal aberrations,

primarily 22q11 microdeletion12 and occasionally trisomy 21 and other aneuploidies.

Associated intracardiac anomalies are more common when the aorta and ductus

arteriosus are on the right (V-sign) than with double aortic arch or with the U-sign right

aortic arch.1 Typical cardiac anomalies observed with a right aortic arch are TOF,

pulmonary atresia with VSD, CAT, absent pulmonary valve, tricuspid atresia, and

DORV.61,63 The presence of a right aortic arch in association with a conotruncal

anomaly increases the risk of 22q11 microdeletion.61,63

Anomalies of the Systemic and Pulmonary Veins

The systemic and pulmonary veins in the first trimester are generally too small in size to

be clearly evident on gray-scale ultrasound, making detection of venous malformations

extremely difficult. Anomalies of the abdominal venous vasculature are discussed in

Chapter 12. The presence of a left persistent superior vena cava may be rarely detected

in the first trimester. Anomalies of the pulmonary venous system are still considered not

diagnosable in the first trimester, unless in combination with isomerism, which provides

a clue to the presence of anomalous pulmonary venous return. A follow-up in the second

trimester of pregnancy is recommended when pulmonary venous malformations are

suspected in the first trimester.

Aberrant Right Subclavian Artery

ARSA can be demonstrated in the first trimester in the 3VT view in color Doppler by

reducing the velocity of flow in order to demonstrate the small subclavian artery. The

ability to image the ARSA is significantly enhanced when transvaginal fetal ultrasound

is performed (Fig. 11.48). ARSA has been associated with trisomy 21 and other

aneuploidies. The patient’s prior risk for aneuploidy should be taken into consideration

when counseling is performed for the diagnosis of an isolated ARSA.

Figure 11.46: Three-vessel-trachea views in two fetuses at 13 weeks of

gestation with a right aortic arch with a left ductus arteriosus (U-sign)

demonstrated on transabdominal (A) and transvaginal (B) color Doppler. PA,

pulmonary artery; Ao/AO, aorta; SVC, superior vena cava; TR, trachea; L, left.Figure 11.47: Transvaginal ultrasound in color Doppler in a fetus at 12 weeks

of gestation with double aortic arch (A,B). Note the left (LAO) and right (RAO)

aortic arches surrounding the trachea. Differentiating a RAO (see Fig. 11.46)

from a double arch is more commonly performed in the second trimester of

pregnancy. PA, pulmonary artery; DA, ductus arteriosus.1.

2.

3.

4.

5.

6.

7.

Figure 11.48: Transvaginal ultrasound of an axial view of the fetal chest at the

three-vessel-trachea view showing an aberrant right subclavian artery (ARSA)

in two fetuses (A and B), both at 13 weeks of gestation noted during the nuchal

translucency measurement. Ao, aorta; PA, pulmonary artery; L, left

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