Congenital heart disease (CHD) is the most common severe congenital abnormality and a leading cause of infant morbidity and mortality, with an estimated incidence of about 4-13 per 1000 live births. Between 1950 and 1994, 42% of infant deaths reported to the World Health Organization were attributable to cardiac defects. Prenatal detection of CHD may improve the outcome of fetuses with specific types of cardiac lesions, but prenatal detection rates vary widely. Despite substantial advancement in ultrasound technology over the past years and increased availability of ultrasound to pregnant women, CHD remains an abnormality that is most frequently missed by prenatal ultrasonography. Of all cases of CHD, 46% are diagnosed by the first week of life, 88% by the first year of life, and 98% by the fourth year of life. CHD’s account for over half of the deaths from congenital abnormalities in childhood.
The optimal time to perform fetal heart screening is between 18 and 22 weeks’ gestation. Assessment of both the four-chamber view and outflow tracts is recommended, however, as noted in the American Institute of Ultrasound in Medicine (AIUM) practice parameter document concerning performance of the standard diagnostic obstetric ultrasound examination, the 3-vessel view and 3-vessel trachea view should be included if technically feasible. This course will primarily focus on the four-chamber view, describing both the normal anatomy and a discussion of several abnormalities. We will also review both the maternal and fetal risk factors for CHD.
Risk Factors for CHD
Risk factors for CHD can be divided into familial, maternal and fetal. Of note, the majority (80-90%) of congenital heart defects are identified incidentally (i.e. no risk factors) in low-risk pregnancies on routine antenatal screening. Thus, fetal cardiac screening in all patients is extremely important. If there is family history of CHD, assuming the etiology is not syndromic or due to a chromosomal abnormality, the risk of CHD in the fetus is increased. The risk of CHD is higher in the presence of maternal CHD as compared to CHD in the father or a sibling. Depending upon the specific family history, the approximate risk of fetal CHD is as follows:
- CHD in the mother: 3-7%
- CHD in the father: 2-3%
- CHD in a sibling: 2-6%
- CHD in two (or more) siblings: 10%
- CHD in a second or third-degree relative: low risk
Diabetes mellitus (DM) is a commonly encountered condition during pregnancy This does not include gestational diabetes which is diagnosed during pregnancy and does not confer the increased risk of congenital anomalies (including congenital heart defects). The incidence of CHD is increased fivefold in infants born to mothers with pregestational DM. Hyperglycemia is a teratogen, as an increased glycosylated hemoglobin level (HbA1c), particularly in the first-trimester is associated with an increased risk of CHD. There appears to be a linear relationship between the risk of congenital anomalies and the HbA1c level. Septal defects and conotruncal (outflow tract) malformations are among the most common defects associated with maternal DM.
Teratogens are agents that may irreversibly alter growth, structure, or function of the developing embryo or fetus. The period of organogenesis, defined as 2 to 8 weeks postconception, is a particularly vulnerable period for the developing embryo. More specifically, for the developing heart, exposure to a teratogen between 6.5 and 8 weeks’ gestation may result in an anomaly.
Another maternal metabolic disease associated with an increased risk of fetal CHD is phenylketonuria (PKU). During organogenesis, a maternal phenylalanine levels exceeding 15 mg/dL is associated with a 10- to 15-fold increase in fetal CHD. These lesions include tetralogy of Fallot, atrial and ventricular septal defects. If maternal dietary control is not achieved by 10 weeks’ gestation, there is a 12% risk of fetal CHD. Other fetal abnormalities in phenylketonurics include microcephaly and growth restriction.
Maternal ingestion of certain drugs during pregnancy has been linked to an increased risk of CHD. Alcohol is a known teratogen, responsible for a constellation of findings (fetal alcohol syndrome) that include cardiac defects. Septal defects are the most common type associated with alcohol use. Certain anticonvulsants, including phenytoin and trimethadione have been implicated in fetal CHD. Another anticonvulsant, valproic acid, is a known teratogen associated with a significantly increased risk of neural tube defects (1-2%). However, a causal relationship between valproic acid and fetal CHD has not been established. Retinoic acid, a vitamin A derivative is another known teratogen, with conotruncal defects and aortic arch abnormalities among the most common types of fetal CHD. Angiotensin-converting enzyme inhibitors, a commonly used class of antihypertensive medications may increase the risk of CHD when the fetus is exposed during the first-trimester. Atrial and ventricular septal defects are among the most common.
There are many fetal risk factors that increase the risk of CHD. Chromosomal abnormalities constitute a group that is commonly encountered in clinical practice. This includes trisomy 21, 13 and 18, with risks of fetal CHD of 40-50%, 80% and 90-100%, respectively. Turner syndrome (monosomy X or 45, X), trisomy 9 and trisomy 8 mosaicism are other examples of chromosomal abnormalities associated with fetal CHD. The most common defect associated with trisomy 21 is an atrioventricular septal defect (AVSD), also known as an endocardial cushion defect or atrioventricular (AV) canal. Trisomy 21 is the most common chromosomal anomaly seen in infants with CHD. There are also many syndromic causes of fetal CHD. DiGeorge syndrome, also known as 22q11.2 deletion syndrome or velocardiofacial syndrome, is the most common microdeletion syndrome in humans, and the second most common chromosomal anomaly in infants with CHD, with an estimated prevalence of 1:3,000 live births. Features of DiGeorge syndrome include immune deficiency, hypocalcemia, neurocognitive impairment, facial anomalies, seizures and renal anomalies. Congenital heart disease is seen in approximately 75% of cases, with conotruncal abnormalities most common. Other syndromes associated with fetal CHD include Alagille, Holt-Oram and Noonan syndrome, both autosomal dominant conditions, and Meckel-Gruber, Ellis-van Creveld and short rib-polydactyly syndrome, all autosomal recessive conditions.
The nuchal translucency (NT) measurement obtained between 11 and 13 6/7th weeks’ gestation is an effective method of individual risk assessment for chromosomal abnormalities.
An NT thickness of greater than or equal to 3.5 mm in a chromosomally normal fetus has been correlated with a prevalence of CHD of 23 per 1,000 pregnancies. All studies on the association of NT with CHD have shown that the prevalence of major cardiac defects increases exponentially with fetal NT thickness.
In 2013, updated guidelines for ultrasound screening of the fetal heart were published by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). Fetal heart screening as defined by these guidelines includes examination of the fetal upper abdomen (which helps to determine situs), the four-chamber view and outflow tracts. As we will focus on the four-chamber view in this course, the following may serve as a checklist that addresses key points as they pertain to the four-chamber view.
- The majority of the heart resides in the left hemithorax
- The heart occupies a third of the thoracic arch
- The cardiac apex points to the left
- The cardiac axis should measure 45 degrees ± 20 degrees
- The cardiac rhythm is regular
- There is no pericardial effusion present
- There are four chambers present
- Atrial chambers
o Two atria, approximately equal in size
o Foramen ovale flap in left atrium
o Atrial septum primum present near crux
o Four pulmonary veins enter left atrium
- Ventricular chambers
o Two ventricles, approximately equal in size
o Absence of ventricular wall hypertrophy
o Moderator band at right ventricular apex
o Ventricular septum intact (apex to crux)
- Atrioventricular junction and valves
o Intact cardiac crux
o Two atrioventricular valves open and move freely
o Differential offsetting: tricuspid valve leaflet inserts more apically on the ventricular septum (i.e. closer to cardiac apex) than does mitral valve
The cardiac axis is the angle formed by two lines: one drawn from the spine to the anterior chest wall, and the other drawn through the interventricular septum. A normal cardiac axis points to the left of the midline (apex leftward), with a normal angle of 45 degrees +/- 20 degrees. An abnormal cardiac axis is seen in many congenital anomalies. Left axis deviation is often noted in conotruncal (i.e. outflow tract) abnormalities, including tetralogy of Fallot and common arterial trunk. Right axis deviation may be seen in lesions such as double outlet right ventricle and atrioventricular septal defect. Figure 1 illustrates the technique for obtaining the cardiac axis.
Figure 1: Apical view of four-chamber heart demonstrating the normal cardiac axis, which is 45 degrees +/- 20 degrees. To obtain the cardiac axis, measure the angle (orange double arrow) between a straight line drawn from the spine to the anterior chest wall (yellow line) and a line drawn through the interventricular septum (red line).
Assessment of cardiac size is important in determining if cardiomegaly is present. The etiology of cardiomegaly may be cardiac or extracardiac, and table 1 lists many of these causes.
Table 1: Potential causes of fetal cardiomegaly.
The cardiothoracic ratio (CTR) is a method to objectively assess cardiac size. Either area or circumference may be used. CTR may be calculated using the following:
CTR = cardiac area (or circumference)
thoracic area (or circumference)
If the area is being used to calculate the CTR, recall the heart occupies approximately one third of the thoracic area (i.e. three fetal hearts can “fit” within the thoracic cavity), thus the normal CTR when using area should be less than 0.30-0.35. If using circumference, the normal CTR should be less than 0.5. Ideally, these measurements should be performed at the end of diastole when the atrioventricular valves are closed. Figure 2 illustrates the principles of obtaining the CTR.
Figure 2: The cardiothoracic ratio (CTR). The CTR is an objective measurement that can be used to determine if the cardiac size is normal or if cardiomegaly is present. Either the circumference or area can be used. If using circumference, a normal CTR should be less than 0.5. If using area, a normal CTR is approximately 0.3-0.35.
The morphologic right atrium forms the right and anterior part of the heart, residing to the right of the left atrium. Its anterior portion is also referred to the right atrial appendage (RAA) and is formed from course trabeculations known as pectinate muscle. The RAA is pyramidal in shape with a broad base and extends as a pouch between the superior vena cava and the right ventricle. The posterior aspect of the right atrium is smooth-walled and receives blood via the superior and inferior vena cavae (SVC, IVC) as well as the coronary sinus (CS). The SVC is responsible for drainage of blood from the head and upper extremities, and the IVC drains the lower extremities and abdomen. These systemic venous connections serve as a marker to help identify the right atrium. The CS is a thin vein 1-3 mm in size which runs along a posteriorly located groove between the left atrium and left ventricle (atrioventricular groove) and empties into the right atrium inferiorly, near the interatrial septum and slightly below the foramen ovale. The CS is part of the heart’s own venous system and receives all of the venous drainage of the coronary circulation. The CS may be identified from the apical four-chamber view with a slight posterior angulation. Figure 3 demonstrates the CS located within the left atrioventricular groove.
Figure 3: In this image, the coronary sinus (red arrow) can be seen coursing posteriorly within the left atrioventricular groove between the left atrium and left ventricle. Under normal conditions, the coronary sinus has a diameter of 1 to 3 mm, courses perpendicular to the interatrial septum, and opens into the posterior wall of the right atrium. The coronary sinus provides the venous drainage of the heart.
The sinoatrial node and atrioventricular node, important components of the cardiac conduction system are contained within the right atrium.
The morphologic left atrium is the most posterior cardiac chamber closest to the fetal spine. In the fetus, it is nearly equal in size to the right atrium. The left atrial chamber is round and has smooth walls with the exception of the left atrial appendage, which is narrow and fingerlike in shape and contains numerous pectinate muscles. Four pulmonary veins (the right and left upper pulmonary vein and right and left lower pulmonary vein) drain into its posterior wall, although on the four-chamber view, only the two lower veins can be visualized entering the left atrium, as shown in figure 4.
Figure 4: Pulmonary veins. Normally, the left atrium receives oxygenated blood from the lungs via the pulmonary veins, which are seen here (green arrows) as two slit like vascular structures entering the left atrium.
Just as systemic venous connections serve as a marker for the right atrium, these pulmonary venous connections serve as a marker for the left atrium. Abnormalities of these connections are noted in both partial and total anomalous pulmonary venous return.
The interatrial septum (IAS) separates the left and right atrium and is formed by both the septum primum and septum secundum. A third portion of the IAS is referred to as the sinus venosus which is located at the superior aspect or roof of the atria. The septum primum resides inferiorly close to the atrioventricular valves and the septum secundum forms the midportion. The foramen ovale is formed as a perforation in the septum secundum, and it functions to direct oxygenated blood from the placenta to the left atrium. The flap of the foramen ovale, also known as the primum flap or foraminal flap, is formed by the septum primum and extends into the left atrium. This flap has a wide variation in size and shape, and typically appears as a semilunar reflective membrane and is best seen using the lateral (axial) four-chamber view. In real time, the foramen ovale flap moves from the right atrium into the left atrium as the oxygenated blood from the ductus venosus (which enters the right atrium via the IVC) streams across the foramen ovale to reach the left heart. When this flap is thickened or redundant, it can lead to the presence of fetal premature atrial contractions, which is usually a benign finding. Figure 5 shows both the foramen ovale and the foramen ovale flap.
Figure 5: Apical four-chamber view showing the foramen ovale, the normal communication between the left and right atrium, the foramen ovale that shunts oxygenated blood from the umbilical vein into the left atrium. The foramen ovale flap resides in the left atrium because blood normally passes right to left across the atrial septum.
The morphologic right ventricle is the most anterior chamber visualized on a fetal echocardiogram. It is trapezoidal in shape and is made up of three portions: the inlet and apical portions, which are heavily trabeculated, and the outlet portion, which is smooth. The apical portion contains the moderator band, which is a course trabeculation that traverses the bottom third of the right ventricle. The moderator band is an important marker that identifies the right ventricle and distinguishes it from the left ventricle. Figure 6 demonstrates the moderator band lying within the right ventricle.
Figure 6: Basal four-chamber view showing the moderator band (yellow circle) which is located in the inferior portion of the right ventricle. It is a marker that defines the morphological right ventricle.
The right ventricle receives blood from the right atrium via the tricuspid valve, and the blood flows out from the pulmonary artery.
The morphologic left ventricle is conical in shape with smooth walls and fine apical trabeculations and lies posterior to the right ventricle. It receives blood from the left atrium via the mitral valve, and blood flows via the aorta. Most of the left lateral surface of the fetal heart is occupied by the left ventricle. The wall thickness and cavity size of the left ventricle is comparable to these dimensions in the right ventricle. As the workload demands on each ventricle are greater than those placed on the atria, the wall thickness of the ventricles is greater than seen in the atria. Both ventricles reach the apex of the heart (i.e. apex forming), although the right ventricle is more anterior than the left. In conditions such as hypoplastic left heart syndrome, usually only the right ventricle is apex forming.
Each ventricle is associated with its corresponding atrioventricular (AV) valve. The tricuspid valve “belongs” to the right ventricle and the mitral valve “belongs” to the left ventricle. The tricuspid valve has both septal and free ventricular wall attachments, which is in contrast to the mitral valve which lacks septal attachments and only has free ventricular wall attachments. The two AV valves are comparable in size, with the tricuspid valve slightly larger in a normal heart. Importantly, the tricuspid valve inserts more apically on the interventricular septum than does the mitral valve. This differential offset is usually 5 mm or less and is illustrated in figure 7.
Figure 7: Apical four-chamber view demonstrating the apical offset of the tricuspid valve (TV). The red line represents this differential insertion of the TV as compared to the mitral valve (MV) on the interventricular septum. Lack of offset or too much offset can be seen in certain congenital cardiac lesions.
Abnormalities of the four-chamber view are suspected when there is either a lack of offset, or too much offset. This will be discussed later in this course.
The ventricles are separated by the interventricular septum (IVS), which consists of five sections. The muscular section is the thickest and largest part of the IVS and is located near the cardiac apex. The membranous section of the IVS is thin and fibrous and located at the basal portion near the atrioventricular valves. It is not uncommon with today’s advanced ultrasound technology to detect very small muscular ventricular septal defects. The other three sections of the IVS include the inlet, outlet and apical.
Four-chamber view abnormalities
Many cardiac anomalies may be diagnosed from a detailed assessment of the four-chamber view using the principles described above. This section will discuss some of these. A more complete list is noted in table 2.
Table 2: Congenital Heart Disease Associated with an Abnormal Four-Chamber View.
Ventricular septal defect
Ventricular septal defects (VSD’s) are the most common congenital cardiac defect. Isolated VSDs account for 30% of children born with congenital heart defects and are associated with other cardiac anomalies in about 30% of cases. In the fetus, most VSD’s are classified as either muscular or membranous (also referred to as perimembranous). In prenatal series, however, muscular VSD’s are most common and account for about 80% to 90%, with perimembranous VSD’s being the second most common. Figures 8 and 9 show examples of muscular and perimembranous VSD’s.
Figure 8: Muscular ventricular septal defect (VSD). Subcostal four-chamber view that shows a VSD (yellow circle) in the muscular part of the interventricular septum (IVS) with the use of color flow Doppler. The subcostal view is optimal for assessment of a possible VSD as the ultrasound beam is perpendicular to the IVS.
Figure 9: Perimembranous VSD. Subcostal four-chamber view shows a defect in the interventricular septum in its thinnest portion near the crux of the heart.
An important concept to recognize is the possibility for ultrasound image “drop out” when assessing the membranous portion of the IVS. This is often noted on an apical four-chamber view when the ultrasound beam is parallel to the IVS. This ultrasound “drop out” may result in the overdiagnosis of a perimembranous VSD. To avoid this pitfall, obtain a subcostal (also known as a lateral) four-chamber view where the ultrasound beam is perpendicular rather than parallel to the IVS. Figures 10 illustrates this concept of ultrasound “drop out”.
Figure 10: The normal transition from the muscular to the membranous portion of the IVS may result in signal “drop out” (arrows) if the ultrasound beam is parallel to the IVS. This can result in a false impression of a VSD. If a VSD is suspected in the apical four-chamber view, adjusting the angle of insonation such that the beam is perpendicular to the IVS as noted in the subcostal view will help differentiate between a true VSD and “drop out”.
Atrioventricular Septal Defect
An atrioventricular septal defect (AVSD) is also referred to as an AV canal or endocardial cushion defect. Specifically, it is a defect in the primum atrial septum and inlet ventricular septum. This condition should be suspected when one cannot demonstrate the normal apical offset of the tricuspid valve on the IVS. Rather, there is a single valve that will form a straight line during systole. This condition is the most common heart defect seen in trisomy 21 (Down syndrome). An example of an AVSD is shown in figures 11 and 12.
Figure 11: Atrioventricular septal defect (AVSD). In this defect, the normal offset of the AV valves is absent. This image is taken during ventricular systole, when a single AV valve appears as a straight line (red arrows) across the heart.
Figure 12: AVSD during diastole. The crux of the heart is missing, giving the impression of a “hole” in the middle of the heart (as noted by the “*”). An AVSD may be classified as unbalanced if the single AV valve is committed more to one ventricle than the other.
Hypoplastic Left Heart Syndrome
Hypoplastic left heart syndrome (HLHS) refers to a group of conditions with varying degrees of hypoplasia of the mitral valve, left ventricle and aorta such that the left ventricle is unable to support the systemic arterial circulation. It constitutes approximately 3% of CHD and is more common in males. HLHS is associated with a 4% to 5% incidence of chromosomal abnormalities, and extracardiac malformations have been reported in 10% to 25% of infants with HLHS. There is also an increased risk of fetal growth restriction likely due to compromised cardiac output. As noted above, the ventricles should be approximately equal in size. When the right ventricle appears larger than the left ventricle, either the RV is too big, or the LV is too small. Another clue to the presence of HLHS is the bulging of the foramen ovale flap (primum flap) into the right atrium rather than the normal bulging into the left atrium. Figure 13 shows an example of a hypoplastic LV which is the primary feature of HLHS. Although survival has improved with the advancement of surgical techniques, many studies still suggest a high mortality (up to 45%) at 6 years of age.
Figure 13: Hypoplastic left heart syndrome (HLHS). Note the ventricular size discrepancy as the left ventricle is smaller than the right ventricle. Also note the right ventricle is completely apex forming.
Ebstein’s anomaly is an abnormality of the tricuspid valve that can be recognized during assessment of the four-chamber view. It is not particularly common, constituting 0.5% to 1% of infants born with CHD, with an equal male-to-female distribution. However, it is more common in prenatal series, accounting for 3-7% of CHD noted in fetuses. The higher number is a result of more severe cases that result in a higher fetal or early neonatal death rate. Ebstein’s anomaly has been associated with lithium use, although the actual risk remains extremely low (1 in 2500). An abnormal offset of tricuspid valve is the is key to making diagnosis of Ebstein’s anomaly. As noted by its name, the tricuspid valve has three leaflets, namely the anterior, septal and posterior. They are named as such based on their anatomic orientation in the right ventricle. Normally, these three leaflets insert near the crux of the fetal heart, which is the point between the two AV valves and the atrial and ventricular septum. In Ebstein’s anomaly, the anterior leaflet remains normally attached to the tricuspid valve annulus, the fibrous structure that anchors the valve. However, the septal and posterior leaflets are displaced inferiorly from the annulus toward the cardiac apex. With this apical displacement of the tricuspid valve hinge point, the right ventricle is said to become “atrialized” as the proximal portion of the right ventricle becomes continuous with the true right atrium
Figure 14: Ebstein’s anomaly. Note the significant apical displacement of the septal leaflet (white arrow) of the tricuspid valve resulting in “atrialization” of the right ventricle. Also note the enlarged right atrium (*). In some cases, an atrial septal defect may be present (blue arrow).
. Cardiomegaly, defined as an increase in cardiac size, if often noted during the routine obstetrical anatomic survey, and in some cases, the cardiomegaly may be massive. Pulmonary hypoplasia, which increases neonatal morbidity and mortality, can occur when severe cardiomegaly is found. A cardiothoracic area ratio of greater than 0.6 (normal less than 0.3-0.35) in fetuses with cardiomegaly is associated with the postnatal presence of pulmonary hypoplasia. The cardiomegaly is primarily due to right atrial dilation. Tricuspid regurgitation is another hallmark of this condition that may be seen with color flow Doppler.
Figure 15: Ebstein’s anomaly. Note the severe tricuspid regurgitation. Varying degrees of tricuspid regurgitation may be seen in Ebstein’s anomaly due to both TV dysplasia and leaflet malposition. When severe, there is an increased risk of fetal hydrops.
The severity of right atrial enlargement and degree of tricuspid regurgitation can vary and is dependent in part on the degree to which the tricuspid valve is apically displaced. Other cardiac defects associated with Ebstein’s anomaly include atrial septal defect and pulmonary stenosis/atresia, both of which occur in approximately 60% of children with Ebstein’s anomaly. Prognosis is poor, with prenatal series reporting a stillbirth rate of 45% and overall mortality of 80-90%.
Total Anomalous Pulmonary Venous Return
As noted above, there are four pulmonary veins of which two can be visualized draining into the left atrium on the four-chamber view. When either a portion or all of these pulmonary veins drain (directly or indirectly) into the right atrium, this entity is referred to as partial or total anomalous pulmonary venous return (TAPVR), respectively. TAPVR often escapes prenatal detection, and accounts for 2-3% of live births with CHD. Approximately two-thirds of TAPVR cases occur in isolation, with the remaining one third associated with complex CHD.
There are four types of TAPVR based on the anatomic site of the anomalous connection, with type I the most common (45-50% of cases):
- Type I, supracardiac
- Type II, cardiac
- Type III, infracardiac
- Type IV, mixed pattern
TAPVR may be present with or without obstruction to pulmonary venous return. TAPVR with obstruction implies no oxygenated blood is returning to the heart and is thus a surgical emergency. Isolated TAPVR is difficult to diagnose as at first glance, the four-chamber view will appear normal. However, there are certain sonographic clues that can help in diagnosis. These include the following:
- Absence of connection between pulmonary veins and left atrium with smooth left atrial wall
- Increased distance between the left atrium and descending aorta
- Twig sign”: Confluent vein (tubular vascular confluence) seen posterior to the left atrium and anterior to the descending aorta
- Bulging of the interatrial septum into the left atrium
- Enlarged right atrium/ventricle due to increased venous return to the right side of the heart
- Dilated coronary sinus with type II lesions
Figure 16: Total anomalous pulmonary venous return (TAPVR). Note the absence of any direct connection between the pulmonary veins and the posterior wall of the left atrium, thus giving the posterior wall a smooth appearance.
Figure 17: TAPVR. A direct vascular connection into the left atrium is not visualized. Rather, a confluent vein is noted which is a tubular venous confluence chamber. As it resembles a twig, it is often referred to as the “twig sign”.
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