Congenital heart defects (CHDs) are the most frequent congenital malformations, the costliest hospital admissions for structural defects and the leading cause of infant general and malformations related mortality. Fetal echocardiography represents a skilled ultrasound examination, because of the complexity, physiological and structural particularities of the fetal heart. The efficiency of the cardiac scan is reported with great variation, depending on the scanning protocol, examiner experience and equipment quality but CHDs remains among the most frequently missed congenital abnormalities.
- heart defects
1. Epidemiology. Incidence and risk factors for cardiac abnormalities
Congenital heart defects (CHD) are the most frequent congenital malformations (5–12 per 1000 live births), the costliest hospital admissions for structural defects and represent the leading cause of infant general and malformations related mortality (42%) [1, 2]. Prenatal CHD detection allows proper counseling, provides the options of pregnancy termination , in utero treatments (antiarrhythmics, valvuloplasties, etc.) [4, 5, 6, 7] and allows for delivery planning in a referral center [8, 9, 10, 11].
CHD etiology includes many genetic, environmental and teratogenic factors [12, 13, 14, 15, 16], but 90% of heart malformations have no identified cause. Conversely, the risk may be reduced with periconceptionally folic acid intake .
2. Indications and settings for fetal echocardiography (FECG)
A detailed sonographic examination, used to characterize fetal cardiac anatomy has traditionally been reserved for high-risk populations [18, 19, 20, 21, 22]: advanced maternal age, more than 35 years old, family history of CHD or disorders that involves potential CHD, infectious, autoimmune or metabolic diseases, exposure to drugs and teratogens. FECG was also proposed in certain pregnancy findings: structural defects, non-immune hydrops, arrhythmia, suspected chromosomal abnormalities, enlarged nuchal translucency, monochorionic multiple gestation. Nowadays, professional guidelines recommend a screening heart evaluation to all pregnancies, as most of the CHD cases are not associated with known risk factors [38, 39, 40, 41, 42, 43, 44, 45].
Guidelines and training requirements have been developed [18, 19]. An accurate visualization of heat features is commonly achieved at 18–22 gestational weeks. FECG is a relatively brief but skilled ultrasound examination, because of the complexity and prenatal physiological and structural particularities of the fetal heart. Consequently, FECG has not been widely implemented, and the prenatal diagnosis of even severe CHD varies considerably, with less than half prenatally detected.
3. Fetal heart evaluation. The cardiac sweep and longitudinal views
Optimal views of the fetal heart are obtained when the cardiac apex is orientated toward the anterior maternal wall. Heart anatomy is evaluated using a sequential segmental analysis, starting from the venous plane (atria with veins connections), following the blood flow to ventricles and great arteries . The information regarding fetal heart anatomy is achieved by examining five axial and three longitudinal scanning planes [18, 19, 24], described below, with examples of cardiac abnormalities. In general practice, only the axial sectional planes are evaluated during the cardiac sweep  (Figure 1).
Upper abdominal view facilitates the evaluation of normal abdominal situs by identifying the stomach, descending aorta and inferior vena cava position (Figure 1(1)).
Four-chamber view (4CV) is visualized in the lower half of the fetal chest, where the heart, with crux cordis occupying its central portion and a complete rib are present (Figure 1(2)). The evaluation parameters include:
Situs—the heart is normally left-sided, namely levocardia, or situs solitus. Rarely, a complete situs inversus is present. In the presence of an abnormal heart situs CHD but also congenital diaphragmatic hernia should be considered (Figure 2), as the presence of significant ectopic abdominal content in the chest displaces the heart.
Heart axis—normally, the apex points toward the left side at 45 ± 15–20° (Figure 1(2)). Some studies on CHDs suggested that an abnormal cardiac axis is present in more than two-thirds of the cases  (Figure 15C).
Area of the heart, is abnormally increased if higher than 1/3 of the thorax area, or cardio-thoracic circumference ratio is above two standard deviations  (Figure 3). It can arise from a number of situations which include CHD, particularly tricuspid atresia or dysplasia, including Ebstein’s anomaly, twin to twin transfusion syndrome, fetal dilated cardiomyopathies, hydrops fetalis, or may be due to abnormal shunting from arteriovenous malformations, as the vein of Galen malformation or placental chorioangioma (Figure 3).
The atria present similar size. The pulmonary veins enter the posterior left atrium and both vena cava enter the anterior right atrium (Figure 1(2)). Various condition may alter this spatial relation, as fetal isomerism and the normal atrial dimensions, where Ebstein’s anomaly is the most representative condition (Figure 4).
The ventricles should be visualized with similar width and contractility. The right ventricle is anterior, with more coarse lining and trabeculation. Abnormal shape of the ventricular wall lining may be an indicator for cardiac tumors, as tuberous sclerosis (Figure 5) or rhabdomyoma (Figure 6). Normally, the left ventricle forms the apex of the heart, the right ventricular apex contains the moderator band and septal insertion of the tricuspid valve is more apical than the mitral valve (Figure 1(2)). In later gestation, the right ventricle becomes slightly larger, but 2D or M-mode nomograms correlated with the gestational age or fetal biometry and Z-scores for fetal heart area and axis and cardiothoracic ratio, atrioventricular valve annuli, ventricular lengths and walls thickness, but also for emerging vessels, are available [29, 30]. A diminutive ventricle may be associated with significant CHD, as the hypoplastic left/right heart syndrome (Figure 7). Also, an abnormally small left ventricle may be an indirect sign of aortic coarctation (Figure 19A). However, less significant cardiac abnormalities may associate a larger right heart, as the persistence of left superior vena cava (Figure 8).
Ventricular septum integrity is better evaluated from a lateral incidence, with the ultrasound beam perpendicular to the septum. A dropout of echoes or an opening of the ventricular septum, causing communication between the two ventricles suggests the diagnosis. The entire septum must be swept (Figure 9) for a more confident diagnosis, and Doppler investigation enhances the diagnosis, especially for small defects (Figure 10). Ventricular septal defects are the most common cardiac abnormality and accounts for almost one third of all cardiac defects.
Atrial septum primum presence, at the crux of the heart, along the atrioventricular valves insertion which is more apical for tricuspid valve. Atrioventricular septal defects, known as endocardial cushion defects are situated in the central core of the heart. It involves the association of septum primum and ventricular septal defect and a variable degree of abnormal atrioventricular valves (Figure 11).
Foramen ovale represents about one third of the atrial septum and the flap bulges in the left atrium. A restrictive foramen ovale, because of a narrow foramen ovale orifice, or premature adhesion of the foramen ovale valve to the atrial septum, has repeatedly been discussed as a cause of fetal hemodynamic compromise . Foramen ovale aneurysm is defined as dilatation of the atrial septum with bulging of the septum at least half the distance to the left atrial wall (Figure 12), is primarily a defect of septum primum which results in: septum primum bulging, loss of the normal biphasic motion of foramen ovale and arrhythmia. Associated abnormalities include: atrial septal defect, tricuspid atresia, hypoplastic right heart, aortic stenosis, transposition of the great vessels, Ebstein anomaly, atrioventricular valve and pulmonary venous obstruction.
Pericardial effusion should be absent, or less than 2–4 mm. Greater effusions usually occur as a component of hydrops, as one of the earliest findings, and are also associated with cardiac structural abnormality, arrhythmia and an increased incidence of chromosomal anomalies (Figure 12) [32, 33].
Heart rate and the regularity of the rhythm is assessed based on the cardiac cycle length measured using M-mode or pulsed Doppler interrogation. Most common arrhythmias are transient and without clinical relevance, as brief episodes, less than 1–2 minutes of a bradycardic, tachycardic or irregular heart rhythm.
Irregular cardiac rhythm represents the most common rhythm anomaly and is almost always associated with isolated premature atrial contractions (PACs). Frequently blocked PACs will result in bradyarrhythmia that can mimic bradycardia (Figure 13). In rare cases, irregular rhythm may progress to supraventricular tachycardia.
Fetal bradycardia represents a persistently slower heart rate, of less than 100–120 beats/min. More concerning is the observation of sustained bradycardia induced by sinus bradycardia, atrial bigeminy and complete heart block. Heart block is frequently associated with maternal anti-Ro autoantibodies and CHD and the most common condition is an unbalanced atrioventricular septal defect associated with left isomerism.
Fetal tachycardia implies atrial and ventricular rates above 180 bpm. Fetal anemia, hypoxia, infections, and maternal thyrotoxicosis may induce this condition. The main causes of fetal tachycardia are supraventricular tachycardia (Figure 14), the most common cause, with atrioventricular re-entry due to a fast conducting accessory pathway), sinus tachycardia, and atrial flutter (with atrial rate 300–500 bpm and only every second or third atrial beat conducted across the atrioventricular node, resulting in ventricular rates of 150–250 bpm). The use of echocardiography is important to differentiate these conditions and their hemodynamic impact, because the severe conditions may lead to low cardiac output, hydrops and fetal demise.
Coronary sinus, may be demonstrated by fine sweeping caudally from the 4CV (Figure 8).
Given all these information, the 4CV is much more than a simple count of cardiac chambers, but certain abnormalities, especially involving great vessels, cannot be detected at the 4CV level alone . Recent revised and updated guidelines and recommendations from several professional bodies [18, 36, 37] plead for the routinely screening evaluation of the outflow tract views along the 4CV, based on strong medical evidence regarding the prenatal detection of CHD [38, 39, 40].
Left ventricular outflow tract (LVOT) is visualized cranially from the 4CV plane and directed toward the fetal right shoulder. In this five-chamber view, the ascending aorta appears arising from the left ventricle (Figure 1(3)), with no proximal transversal branching, allowing for its differentiation from the main pulmonary artery.
Septoaortic continuity, should be visualized as a continuous line between ventricular septum and aortic wall. The discontinuity of this structure is seen in the presence of a sub-aortic septal defect that is frequently associated with overriding. A good example of this condition is present in tetralogy of Fallot cases (Figure 15).
The aortic valve cusps should open freely, disappearing in systole and not thickened. Aortic dysplastic and stenotic valves do not fully open this will decrease the blood flow into the aorta. Aortic stenosis impairs the left ventricular development, leading to hypoplastic left heart syndrome (Figure 16).
The width of the aorta should be approximately equal with the pulmonary artery. Unbalanced blood flows through the outflow tracts as in Fallot Tetralogy, determine a larger aorta, because the aortic root receives blood from both ventricles due to overriding (Figure 15D and E). Valvular dysplasia and aortic arch stenosis/coarctation (Figure 16) determine a smaller aortic caliber.
Right ventricular outflow tract (RVOT) and short axis view are visualized cranially from the LVOT plane (Figure 1(4)), where the main pulmonary artery root arises from the anterior right ventricle with a short and straight course and soon branching into a large vessel, the ductus arteriosus directed straight posteriorly toward the descending aorta as an extension of the main artery, and the smaller pulmonary arteries directed laterally.
The pulmonary valve cusps should have a similar aspect as described for the aortic valves. The dysplastic stenotic valves may appear thickened and with incomplete opening during systole (doming) (Figure 17A) and determine pulmonary stenosis.
The approximately equal width of the two outflow tracts should be noted. Pulmonary stenosis may be associated with valvular stenosis, total anomalous pulmonary venous drainage, septal defects, supravalvular aortic stenosis, Noonan syndrome and tetralogy of Fallot. On color and pulsed Doppler investigation, pulmonary stenosis cases display turbulent or retrograde flow in and increased velocities distal to the valve (Figure 17Band C), with PSV higher than the aortic flow. A post-stenotic dilatation of the proximal pulmonary artery may be seen (Figure 17D). A variable degree of hypoplastic right ventricle with hypertrophic wall, dilatation of the right atrium, and tricuspid insufficiency may be present, while congestive heart failure and hydrops may occur in severe stenosis.
Spatial relationship evaluation should note crossing of aorta at a right angle and characteristic early transversal branching of the pulmonary artery (Figure 1(4)). In the absence of these ultrasound features, transposition of the great arteries should be suspected (Figure 18).
Three-vessel and trachea view (3VTV) is obtained sliding cranially in the upper thorax during cardiac sweep (Figure 1(5)). Superior vena cava (SVC) on the right side, the aortic arch and ductal arch, anterior and to the left of the aorta, are visualized. The approximately equal arterial arches form a “V”-shaped confluence toward the descending aorta, in the left of the spine. This plane is also used for thymus evaluation .
This view may be altered with regard to several features. Their width may be discrepant, as due to aortic coarctation, where the aortic isthmus is significantly smaller than the arterial duct (Figure 19). However, this diagnosis is challenging and affected by high rates of false-positive diagnoses. Thus, to improve detection, a multiple-criteria prediction model is adopted, as a combination of isthmic/duct and ventricular diameters ratios and Z-scores, visualization of CoA shelf and isthmic flow disturbance [42, 43].
Another abnormality of 3VTV plane is represented by the impossibility to identify all the three vessels. One of the arterial arches may not be seen, as in the presence of an interrupted aortic arch (Figure 20), or more than three vessels may be present, as in persistent left superior vena cava (Figure 21).
The superior vena cava may be identified contralateral, on the left side, as in the persistent of left superior vena cava (Figure 8).
Absence of a normal “V”-sign confluence of the arterial arches can be used to detect aortic arch abnormalities: right aortic arch, double aortic arch (Figure 22) and interrupted aortic arch (Figure 20).
Aortic and ductal arches views
The aortic and ductal arches are visualized in longitudinal planes aligned with the respective ventricular outflow tracts. Aorta origins from the middle of the heart, with a typical “hook” shape, with the neck vessels arising longitudinally (Figure 23A).
A diminutive caliber accompanied by an altered shape may be present in aortic arch coarctation (Figure 24A) or stenosis (Figure 16D). Also, the course of the arch may be misshaped and interrupted, with lack of communication with the descending aorta, as in interrupted aortic arch (Figure 24C).
The vessel may appear irregular and thin, as in pulmonary stenosis (Figure 24B), or heavily dilated, as in aortic arch stenosis or interruption (Figure 24D). The ductus may be absent, as is usually in the most frequent variant of absent pulmonary valve syndrome-associated with tetralogy of Fallot. Another type of the syndrome—accompanied by tricuspid atresia, is characterized by a normal or narrowed ductus arteriosus, along the dysplastic right ventricle. Contrarily, the isolated type of absent pulmonary valve syndrome, with intact ventricular septum, associates a severe right ventricular hypertrophy with pulmonary artery and ductus arteriosus dilatation.
Superior and inferior vena cava views/caval long-axis view/bicaval view is found longitudinally on the right of the spine, in line with the superior and inferior vena cava confluence with the right atrium (Figure 23C). The normal aspect is altered in fetal isomerism, interrupted inferior vena cava or persistent left superior vena cava.
4. Doppler imaging
Color Doppler and high definition directional power flow sonography allows for a better understanding of the cardio-vascular anatomy and function [18, 45, 46], particularly in detecting regurgitation, small septal defects and first trimester anatomic and physiological features of heart, as presented below. The ductus venosus appearance, flow and connections depend on the Doppler identification and interrogation of this small vascular structure. Agenesis of ductus venosus was associated with a high incidence of cardio-vascular and genetic abnormalities (Figures 25 and 26).
Pulsed Doppler sonography is an adjunct to evaluate the cardiac rhythm, but also the blood flows at the level of various arteria or venous vascular sites and valves.
B-flow and classic power Doppler display in some cases greater sensitivity in imaging cardio-vascular blood flow, but they are not routinely used.
5. 4D spatiotemporal image correlation (STIC)
Volume datasets obtained with 4D STIC ultrasonography allow the evaluation of virtual planes not available for direct visualization with 2D technique, and facilitates the reconstruction of the spatial relationships between the cardio-vascular structures (Figure 27). This technology has the potential to increase the CHD detection rate by decreasing the dependency on sonographer skills and experience. However, due to the expensive costs and lack of specialists for training and interpretations, the technique is not routinely used.
In selected cases, it may offer important information as the comprehensive assessment of complex CHD cases [47, 48, 49, 50] and the evaluation of cardiac function and quantification of fetal hemodynamic parameters, such as cardiac output .
6. Cardiac function
It should be considered for suspected structural or functional cardiac anomalies [18, 19]. Some qualitative markers are identified during standard scanning: cardiomegaly, atrioventricular valve regurgitation, and hydrops. The quantitative assessment of heart function includes the study of myocardial movement such as tissue Doppler, myocardial/ventricular strain, strain rate imaging, fractional shortening and the myocardial performance index [52, 53, 54].
7. Efficiency of the fetal cardiac scan
Although the most frequent congenital malformations, CHDs are among the most frequently missed [18, 55]. The efficiency of the cardiac scan is reported with great variation, depending on the scanning protocol, examiner experience, equipment quality and scanning conditions [18, 56, 57, 58]. It appears that the use of 4CV alone detects up to 77% of CHD, while adding OTV increases prenatal detection to 83–92% of major abnormalities.
8. Early evaluation of the fetal heart, at the first trimester (FT) morphogenetic scan
Congenital heart defects appear during the first 8 weeks of the fetus development, thus cardiac sonography at the genetic scan, during 11–13 gestational weeks (GW) is feasible (Figure 28) and identifies numerous abnormalities (Figures 29–35) [59, 60, 61]. The rate of complete cardiac evaluation increases with gestational age, from 20% at 11GW, to more than 92% at 13–15 GW, especially when transvaginal route was used [62, 63].
Regarding the imaging technique, gray scale is the basis of a reliable fetal cardiac scan in the ST, but much less informative in the FT .
For safety reasons, routine use of pulsed color Doppler is advised against in the FT , although tricuspid and ductus venosus flows are commonly used [66, 67, 68, 69, 70, 71, 72] and color Doppler improves early visualization of cardio-vascular features, due to the low discrimination of the heart structures in gray-scale mode [73, 74, 75], while respecting the ALARA principle (As Low As Reasonably Achievable) .
At a lesser extent, the FT examination protocol is similar to the second trimester cardiac scan [77, 78], as presented in Figure 28. 4D-STIC is feasible in the FT and likely to improve CHD detection in expert hands.
The efficiency of FT cardiac scan varies widely (detection rate 5.6–90%), depending on the protocol used, population risk and scanning route (TV, TA or both). High detection rates for major CHD were reported even in unselected or low risk population 80–90%, when using an extended standardized protocol [74, 75]. A systematic review of the literature  reported a pooled sensitivity and specificity of 85% (95% CI, 78–90%) and 99% (95% CI, 98–100%), respectively. Thus, FT cardiac scan has a high accuracy in major CHD detection and a reasonable accuracy to diagnose normal heart. We should underline during parents counseling that normal fetal cardiac features examinations at any time of pregnancy do not exclude CHD, as some diseases evolve in utero and become apparent later during pregnancy: coarctation of aorta, pulmonary stenosis, tetralogy of Fallot, hypoplastic left heart syndrome, cardiomyopathy or cardiac tumors [80, 81, 82, 83]. Ventricular septal defects are the earliest missed lesions because of the small size of the lesion and low flow velocities in the FT. A normal cardiac scan in the FT should not be considered a replacement for the second trimester echocardiography.
Markers for cardiac abnormalities (Figure 36) may also be useful in early pregnancy, as increased nuchal translucency (NT) and abnormal ductus venosus and tricuspid flows. Increased NT was associated with cardiac dysfunction and abnormalities, even in chromosomally normal fetuses, but not obviously related to any particular type of cardiac anomaly [84, 85, 86]. The prevalence of CHD when NT is the 95th percentile is up to 20%  and about six times higher than unselected population for NT ≥99th percentile . Still, NT measurement is not a reliable screening test for CHD during FT, because of the overall low detection rates for CHD (around 15%) in unselected or low-risk populations [89, 90].
The performance of early screening for CHD achieved by measurement of fetal NT is improved by the assessment of ductus venosus and tricuspid valve flow pattern. In fetuses with enlarged NT (above 95 centile) and absent or reversed a-wave in DV flow the risk for major CHD is tripled . The finding of reversed a-wave in chromosomally normal fetuses increases by almost 10 times the risk of CHD, with a predominance of right-heart anomalies regardless of the measurement of NT . Also, chromosomally normal fetuses with tricuspid valve regurgitation have an 8-fold increased risk for CHD [92, 93].