Assessment of Coronary Arteries during the Prenatal and Postnatal Periods using Two- and Three-dimensional Ultrasound

Abstract

Coronary artery (CA) development is a complex process that begins early in embryogenesis and continues throughout fetal and postnatal life, with important implications for cardiovascular health. This review summarizes current knowledge on CA embryology, physiology, and imaging assessment across the fetal–neonatal continuum, with particular emphasis on advances in prenatal and postnatal ultrasonography. Prenatal evaluation using two-dimensional (2D) ultrasonography and three-dimensional techniques, including spatiotemporal image correlation and advanced flow-rendering modalities, has expanded the ability to visualize CA anatomy in selected fetal conditions, particularly in the presence of abnormal coronary dilation or altered hemodynamics, although routine assessment of normal fetal CAs remains challenging. In the postnatal period, 2D transthoracic echocardiography remains the cornerstone for the diagnosis and follow-up of CA anomalies, aneurysms, and fistulas, supported by standardized measurement protocols and Z-score normalization. Complementary imaging modalities, such as computed tomography and magnetic resonance coronary angiography, provide additional anatomical detail in selected cases. A comprehensive understanding of CA development and imaging across early life is essential for improving diagnostic accuracy, guiding clinical management, and optimizing long-term cardiovascular outcomes.

INTRODUCTION

In 2023, the International Society of Ultrasound in Obstetrics and Gynecology updated its guidelines for fetal cardiac screening with the aim of maximizing the detection of structural, functional, and rhythm abnormalities as part of routine prenatal care.[1]

The prenatal diagnosis of congenital heart disease (CHD) has been recognized for several decades as a major contributor to improved neonatal survival and prognosis, as it enables specialized prenatal follow-up and postnatal planning in referral centers. Certain types of CHD without prenatal diagnosis may expose the neonate to hemodynamic decompensation within hours after birth, constituting a medical emergency. Delayed diagnosis may result in irreversible sequelae and lead to death.

The cardiovascular system is the first organ system to reach a functional state. Embryonic cardiac activity can be detected by Doppler ultrasonography during the 4^th week of gestation, approximately 6 weeks after the last normal menstrual period.[2] Human cardiocirculatory ontogenesis recapitulates, over a 5-week period, a phylogenetic evolution spanning 400 million years. This process is characterized by profound anatomical and functional changes that culminate in the complexity of the human heart.[3] During the transition from intrauterine to extrauterine life, the heart relies on well-orchestrated and complex biochemical, physiological, and anatomical changes occurring in a timely manner to ensure neonatal survival.[4] From an endocardial tube, through processes of looping, fusion, septation, and the formation of arterial and venous trunks, a four-chambered heart is formed, which during fetal life functions to ensure efficient distribution of more oxygenated blood to vital organs.[3]

To function adequately, the human heart requires a specific blood supply provided by the coronary arteries (CAs), which originate from the aortic sinuses and their branches.[5] Recognition of normal coronary anatomy, anatomical variants, and CA anomalies is essential in the management of both congenital and acquired heart diseases in the pediatric population. CA anomalies are a well-recognized feature of many forms of CHD, particularly those involving the conotruncal region, such as transposition of the great arteries, tetralogy of Fallot, truncus arteriosus, and congenitally corrected transposition of the great arteries.[6] Transposition of the great arteries may result in anomalous origins and diverse CA courses. Similarly, the altered spatial relationship between the aortic and pulmonary valve levels determines that the origin, course, and distribution of the CAs differ from those observed in the anatomically normal heart.[7]

Prenatal diagnosis of CHD is a key element in improving the prognosis of structural CHD and optimizing the prevention of cardiovascular disease in hearts subjected to intrauterine insult. The development of two-dimensional (2D) ultrasound screening programs has improved the early detection of CHD. Detection rates were further enhanced by the addition of ventricular outflow tract and upper mediastinal views to the classic four-chamber view during fetal cardiac assessment.[8]

Advances in imaging technologies have increased prenatal detection of CHD, with a positive impact on reducing CHD-related perinatal mortality. Three-dimensional (3D) ultrasonography, developed in the early 1990s, and particularly the Spatiotemporal Image Correlation (STIC) software introduced in the early 2000s, enabled major technological advances in 3D fetal cardiac assessment. Acquired 3D volumes contain a “block” of cardiac ultrasound images that allow detailed analysis of cardiac anatomy. In addition, this approach offers the advantage of reduced operator dependency and shorter examination times, as volume analysis can be performed offline, in the absence of the pregnant woman.[8]

There are no studies defining technical criteria for measuring CA diameter in the fetal heart. The literature describes that, although rare, coronary hypoplasia is usually associated with other cardiac anomalies, such as pulmonary atresia. Another reported example is enlargement of the left CA diameter as a consequence of left ventricular hypertrophy, which may represent an adaptive mechanism to maintain adequate coronary blood flow.[7]

The stimulus for increased CA cross-sectional area is not fully understood; however, several mechanisms are considered possible, including coronary blood flow, myocardial hypertrophy, and microvascular alterations. Vasoactive substances, such as endothelium-derived relaxing factor, increase proportionally with coronary flow and may therefore stimulate CA growth. Humoral factors (growth factors) or mechanical stimuli responsible for myocardial hypertrophy may also lead to increased CA size, in addition to coronary vasomotor tone, another important factor influencing CA dimensions.[7] The STIC rendering method has been applied to the assessment of various fetal cardiac structures, such as interventricular septal areas, atrioventricular valves, papillary muscles, and myocardium.[8,9,10,11] This technique, combined with newer software such as HDlive Silhouette and HDlive Flow, enables realistic images and clear delineation of cardiac structural borders, which is particularly important for identifying small structures such as the CAs.[12,13]

In the postnatal period, measurement of CA diameter is of great importance in cases of Kawasaki disease. This condition is characterized by an acute vasculitis of unknown etiology that causes focal vascular destruction of the CAs, with subsequent development of aneurysms, with an incidence of 15%–25% in untreated infants and children.[14,15] Kawasaki disease is the leading cause of acquired heart disease in children in developed countries[16] and is associated with multiple morbidities, including hepatic involvement, which may progress to severe cholestatic hepatitis or gallbladder hydrops.[17] In 1984, the Ministry of Health and Welfare of Japan (Research Committee on Kawasaki Disease) defined criteria for CA abnormalities in Kawasaki disease. According to these criteria, CAs are classified as abnormal if the internal luminal diameter is >3 mm in children younger than 5 years or >4 mm in children older than 5 years.[18] However, CA diameter measurements should be normalized to body surface area,[19] which is commonly performed using Z-score calculations. Several studies in different populations have been published describing reference curves for CA diameter Z-scores in children using 2D echocardiography.[15,20,21,22]

The aim of this study is to review the main concepts related to the embryology, physiology, prenatal 2D and 3D ultrasonographic assessment, and postnatal echocardiographic evaluation of the CAs.

EMBRYOLOGY

The formation of the human heart involves complex biological signaling pathways, interactions among myocardial progenitor cells, and the development of the cardiac tube. To facilitate survival in the hypoxemic intrauterine environment, the fetus exhibits structural, physiological, and functional cardiovascular adaptations that are fundamentally different from those of the neonate.[4]

The cardiovascular system is the first system to become functional in the embryo. The primitive heart and vascular system appear during the middle of the 3^rd week of development. This early cardiac development occurs to meet the growing need for an efficient method of acquiring oxygen and nutrients from the maternal blood and eliminating carbon dioxide and metabolic waste products. Around day 18, the lateral plate mesoderm differentiates into somatopleure and splanchnopleure; the latter gives rise to nearly all components of the heart. These initial endocardial cells separate from the mesoderm to form paired cardiac tubes. As lateral embryonic folding occurs, the paired endocardial heart tubes approach each other and fuse to form a single cardiac tube.[2]

The endothelial tube becomes the inner endothelial lining of the heart, known as the endocardium, while the primitive myocardium forms the muscular wall of the heart, or myocardium. Simultaneously, the tubular heart elongates and develops alternating dilations and constrictions: the cardiac bulb (composed of the truncus arteriosus, conus arteriosus, and bulbus cordis), ventricle, atrium, and sinus venosus. Embryonic blood vessels also begin to develop, as the initial formation of the cardiovascular system is directly related to the increasing need for blood vessels to deliver oxygen and nutrients to the embryo from the maternal circulation via the placenta. The formation of the embryonic vascular system involves two processes: vasculogenesis and angiogenesis. Vasculogenesis refers to the formation of new vascular channels through the coalescence of individual cellular precursors (angioblasts), whereas angiogenesis refers to the formation of new vessels by sprouting and branching from preexisting vessels.[2]

The heart and great vessels develop from mesenchymal cells in the cardiogenic area. Longitudinal, paired endothelial channels, also known as endocardial tubes, fuse to form the primitive cardiac tube. The tubular heart connects to the embryonic blood vessels, the connecting stalk, and the umbilical vesicle, forming the primitive cardiovascular system. Cardiac contractions begin around day 21 or 22 of development.[2]

The vitelline veins accompany the omphalomesenteric duct into the embryo. This duct is a narrow tube that connects the yolk sac to the midgut. After passing through the septum transversum, which provides a pathway for blood vessels, the vitelline veins enter the venous end of the heart, the sinus venosus. The left vitelline vein regresses, whereas the right vitelline vein forms most of the hepatic portal system as well as a portion of the inferior vena cava. The cardinal veins constitute the main venous drainage pathways of the embryo. The anterior and posterior cardinal veins drain the cranial and caudal portions of the embryo, respectively. They unite to form the common cardinal veins, which enter the sinus venosus.[2]

The initial cardiac contractions are myogenic in origin, arising within the muscle itself. The muscular layers of the atrial and ventricular inflow and outflow tracts are continuous, and contractions occur as peristaltic waves beginning in the sinus venosus. Initially, circulation through the primitive heart consists of a to-and-fro flow pattern; however, by the end of the 4^th week, coordinated cardiac contractions result in unidirectional blood flow. The sinus venosus initially opens into the center of the dorsal wall of the primitive atrium, with its right and left horns being nearly equal in size. Progressive enlargement of the right horn occurs due to two left-to-right blood shunts: the first resulting from transformations of the vitelline and umbilical veins, and the second from the formation of an anastomosis between the anterior cardinal veins. By the end of the 4^th week, the right horn of the sinus venosus is clearly larger than the left. As the right horn enlarges, it receives all the blood from the head and neck via the superior vena cava and from the placenta and caudal regions of the body via the inferior vena cava. Initially a separate chamber, the sinus venosus opens into the dorsal wall of the right atrium. The left horn becomes the coronary sinus (CS), whereas the right horn is incorporated into the wall of the right atrium.[2]

After completion of the internal septation of the heart during the embryonic period, the coronary circulation is established, developing from two primordial sources. The proximal primordium, consisting of preepicardial progenitor cells, is involved in the formation of vessels arising from the sinuses of Valsalva (typically the aorta and, more rarely, the pulmonary trunk). The distal primordium consists of a developing vascular network within the mesodermal angioblasts of the developing myocardium.[23,24]

The aortic root forms the initial portion of the ascending aorta and is composed of three relatively similar semilunar valve leaflets, three interleaflet triangles, and the three sinuses of Valsalva. The sinotubular junction, a circumferentially thickened region of the aortic wall at the transition between the sinuses and the tubular aorta, separates the aortic root from the ascending aorta. Of the three sinuses of Valsalva, two are adjacent to the pulmonary root, and the main CAs usually originate from these sinuses. CA origins above the sinotubular junction, from the nonadjacent CS, or near the peripheral insertions of the zones of apposition between the valve leaflets are considered anatomical variants.[25,26]

Before coronary development, the heart consists of a thin myocardial muscle layer that is easily oxygenated by the blood flowing through its lumen and therefore does not initially require its own vascular bed. As the heart increases in size, coronary blood vessels subsequently begin to emerge in the ventricles as an immature vascular plexus.[27]

Although it is well established that CHD alters the hemodynamic transition to the extrauterine environment, other common pregnancy complications, including fetal growth restriction (FGR), prematurity, and preeclampsia, have also been shown to adversely affect cardiac remodeling in the offspring before, during, and after the transitional period. Any irregularity in the spatial arrangement of the great vessels or ventricles leads to defects in angioblast fusion within the coronary vessels and in the projections arising from the sinuses of Valsalva. CA anomalies affect both their origin and distribution, and their identification is crucial for preoperative assessment and surgical management of patients.[4,23]

ASSESSMENT OF CORONARY ARTERIES IN THE PRENATAL PERIOD BY TWO-DIMENSIONAL ULTRASONOGRAPHY

The CAs play a crucial role in meeting the metabolic demands of the heart. Identifying abnormalities in early cardiogenesis and in the transitional cardiovascular physiology from fetal to neonatal life is essential for assessing both immediate and long-term cardiovascular risk in neonates.[4]

During the early stages of human fetal development, vascular sinusoids develop within the embryonic myocardium. As the myocardium becomes compacted, these sinusoids disappear, giving rise to a network of veins, arteries, and capillaries that communicate with other mediastinal vessels at approximately 32 days of gestation. Primitive coronary vessels appear around the 7^th week of gestation, following the formation of the aorta after division of the truncus arteriosus. As the coronary arterial network develops, endothelial buds arise at the base of the truncus arteriosus and subsequently connect with the coronary arterial network derived from the sinusoids, thereby establishing the definitive coronary arterial system. Abnormal involution, altered positioning of the endothelial buds, or abnormal septation of the truncus arteriosus may lead to anomalies in the origin of the CAs.[28]

This process of embryonic arteriogenesis, therefore, requires the orchestration of multiple events, including migration of smooth muscle cells and pericytes from the epicardium and the aortic root, assembly of these cells with the developing vascular structures, and radial growth and regression of these vessels. Apoptosis is a necessary regulator of vessel formation at this stage. Initially, however, primitive vascular structures remain functionally ambiguous, with their arterial or venous identity becoming apparent only after anastomosis with the aortic valvar sinuses or tributaries of the systemic venous sinus. Before establishing contact with the aorta, orifices in the aortic wall and invading capillaries are generated by apoptosis. Although the basic morphological changes in coronary system development have been well studied, the underlying molecular mechanisms remain largely unknown. Nevertheless, it is recognized that defects at any stage of this highly complex process may result in the development of CA anomalies.[25,28]

There is also accumulating circumstantial evidence indicating that coronary entry into the aortic valvar sinuses is governed by the initial septation process of the arterial roots, such that the main CAs preferentially originate from the aortic valvar sinuses adjacent to the developing pulmonary root. Further evidence suggests that the developing pulmonary infundibular myocardium is impermeable to the passage of developing CAs. These two processes are closely involved in the potential generation of significant variations in the arrangement and course of the CAs.[25,28]

Coronary–aortic connections, referred to as ostia or trunks, are normally observed in the left and right aortic valvar sinuses closest to the pulmonary artery and not in the non-CS, which is located 180° opposite the aorta–pulmonary artery interface. Congenital CAs arise when aortic alignment is abnormal, ranging from incorrect positioning of the CA within the aorta to defective connections with the pulmonary artery.[27]

Typically, the left CA (LCA) originates from the left CS and courses leftward and posteriorly. Near the pulmonary trunk, it bifurcates into two branches: the left anterior descending artery (LAD), located in the anterior interventricular sulcus and responsible for supplying the anterior two-thirds of the basal septum as well as the mid and apical septal regions, and the circumflex artery, which runs within the left atrioventricular sulcus and supplies the left ventricular wall. In contrast, the right CA (RCA), which originates from the right CS, supplies the right ventricular wall and follows an anterior and rightward course between the right atrium and the pulmonary artery, within the atrioventricular sulcus.[26,28]

Congenital CA anomalies may occur as isolated lesions, with an incidence ranging from 0.21% to 5.79% depending on the diagnostic method used (angiography, computed tomography, or autopsy), or more commonly in association with CHD, particularly conotruncal malformations, in which CA anomalies represent a negative prognostic factor. The anatomical classification of CA anomalies comprises four categories: (1) Anomalies of origin and course; (2) anomalies of intrinsic CA anatomy; (3) anomalies of CA termination; and (4) anomalous anastomotic vessels.[25,28,29]

The CS is located adjacent to and slightly posterior to the mitral valve annulus, within the left atrioventricular sulcus. The CS drains into the right atrium below the level of the foramen ovale and just above the inferior vena cava valve, and it represents the main route of coronary venous return. In some cases, the CS becomes dilated due to volume overload or, more rarely, pressure overload.[30]

During intrauterine life, fetal intracardiac circulation within the CAs can be assessed using color and spectral Doppler. Coronary blood flow recordings can be obtained in normal fetuses late in gestation, whereas assessment at earlier gestational ages is feasible in the presence of coronary vasodilation, which is closely associated with severe intrauterine hypoxia.[31,32,33]

Chaoui[34] described a technique for prenatal visualization of the CAs that consists of obtaining a transverse section of the aortic valve in the apical short-axis view, followed by upward and clockwise movement of the transducer until the LCA is visualized. The RCA can be demonstrated by moving the transducer from the same plane upward and counterclockwise until the tricuspid valve leaflets disappear [Figures 1 and 2]. Figure 3 illustrates measurements of the diameters of the RCA and LCA in a fetus with transposition of the great arteries.

Figure 1.

Axial view of the right ventricular outflow tract in a normal 28-week fetus, demonstrating the right coronary artery above the aortic valve annulus (red arrows) (a) and the corresponding internal diameter measurement (b). RCA: Right coronary artery

Figure 2.

Axial view of the right ventricular outflow tract in a normal 28-week fetus, demonstrating the left coronary artery below the aortic valve annulus (red arrows) (a) and the corresponding internal diameter measurement (b). LCA: Left coronary artery

Figure 3.

Axial view of the right ventricular outflow tract in a 31-week fetus with transposition of the great arteries, demonstrating the right coronary artery above the aortic valve annulus (red arrows) (a) and the corresponding internal diameter measurement (b). RV: Right ventricle; RCA: Right coronary artery; AO: Aorta

ASSESSMENT OF CORONARY ARTERIES IN THE PRENATAL PERIOD BY THREE-DIMENSIONAL ULTRASONOGRAPHY

The STIC software allows assessment of the fetal heart and its vessels using multiplanar and rendering modes. The cineloop function enables evaluation of fetal cardiac motion memory, simulating a complete cardiac cycle.[35] STIC allows the creation of virtual planes that cannot be obtained with 2D ultrasonography and improves visualization of the interatrial septum, interventricular septum, foramen ovale, and atrioventricular valves.[36,37] In addition, several fetal cardiac structures, including the interventricular septum, atrioventricular valves, and ventricular papillary muscles, can be more accurately delineated by adjusting brightness and color compared with conventional 2D ultrasonography.[38,39]

In the normal heart, the two main CAs originate from the right and left aortic sinuses of Valsalva, which are oriented toward the subpulmonary infundibulum. When visualized in the frontal plane, the RCA originates at an angle close to 90° relative to the aortic wall, whereas the LCA usually descends at approximately 45°, although this angle may range from 25° to 90°. In most, but not all, cases, LAD arises from the LCA together with the circumflex artery. The posterior descending artery and the infundibular artery are branches of the RCA.[29]

In fetuses, CAs may be visualized when dilated, such as in cases of FGR or coronary fistulas. However, visualization of normal CAs is considerably more challenging and has not yet been reported systematically. Recently, during standard fetal echocardiographic examinations using a high-frequency convex transducer (2–9 MHz) combined with a new generation of high-definition color Doppler (“bright” Doppler; Radiantflow^®; General Electric Healthcare, Zipf, Austria), it was incidentally observed that, in several cases, the origin of the CAs from the sinuses of Valsalva was visible.[29]

HDlive Flow combined with STIC technology may enhance prenatal diagnosis of small fetal arterial and venous anomalies, as it provides high-resolution blood flow images, which are particularly valuable for detecting subtle vascular abnormalities within the small and intricate fetal circulatory system. Conventional 2D ultrasound often struggles to identify small or concealed vascular irregularities, whereas HDlive Flow enables clearer visualization of blood vessels, allowing clinicians to detect conditions such as arterial stenosis, venous dilatation, or malformed vessels that might otherwise go unnoticed.[40] Li et al.[41] described a case of prenatal diagnosis of a coronary fistula in a 25-week fetus using STIC with HD flow. On 2D ultrasonography, an abnormal tubular structure was observed outside the right atrioventricular groove, and color Doppler demonstrated blood flow filling this tubular structure, with flow directed into the right ventricle on the four-chamber view. STIC rendering mode and HD flow were used to demonstrate the RCA and clearly depict the fistula between the RCA and the right ventricle.

We have developed a technique for measuring CA diameters using 3D ultrasonography with STIC and HDlive Silhouette mode. For cardiac volume acquisition, the four-chamber plane is used as a reference whenever possible, ideally with the fetal spine positioned as close as possible to the 6 o’clock position and the ultrasound beam perpendicular to the interventricular septum. The entire fetal heart, including its vascular connections, is included within the smallest possible region of interest (ROI), according to the standardized technique described by Gonçalves et al.[42] Using the 4D View software (General Electric Healthcare, Zipf, Austria), the fetal heart image is displayed in multiplanar mode: axial or transverse (A), corresponding to the acquisition plane; sagittal or longitudinal (B); and coronal or frontal (C).

To obtain the right and left ventricular outflow tracts, we used the technique standardized by Gonçalves et al.[35] The axial plane (acquisition plane-A) is selected as the reference, and the reference point is moved to the cardiac crux. The heart is rotated around the “z” axis so that the apex is positioned at 12 o’clock. Subsequently, the heart is rotated again around the “z” axis to position the axis at 10 o’clock, at which point the reference point is moved to the midpoint of the interventricular septum. The A plane is then slightly rotated around the “y” axis to open the left ventricular outflow tract. The reference point is moved to below the aortic valve, automatically generating the right ventricular outflow tract in the sagittal plane (B).

The A plane is then slightly displaced along the “z” axis to position the left ventricular outflow tract horizontally, with the reference point at the level of the aortic valve annulus. Render mode and the ROI selection tool are activated, with the ROI direction (green line) oriented from right to left and positioned in plane B at the level of the aortic valve annulus, allowing visualization of the RCA above the aortic valve. At this point, Render Mode is reactivated using HDlive Surface and Gray Silhouette. Using the cineloop function, the plane of maximal aortic valve opening during ventricular diastole is obtained. The RCA diameter is measured above the aortic valve as the distance between two points [Figure 4].

Figure 4.

Left ventricular outflow tract plane in spatiotemporal image correlation mode with HDlive Silhouette, demonstrating the right coronary artery above the aortic valve annulus (red arrows) (a) and the corresponding internal diameter measurement (0.08 cm) (b). LV: left ventricle; RCA: Right coronary artery; AOv: Aortic valve

To obtain the LCA, plane A is selected as the reference and rotated around the “y” axis in 180°, transforming it into the right ventricular outflow tract. The ROI selection tool is activated with the ROI direction oriented from right to left in plane B, positioning the green line at the level of the upper border of the aortic valve, and the reference point placed at the center of the LCA in plane A. Render Mode is then reactivated with HDlive Surface and Gray Silhouette. Using the cineloop function, the plane of maximal aortic valve opening during ventricular diastole is obtained. The LCA diameter is measured above the aortic valve [Figure 5]. Figure 6 shows the measurement of the RCA diameter in a fetus with hypoplastic left heart syndrome.

Figure 5.

Short axis right ventricular outflow tract plane in spatiotemporal image correlation mode with HDlive Silhouette, demonstrating the left coronary artery above the aortic valve annulus (red arrows) (a) and the corresponding internal diameter measurement (b). RV: Right ventricle; RVOT: Right ventricule outflow tract; PA: pulmonary artery; LCA: Left coronary artery; AOv: Aortic valve

Figure 6.

Left ventricular outflow tract plane in spatiotemporal image correlation mode with HDlive Silhouette, demonstrating the right coronary artery above the aortic valve annulus (red arrows) (a) and the corresponding internal diameter measurement (0.15 cm) (b) in a 23-week fetus with hypoplastic left heart syndrome. RV: Right ventricle; LV: Left ventricle; RCA: Right coronary artery; AO: Aorta

ASSESSMENT OF CORONARY ARTERIES IN THE POSTNATAL PERIOD BY TWO-DIMENSIONAL ULTRASONOGRAPHY

Anomalous origin of coronary arteries: Postnatal features

Anomalous origins of the CAs may present with a broad spectrum of postnatal clinical manifestations, ranging from incidental, asymptomatic findings to severe complications such as myocardial ischemia, heart failure, or sudden cardiac death. Prognosis and clinical presentation largely depend on the specific coronary anomaly, the degree of impairment of myocardial perfusion, and the extent of collateral circulation. Timely identification and accurate diagnosis are essential to guide optimal management strategies and improve patient outcomes.

Postnatal echocardiographic assessment of the CAs requires high-frequency transducers (>8 MHz) and specific imaging settings optimized for small-caliber vessels. Parasternal long- and short-axis views are particularly useful for this evaluation. Color Doppler imaging and reduced compression are mandatory. For measurement of the left main CA, the LAD, and the proximal RCA, the calipers should be positioned distally, at a distance of 3–5 mm from the coronary origin, at the onset of systole. All CA dimensions should be measured from inner edge to inner edge[21,43] [Figure 7].

Figure 7.

Schematic illustration (a) and postnatal echocardiographic (b) showing measurement techniques (yellow lines) for the left main coronary artery, left anterior descending artery, and proximal right coronary artery in children. LCA: Left coronary artery; RCA: Right coronary artery; LAD: Left anterior descending artery; Cx: Circumflex coronary artery; Ao: Aorta; PA: Pulmonary artery. Anomalous left coronary artery from the pulmonary artery (ALCAPA), also known

Anomalous LCA from the pulmonary artery (ALCAPA), also known as Bland–White–Garland syndrome, is a rare CHD accounting for approximately 0.25%–0.5% of all CHD cases.[44,45] It represents one of the most common causes of myocardial ischemia in childhood and, if left untreated, is frequently fatal within the 1^st year of life. Myocardial ischemia in infants may present with symptoms resembling colic, such as episodic pallor and irritability. ALCAPA should be suspected when these manifestations are associated with heart failure, electrocardiographic abnormalities, and cardiomegaly.

In severe cases, progression may lead to dilated cardiomyopathy, heart failure, and/or mitral regurgitation. The clinical course depends largely on the extent of collateral coronary circulation, which is a critical determinant of survival into adulthood.[46] The preferred surgical approach for restoration of a dual coronary system is direct aortic reimplantation of the anomalous CA. Once the diagnosis of ALCAPA is confirmed, surgical intervention should be performed promptly. In pediatric patients, transthoracic echocardiography (TTE) is considered the primary noninvasive diagnostic modality.[47]

Real-time 3D echocardiography represents an adjunctive tool that may enhance conventional TTE imaging. Echocardiographic diagnostic criteria for ALCAPA include dilation of the RCA, retrograde color Doppler flow from the LCA into the pulmonary artery, and prominent septal collateral flow. Definitive diagnosis requires direct visualization of the origin of the LCA from the pulmonary trunk.[46] Additional noninvasive imaging modalities include computed tomography or magnetic resonance coronary angiography, both of which provide excellent accuracy in assessing anomalous coronary origins[47] [Figure 8].

Figure 8.

Coronary computed tomography angiography in a case of anomalous left coronary artery from the pulmonary artery. Note the left main coronary artery arising from the pulmonary artery. LCA: Left coronary artery; DA: Left anterior descending artery; RCA: Right coronary artery; Cx: Circumflex coronary artery

Coronary arterial aneurysm

A CA aneurysm (CAA) is defined as a localized dilatation of a CA segment measuring at least 1.5 times the diameter of the adjacent normal segment and involving <50% of the vessel length.[48] Factors contributing to the development of CAAs include Kawasaki disease (the most common cause in children), other vasculitides (e.g. polyarteritis nodosa, Takayasu arteritis), postsurgical conditions (balloon angioplasty, CA bypass grafting, or coronary reimplantation), connective tissue disorders (Marfan syndrome, Loeys–Dietz syndrome, and Ehlers–Danlos syndrome type IV), trauma, infectious etiologies (mycotic aneurysms), and rare congenital aneurysms. In adults, atherosclerosis is the most frequent cause.

Kawasaki disease is the leading cause of CA vasculitis in children, and if untreated, CAAs develop in approximately 20%–30% of affected patients.[49,50] During the severe acute respiratory syndrome coronavirus-2 pandemic, a subset of children developed a clinical syndrome resembling Kawasaki disease, occurring 2–4 weeks after peaks of acute Coronavirus disease 2019 cases. This condition was termed multisystem inflammatory syndrome in children (MIS-C) with a Kawasaki-like phenotype. MIS-C is characterized by systemic inflammation with manifestations such as circulatory shock, myocardial dysfunction, and pericarditis. Notably, the age distribution differs between the two conditions: Kawasaki disease typically affects children aged 0–5 years, whereas MIS-C presents at a mean age of approximately 8 years.[51]

In children, CAAs are classified according to Z-scores (standard deviations from the mean normalized for body surface area) and absolute dimensions as follows: small (Z ≥ 2.5 to < 5), medium/large (Z ≥ 5 to < 10 or absolute diameter 5–8 mm), and giant (Z ≥ 10 or ≥ 8 mm).[21,43] This classification guides long-term monitoring and therapeutic strategies, as larger and persistent aneurysms require closer surveillance due to increased risks of thrombosis and myocardial ischemia. Based on morphology, aneurysms are further classified as saccular (spherical or sac-like outpouching) or fusiform (elongated, spindle-shaped dilatation) [Figure 9].

Figure 9.

Fusiform aneurysm (*) of the left anterior descending coronary artery in a child with Kawasaki disease. Ao: aorta; LCA: left coronary artery; LAD: left anterior descending coronary artery

Echocardiography is the cornerstone of CAA diagnosis in children, allowing assessment of proximal CA dimensions and calculation of Z-scores. 3D echocardiography may offer incremental value in selected cases; however, limitations include suboptimal visualization of distal coronary segments and restricted acoustic windows.[52,53] Computed tomography coronary angiography provides a comprehensive evaluation of the coronary tree, particularly in cases involving distal aneurysms, branch vessel involvement, or inadequate TTE windows.

Coronary artery fistula

CA fistula (CAF) is a rare congenital anomaly in children, accounting for approximately 0.2%–0.4% of CHD. Most fistulas originate from the right CA and drain into right-sided cardiac chambers or the pulmonary artery, potentially resulting in coronary steal, chamber dilatation, or myocardial ischemia.[54] Echocardiography is the first-line diagnostic imaging modality, enabling identification of a dilated CA and a fistulous connection characterized by continuous, high-velocity Doppler flow at the origin and/or drainage site [Figure 10].

Figure 10.

Neonatal echocardiographic image demonstrating a right coronary artery (CA) fistula (*) arising from aorta and draining into the right ventricle. Note the dilated right CA. RCA: right coronary artery; AO: aorta; RV: right ventricle

Early detection is essential, as large or complex CAF may require transcatheter closure or surgical intervention to prevent long-term complications. Untreated large CAF may lead to heart failure, myocardial ischemia, arrhythmias, or aneurysm formation.

CONCLUSION

CA development is a highly complex and finely regulated process that begins early in embryogenesis and continues to evolve throughout fetal and postnatal life. Advances in prenatal imaging, particularly 2D and 3D ultrasonography with STIC and advanced flow-rendering techniques, have expanded the ability to visualize CA origins, courses, and diameters in selected fetal conditions. Although routine assessment of normal fetal CAs remains challenging, the identification of coronary abnormalities in the prenatal period may provide valuable insights into altered cardiogenesis, fetal hemodynamic compromise, and the risk of adverse neonatal outcomes.

In the postnatal setting, 2D echocardiography remains the cornerstone for the evaluation of CA anatomy and pathology, enabling early diagnosis of conditions such as anomalous coronary origins, CCA, and CAF. Accurate measurement techniques, standardized reference values, and integration with advanced imaging modalities are essential for risk stratification and longitudinal follow-up. A comprehensive understanding of CA embryology, physiology, and imaging across the fetal–neonatal continuum is fundamental to improving diagnostic accuracy, optimizing clinical management, and ultimately enhancing cardiovascular outcomes from early life into adulthood.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.