**2.1 Embryology**

The looping of the heart and the completion of the great vessels occur before the connection of coronary arteries to the aorta. Neural crest cells play an essential role in the outflow tract septation and coronary artery development. An additional element is the contribution of extracardiac cell populations like epicardium-derived cells. Coronary vascular formation occurs relatively late in development after covering of the myocardium by the epicardium. A plexus of epicardially derived vessels connects to the aortic root. It is generally considered that the initial segment of the coronary arteries develops by endothelial ingrowth from the peritruncal ring rather than by endothelial outgrowth from the aorta (Bogers et al., 1989). That is why the expression *anomalous connection* will often be used in this review. Otherwise, the concept of ingrowth permits a better understanding of the numerous ANOCOR patterns. Proximal left and right coronary arteries connect to the left posterior and anterior sinuses which are closest to the right ventricular outflow tract and pulmonary trunk. In the normal heart, the left posterior sinus is also known as the left sinus, and the anterior sinus, the right sinus. Recent experimental insights suggest that multiple endothelial strands penetrate the three sinuses at the onset of the proximal coronary vascular formation (Ando et al., 2004). Then, the left and the right stems develop by fusion of endothelial strands, and the strands connecting the right posterior sinus disappear. Therefore, the right posterior sinus is also known as the non-coronary sinus. Anomalous origin of coronary arteries may occur in isolation without abnormal myocardial outflow tract development. Inconsistencies exist with regard to the exact mode of development of these congenital abnormalities in otherwise normal hearts.

#### **2.2 Normal anatomy**

On an axial cross-sectional CT view, the origin of the left coronary arises at the 3- to 5 o'clock position and the right coronary at the 10- to 12-o'clock position (figure 1). Knowledge of the position of the heart within the mediastinum is essential for appropriate analysis of imaging tools (Anderson & Loukas, 2009). Due to the orientation of the aorta, the origin of the coronary arteries is not well visualised simultaneously on the same axial image. The left ostium is more cranial in comparison with the right ostium. Shortly after their origin, the coronary arteries run across the epicardial surface of the heart surrounded by fat. The proximal segment of the right coronary artery (RCA) courses directly in the right atrioventricular groove, whereas the left coronary artery (LCA) courses initially between the pulmonary trunk and the left appendage.

Today, prospective registries are ongoing in France and North and South America with the goal of assessing the natural history of ANOCOR, as well as the long-term impact of surgical repair or PCI. The present review will focus on recent imaging modalities allowing

The basics of cardiac development are needed to understand congenital coronary malformations and to avoid incorrect interpretation leading sometimes to erroneous

The looping of the heart and the completion of the great vessels occur before the connection of coronary arteries to the aorta. Neural crest cells play an essential role in the outflow tract septation and coronary artery development. An additional element is the contribution of extracardiac cell populations like epicardium-derived cells. Coronary vascular formation occurs relatively late in development after covering of the myocardium by the epicardium. A plexus of epicardially derived vessels connects to the aortic root. It is generally considered that the initial segment of the coronary arteries develops by endothelial ingrowth from the peritruncal ring rather than by endothelial outgrowth from the aorta (Bogers et al., 1989). That is why the expression *anomalous connection* will often be used in this review. Otherwise, the concept of ingrowth permits a better understanding of the numerous ANOCOR patterns. Proximal left and right coronary arteries connect to the left posterior and anterior sinuses which are closest to the right ventricular outflow tract and pulmonary trunk. In the normal heart, the left posterior sinus is also known as the left sinus, and the anterior sinus, the right sinus. Recent experimental insights suggest that multiple endothelial strands penetrate the three sinuses at the onset of the proximal coronary vascular formation (Ando et al., 2004). Then, the left and the right stems develop by fusion of endothelial strands, and the strands connecting the right posterior sinus disappear. Therefore, the right posterior sinus is also known as the non-coronary sinus. Anomalous origin of coronary arteries may occur in isolation without abnormal myocardial outflow tract development. Inconsistencies exist with regard to the exact mode of development of these congenital abnormalities in

On an axial cross-sectional CT view, the origin of the left coronary arises at the 3- to 5 o'clock position and the right coronary at the 10- to 12-o'clock position (figure 1). Knowledge of the position of the heart within the mediastinum is essential for appropriate analysis of imaging tools (Anderson & Loukas, 2009). Due to the orientation of the aorta, the origin of the coronary arteries is not well visualised simultaneously on the same axial image. The left ostium is more cranial in comparison with the right ostium. Shortly after their origin, the coronary arteries run across the epicardial surface of the heart surrounded by fat. The proximal segment of the right coronary artery (RCA) courses directly in the right atrioventricular groove, whereas the left coronary artery (LCA) courses initially between the

us to revisit previous concepts and definitions.

**2. Embryology and normal anatomy** 

diagnoses (Gittenberger-de Groot et al. 2005).

**2.1 Embryology** 

otherwise normal hearts.

pulmonary trunk and the left appendage.

**2.2 Normal anatomy** 

Fig. 1. Axial cross-sectional computed tomography views showing normal origin of the right coronary artery (arrow) and left coronary artery (arrow head).

Cardiologists and radiologists should be aware of the normal origin and anatomical variants (Angelini, 2007) of the coronary arteries (table 1) in order to make an accurate diagnosis of ANOCOR.


Table 1. Normal connections and anatomical variants of the coronary arteries. CX: circumflex, LAD: left anterior descending.

Proximal Anomalous Connections of Coronary Arteries in Adults 187

orientation of the initial pulmonary trunk, the origin of the LCA is hidden by the pulmonary trunk. Consequently, it is crucial to accept that the initial preaortic course of an ectopic coronary artery may be in contact with the subpulmonary infundibulum or pulmonary trunk or both. Thus, the definition of the so-called interarterial course is too simplistic in our opinion. Another major pitfall in this field is the confused anatomical interpretation of the space between the aortic and pulmonary roots. In fact, there is no muscular septum between the origins of the great vessels (Loukas et al., 2009). Therefore, the visualization of an ectopic coronary artery coursing between the subpulmonary infundibulum and the interventricular septum does not necessarily imply an intramyocardial course. The ectopic vessel passes rather on the myocardial septum and close to the subpulmonic infundibulum. Thus, for the reasons discussed above, we chose to identify 4 ectopic courses regarding their relationships with the great vessels: preinfundibular, retroinfundibular, preaortic and retroaortic courses, in opposition to the usual definition with 4 ectopic courses: prepulmonary, intraseptal,

At the level of the aortic and pulmonary valves, the aortic and pulmonary walls are in close contact surrounded by large fatty tissues. The adjacent area between the great vessels may vary according to age, intrathoracic deformations, and acquired heart diseases. A clockwise or counter-clockwise rotation of the aortic root can modify the relationship of a normal

So far, no consensus exists to define and classify easily the wide spectrum of the congenital coronary artery abnormalities (Angelini, 2002). Numerous, sometimes long or complex, descriptions have been presented in the literature (Angelini 2007, Dodge-Khatami et al., 2000, Jacobs & Mavroudis, 2010, Rigatelli et al., 2009, Roberts, 1986). We propose, in this review focused on the proximal anomalous connections of the coronary arteries, a simplified classification with 8 types (table 2). This classification is based on an anatomical view with the contribution of postmortem data (Frescura et al., 1998) and recent imaging modalities. By definition, the abnormalities involve the orifices of the LCA and RCA, and their branches. Different types of ANOCOR may be observed in the same patient. Diagnosis of ANOCOR is sometimes uncertain, especially in cases of an incomplete or poor-quality imaging. We consider that an accurate anatomical diagnosis should be the first step when an

interarterial and retroaortic courses (Roberts & Shirani, 1992).

**3. Classification** 

ANOCOR is suspected.

arteries.

coronary origin with the pulmonary trunk or subpulmonary infundibulum.

type I anomalous connection with the opposite sinus type II anomalous connection with the contralateral artery type III anomalous connection with the appropriate sinus type IV anomalous connection with the non-coronary sinus type V anomalous connection above the sinotubular junction

type VII anomalous connection with the pulmonary artery

Table 2. Simplified classification of proximal anomalous connections of the coronary

type VI single coronary artery

type VIII other abnormalities

In the normal heart, the coronary arteries arise from the upper half of sinuses, close to the sinotubular junction in most of cases (Muriago et al., 1997). A connection above the level of the sinotubular junction is possible. The coronary orifices are not always located in the centre of aortic sinuses. The left coronary ostium may lie near the junction between the left and right aortic sinuses, whereas the right ostium may lie near the junction between the right and the non-coronary aortic sinuses (Muriago et al., 1997). The discrimination between a common variant and an anomalous origin from an unusual site within the appropriate sinus is often difficult. It is inappropriate to use the notation of left and right aortic sinuses when there is an anomalous aortic origin of one of the coronary arteries. The categorisation proposed by the working group of Leiden (Gittenberger-de Groot et al., 1983) is based on the view by an observer positioned in the sinus farthest from the pulmonary trunk. The sinus at the right hand of the observer is named sinus 1 and gives rise to the right coronary artery in the normal heart, whereas the sinus at the left hand is named sinus 2 and normally gives rise to the left coronary artery. Another classification is used in this review with the two sinuses adjacent to the pulmonary trunk called respectively appropriate sinus and opposite sinus. The origin of mistakes that occur in the literature is often due to the confused interpretation describing the relationships of the ectopic coronary arteries with the adjacent structures, mainly the great vessels. The schematic representation, often cited, with a cross-section view of the aortic and pulmonary valves is erroneous. Indeed, the aortic and pulmonary annuluses are not in the same plane and the latter is more superior. Therefore, it is easy to understand that the initial path of the RCA is facing the subpulmonary infundibulum and not the pulmonary trunk (figure 2). According to the position and the

Fig. 2. Volume-rendered computed tomography image of the heart with the normal origin of the right coronary artery (white circle) marked. AO: aorta, LV: left ventricle, PT: pulmonary trunk, RA: right atrium, RV: right ventricle, SPI: subpulmonary infundibulum.

orientation of the initial pulmonary trunk, the origin of the LCA is hidden by the pulmonary trunk. Consequently, it is crucial to accept that the initial preaortic course of an ectopic coronary artery may be in contact with the subpulmonary infundibulum or pulmonary trunk or both. Thus, the definition of the so-called interarterial course is too simplistic in our opinion. Another major pitfall in this field is the confused anatomical interpretation of the space between the aortic and pulmonary roots. In fact, there is no muscular septum between the origins of the great vessels (Loukas et al., 2009). Therefore, the visualization of an ectopic coronary artery coursing between the subpulmonary infundibulum and the interventricular septum does not necessarily imply an intramyocardial course. The ectopic vessel passes rather on the myocardial septum and close to the subpulmonic infundibulum. Thus, for the reasons discussed above, we chose to identify 4 ectopic courses regarding their relationships with the great vessels: preinfundibular, retroinfundibular, preaortic and retroaortic courses, in opposition to the usual definition with 4 ectopic courses: prepulmonary, intraseptal, interarterial and retroaortic courses (Roberts & Shirani, 1992).

At the level of the aortic and pulmonary valves, the aortic and pulmonary walls are in close contact surrounded by large fatty tissues. The adjacent area between the great vessels may vary according to age, intrathoracic deformations, and acquired heart diseases. A clockwise or counter-clockwise rotation of the aortic root can modify the relationship of a normal coronary origin with the pulmonary trunk or subpulmonary infundibulum.
