**11. Pathophysiological mechanisms**

The degree of understanding of the pathophysiological mechanisms differs between the different types of ANOCOR.

### **11.1 Anomalous connections with the pulmonary artery**

For the first clinical description of an anomalous connection with the pulmonary artery (Bland et al., 1933), pathophysiological mechanisms were established and well understood (Edwards, 1964). In anomalous connections of the LCA with the pulmonary trunk, the most frequent abnormality, the left ventricular myocardium is initially fed by less saturated blood under high pulmonary vascular resistances. Then, the antegrade flow to the LCA decreases with an eventual reversal of flow due to the decrease in pulmonary vascular resistances, leading to a coronary steal phenomenon. A long asymptomatic period until adulthood is possible in patients with dominant RCA and multiple large intercoronary collaterals between RCA and LCA. However, permanent myocardial hypoperfusion progressively impairs left ventricular function with occurrence of dyspnea and/or heart failure in young age. Mitral insufficiency, generally mild or moderate, is frequent, due to papillary muscle ischemia. Hibernating myocardium is possible requiring myocardial viability studies in order to rule out idiopathic dilated cardiomyopathy. As aforementioned, low ventricular function and/or myocardial infarction sequelae may be the trigger for malignant ventricular arrhythmias revealing the coronary abnormality.

#### **11.2 Anomalous connections with the aorta**

In subgroups of anomalous origins from the aorta, mechanisms of life-threatening cardiac events are less clear. Even if most sudden deaths are almost due to ventricular fibrillation, the accurate sequence leading to lethal arrhythmic disturbance often remains unknown or debated. Hypotension and extreme bradycardia seem to occur before the malignant ventricular arrhythmia. Experimental studies are lacking in the field of ANOCOR. Numerous hypotheses have been speculated. The oldest of them, still often widely held, is the compression of the ectopic vessel between the aorta and the pulmonary artery. However, such mechanism has never been demonstrated. Extrinsic compression of the LCA in normal location, from a markedly dilated pulmonary artery trunk has been described (Caldera et al., 2009, de Jesus Perez et al., 2009, Lyndsey et al., 2008). Nevertheless, relationships between an ANOCOR with preaortic course and a non dilated pulmonary artery are different. As previously discussed, RCA or LCA with preaortic course are not necessary close to the pulmonary artery. Therefore, anatomical characteristics of ANOCOR with preaortic course and intramural segment are probably more interesting for comprehension of induced-myocardial ischemia (Angelini, 2007). It is important to consider that myocardial ischemia is not necessarily the result of significant differences between supply and demand of myocardial oxygen. In the absence of fixed atherosclerotic stenosis, the determinants of myocardial ischemia are not truly reproducible in patients with ANOCOR. Most young athletes are able to perform intensive and repetitive efforts which do not interfere with their performances until the occurrence of a life-threatening cardiac event. Thus, the subject continues to intrigue pathologists and physiologists. Invasive approach with IVUS advocated by Angelini et al. permitted a better comprehension between anatomical features of ectopic vessel and pathophysiological mechanisms of ischemia. If symptoms are a suggestive of a compressive etiology, one must consider IVUS as it is the

The degree of understanding of the pathophysiological mechanisms differs between the

For the first clinical description of an anomalous connection with the pulmonary artery (Bland et al., 1933), pathophysiological mechanisms were established and well understood (Edwards, 1964). In anomalous connections of the LCA with the pulmonary trunk, the most frequent abnormality, the left ventricular myocardium is initially fed by less saturated blood under high pulmonary vascular resistances. Then, the antegrade flow to the LCA decreases with an eventual reversal of flow due to the decrease in pulmonary vascular resistances, leading to a coronary steal phenomenon. A long asymptomatic period until adulthood is possible in patients with dominant RCA and multiple large intercoronary collaterals between RCA and LCA. However, permanent myocardial hypoperfusion progressively impairs left ventricular function with occurrence of dyspnea and/or heart failure in young age. Mitral insufficiency, generally mild or moderate, is frequent, due to papillary muscle ischemia. Hibernating myocardium is possible requiring myocardial viability studies in order to rule out idiopathic dilated cardiomyopathy. As aforementioned, low ventricular function and/or myocardial infarction sequelae may be the trigger for malignant ventricular

In subgroups of anomalous origins from the aorta, mechanisms of life-threatening cardiac events are less clear. Even if most sudden deaths are almost due to ventricular fibrillation, the accurate sequence leading to lethal arrhythmic disturbance often remains unknown or debated. Hypotension and extreme bradycardia seem to occur before the malignant ventricular arrhythmia. Experimental studies are lacking in the field of ANOCOR. Numerous hypotheses have been speculated. The oldest of them, still often widely held, is the compression of the ectopic vessel between the aorta and the pulmonary artery. However, such mechanism has never been demonstrated. Extrinsic compression of the LCA in normal location, from a markedly dilated pulmonary artery trunk has been described (Caldera et al., 2009, de Jesus Perez et al., 2009, Lyndsey et al., 2008). Nevertheless, relationships between an ANOCOR with preaortic course and a non dilated pulmonary artery are different. As previously discussed, RCA or LCA with preaortic course are not necessary close to the pulmonary artery. Therefore, anatomical characteristics of ANOCOR with preaortic course and intramural segment are probably more interesting for comprehension of induced-myocardial ischemia (Angelini, 2007). It is important to consider that myocardial ischemia is not necessarily the result of significant differences between supply and demand of myocardial oxygen. In the absence of fixed atherosclerotic stenosis, the determinants of myocardial ischemia are not truly reproducible in patients with ANOCOR. Most young athletes are able to perform intensive and repetitive efforts which do not interfere with their performances until the occurrence of a life-threatening cardiac event. Thus, the subject continues to intrigue pathologists and physiologists. Invasive approach with IVUS advocated by Angelini et al. permitted a better comprehension between anatomical features of ectopic vessel and pathophysiological mechanisms of ischemia. If symptoms are a suggestive of a compressive etiology, one must consider IVUS as it is the

**11. Pathophysiological mechanisms** 

**11.1 Anomalous connections with the pulmonary artery** 

arrhythmias revealing the coronary abnormality.

**11.2 Anomalous connections with the aorta** 

different types of ANOCOR.

gold standard anatomical technique. A slit-like orifice may have a large area, but can collapse with a valve-like manner, during an abrupt increase in pressure and/or volume in the aorta. Vessel hypoplasia is another potential cause of decrease in blood supply under extreme conditions. CT imaging and IVUS are useful to demonstrate a non atherosclerotic reduction of the lumen vessel in the initial ectopic path (figure 22). Another abnormality contributing to myocardial ischemia is the intramural segment of the ectopic vessel. Histology and ultrasonography demonstrated the non circular shape of intramural segment thoroughly. The oblong area of the latter may be more exposed to the dynamic changes of the aortic wall.

Fig. 22. Multiplanar reconstruction of computed tomography showing an hypoplasia of the initial path (arrow) of a right coronary artery arising from the left sinus. AO: aorta, RV: right ventricle.

If numerous anatomical risk factors were identified, the relative contribution of each factor is not clear. In a study, no significant differences were found in length of intramural segment, coronary ostial size, or angle of coronary take-off between right or left ANOCOR arising from the opposite sinus, with (n=12) and without (n=18) sudden death (Taylor et al., 1997). Age ≥ 30 years was the only factor with a lower incidence of sudden death. Apart from the fact that intensive exercises are preferably performed during the young age, the dramatic reduction of sudden death risk after the age of 30 years remains surprising. The progressive hardening of the aortic wall has been suggested as a pathophysiological mechanism, with less dynamic changes of the aortic media during exertion. Otherwise, clotting and spasm have often been suspected but rarely proven as further mechanisms leading to acute coronary events. Furthermore, large sequelae of transmural myocardial infarction are rare in necropsy cases. Nevertheless, chronic myocardial ischemic damage may occur and lead to fatal arrhythmias. Histologic examination of heart specimens of young athletes suffering from sudden death may show patchy replacement-type fibrosis (Basso et al., 2000) or scattered foci of contraction band necrosis (Corrado et al., 1992). CX coronary artery arising from the opposite sinus or the RAC is a well-known abnormality deemed benign. Nevertheless, suspicion exists about an earlier atherosclerotic formation in

Proximal Anomalous Connections of Coronary Arteries in Adults 219

ANOCOR is crucial before aortic surgery in order to avoid an injury of the ectopic vessel or

ACC/AHA 2008 guidelines for the management of adults with congenital heart disease (Warnes et al., 2008) give recommendations for congenital coronary abnormalities of ectopic aortic origin and for anomalous left coronary artery from the pulmonary artery (table 10).

Recommendations for congenital coronary anomalies of ectopic aortic origin

Recommendations for anomalous left coronary artery from the pulmonary artery

Table 10. ACC/AHA 2008 recommendations for anomalous connections with aorta and

Surgical repair is indicated for LMCA with preaortic course regardless of symptoms. Surgical repair is also indicated for RCA with preaortic course in association with symptoms and/or inducible ischemia. A conservative approach is recommended in asymptomatic in patients with ectopic RCA in association with preaortic course. Position of PCI with limited experience and without long-term follow-up is not established in the ACC/AHA guidelines. Furthermore, the risk stratification with age is not clearly exposed. Only, a young patient is

Class Level of

IIa C

IIb C

Class Level of

1 C

evidence

1

1

1

evidence

B

B

B

to compress along its course by a valvular prosthesis.

patients with any of the following indications:

vessels or in intramural fashion).

of ischemia.

pulmonary artery.

Surgical coronary revascularization should be performed in

between the aorta and pulmonary artery.

a. Anomalous left main coronary artery coursing

b. Documented coronary ischemia due to coronary compression (when coursing between the great

c. Anomalous origin of the right coronary artery between aorta and pulmonary artery with evidence

Surgical coronary revascularization can be beneficial in the setting of documented vascular wall hypoplasia, coronary compression, or documented obstruction to coronary flow,

Surgical coronary revascularization may be reasonable in patients with anomalous left anterior descending coronary artery coursing between the aorta and pulmonary artery.

In patients with an anomalous left coronary artery from the pulmonary artery, reconstruction of a dual coronary artery supply should be performed. The surgery should be performed by surgeons with training and expertise in congenital heart disease at centers with expertise in the

regardless of inability to document coronary ischemia.

management of anomalous coronary artery origins.

**12.2 Recommendations** 

the proximal path of ectopic CX coronary arteries. Angiographic demonstration of a reduction of the lumen is not rare. However, besides atherosclerotic narrowing, a distortion of CX coronary artery may also be suspected in case of enlarged aortic root due to their close relationships. The mechanism of a potentially higher incidence of CAD of ectopic CX coronary artery in the retroaortic segment remains unclear.
