**9. Clinical presentations**

ANOCOR are rarely recognized in infancy, except for anomalous connections with the pulmonary artery (Richard et al., 2005). Numerous clinical presentations are possible leading to the diagnosis of ANOCOR in young people and adults, but the situation seems different between < 30-year old and ≥ 30-year old. In populations with a known high prevalence of coronary artery and valvular diseases, the ANOCOR is usually diagnosed fortuitously during a selective coronary angiography. The clinical presentations are similar to those observed with symptomatic acquired heart diseases, and the association of an ANOCOR with a significant CAD is common. Sudden ANOCOR-related death is rare in such patients. Some ANOCOR may also be identified late in patients referred for evaluation of various atypical symptoms. In young populations, the latter can lead also to the diagnosis of ANOCOR. Nevertheless, serious symptoms usually related to exertion, are possible. Last but not least, a sudden death related to a high risk ANOCOR may be the first event in the life of a young patient. Fortunately, only a small subgroup of ANOCOR, including mainly anomalies with an intramural segment and anomalous connections with the pulmonary artery, may entail life-threatening adverse events. In patients with significant acquired heart disease, relationships between the coronary abnormality and clinical status should be made clear as far as possible. The clinical presentations of anomalous origins from the pulmonary artery differ from that of anomalous origins form the aorta.

#### **9.1 Sudden deaths**

210 Congenital Heart Disease – Selected Aspects

(Fujimoto et al, 2011, Schmitt et al. 2005, Rodriguez-Granillo et al, 2009). In a series of 28 patients with known ANOCOR (4 LMCA, 15 CX coronary arteries and 9 RCA), the origin and ectopic course was correctly identified in all patients (Ropers et al., 2001). All patients had had previously an X-ray coronary arteriography. A correct analysis was achieved in only 3 patients (11%) with the latter. Nine-teen ANOCOR in 12 patients were correctly analysed with CT angiography in another small series (Datta et al., 2004). Twelve ANOCOR (1 LMCA, 1 LAD coronary artery, 4 CX coronary arteries, 5 RCA and 1 single artery) in adults patients (mean age 63 years) were analysed retrospectively with invasive (11 patients) and non-invasive tests (Leddet et al., 2008). All ANOCOR were well identified with CT angiography. However, the interpretation of one photo is ambiguous in the paper with a listed preinfundibular course instead of a retroinfundibular course. Selective coronary angiography identified accurately the origin and the ectopic course of ANOCOR in 8 of 10 cases (80%) and in 2 of 10 cases (20%), respectively. The position of CT angiography cannot be ignored either before or after invasive coronary angiography. The latter and the CT imaging are complementary in most cases of ANOCOR in adult patients (Kim et al., 2006). The main characteristics of invasive and non-invasive imaging techniques are summarized in the table 8.

Characteristics TTE MRA CTA SCA IVUS Invasive no no no yes yes Ionizing radiation no no yes yes yes Iodine contrast media use no no yes yes no Spatial resolution (mm) 0.8 1.2 x 1.8 0.5 0.3 0.15 (axial) Visualization of adjacent structures ++ +++ +++ no no 3-D reconstruction no yes yes no no Visualization of orifice no + + + +++ Identification of intramural segment + + + + +++ Identification of ectopic course + +++ +++ ++ no Identification of CAD no + ++ +++ +++ (limited) Table 8. Comparison of imaging techniques in adult populations. 3-D: three-dimensional,

CAD: coronary artery disease, CTA: computed tomography angiography, IVUS: intravascular ultrasonography, MRA: magnetic resonance angiography, SCA: selective

Regarding to tomographic studies, the analysis of the literature shows non rare erroneous interpretations of ectopic courses of some ANOCOR, especially anomalous origins of LMCA or LAD coronary artery arising from the opposite sinus, with a misinterpretation between

ANOCOR are rarely recognized in infancy, except for anomalous connections with the pulmonary artery (Richard et al., 2005). Numerous clinical presentations are possible leading to the diagnosis of ANOCOR in young people and adults, but the situation seems different between < 30-year old and ≥ 30-year old. In populations with a known high prevalence of coronary artery and valvular diseases, the ANOCOR is usually diagnosed fortuitously during a selective coronary angiography. The clinical presentations are similar to those observed with symptomatic acquired heart diseases, and the association of an

coronary angiography.

**9. Clinical presentations** 

the preaortic course and retroinfundibular course.

Analysis of necropsy cases has been crucial to highlight the lethal risk of some ANOCOR (Frescura et al. 1998, Kragel & Williams, 1988). In a postmortem series of 242 congenital abnormalities of coronary arteries, 49 anomalous connections of the LCA and 52 anomalous connections of the RCA with the opposite sinus were identified (Virmani et al., 2001). Sudden death was observed in 57% of LCA abnormalities and 25% of RCA abnormalities. Most of them had a preaortic course. The profile of the patients suffered from sudden death is often typical: young age, frequent intensive exercise, and non systematic premonitory symptoms. In a necropsy study of 150 consecutive sudden deaths occurring in a population ≤ 35-year old, 16 sudden deaths related to non-atherosclerotic coronary disease were identified (Corrado et al., 1992). Three (19%) of them were ANOCOR (11, 22 and 29 year-old patients). Sudden death occurred during effort. In a series of 27 ANOCOR (23 LMCA and 4 RCA from the opposite sinus) identified at autopsy in young athletes, sudden death occurred during intense exertion in 25 cases or immediately after in 2 cases (Basso, et al. 2000). In 126 nontraumatic sudden deaths collected during a 25-year autopsy study of military recruits, there were 21 (17%) ANOCOR, all LCA originated from the opposite sinus, with a preaortic course (Eckart et al. 2004). Thus, sudden death, especially during exercise, is a fairly common mode of revealing high-risk ANOCOR in young populations. Some sudden cardiac arrests may survive up to hospitalization with public education and emergency care systems. The individual incidence of sudden death in asymptomatic patients with high risk ANOCOR remains unknown.

#### **9.2 Other symptoms**

All usual cardiac symptoms are possible, i.e. angina, chest pain, dyspnea, syncopes, palpitations. In autopsy studies mentioned above, prodromal symptoms before sudden death were noted in up to 56% of patients (Eckart et al., 2004) but often underestimated or hidden owning to the patient profile (athlete or military). In another study, only 55% of patients had no cardiac history (Basso et al., 2000). Syncope and chest pain, exercise-related almost without exception, are the most frequent symptoms However, it must be remembered that the population studied was subjected to extreme exercise, unusual for a general population. In the latter, symptoms leading to the diagnosis of ANOCOR are variable and sometimes no such typical with chest discomfort or palpitations. Obviously, stable angina and acute coronary syndromes are possible if a significant CAD is associated. In a retrospective study, 301 anomalous origin from the opposite sinus were identified among

Proximal Anomalous Connections of Coronary Arteries in Adults 213

resting ECG is unable to identify young people with ANOCOR except some anomalous connections in pulmonary artery (Cohen & Berger, 2010). Exercise stress test, with a known low sensibility in symptomatic high risk ANOCOR, is clearly inadequate for screening of an asymptomatic population. Among non-invasive imaging tools, ETT has the potential to identify some ANOCOR. Nevertheless, capacity for ETT should be dramatically increased and cardiologist should be trained to visualize coronary ostia. Meanwhile, better information among young athletes of frightening cardiac symptoms, i.e. chest pain or syncope in exertion, appears probably as a useful preventive measure to reduce the calamitous impact on the well-know sport benefits of each exercise-related sudden death. In addition, the visualization (or at least a meticulous search for) of origins of coronary arteries should be a routine part of any echocardiographic procedure in young population referred for functional assessments. Recently, the first series of familial ANOCOR was published with identification of 5 families in which a child or a young person <30-year old was diagnosed with preaortic ANOCOR generally symptomatic and another family member was identified with a preaortic ANOCOR through echocardiographic screening (Brothers et al., 2008). A systematic TTE screening for children and young people in families with a history of a major cardiac ANOCOR-related event (sudden death or aborted sudden death)

It is insufficient to note an abnormal origin of a coronary artery. A complete diagnosis with the orifice and the course of the ANOCOR will allow an accurate prognostic stratification. Risk identification is a major stage after a diagnosis of ANOCOR, because important therapeutic decisions and restrictive recommendations on lifestyle may follow from the final classification of the coronary abnormality. Usually, ANOCOR are identified at low-risk or high-risk with a strong evaluation criterion (sudden death). Nevertheless, one have to keep in mind that low-risk does not signify no risk. This classification is based first on postmortem examinations, because many of the patients with high-risk ANOCOR were previously diagnosed at autopsy. Now, with a better knowledge of these abnormalities and the development of imaging tools allowing an early diagnosis, it is mandatory that cardiologists and radiologists be familiar with the spectrum of congenital coronary abnormalities and their potential clinical relevance. However, the angiographers may be faced with difficult decisions for example a symptomatic patient with a low-risk ANOCOR or an asymptomatic patient with a high-risk ANOCOR. So far, no solid data are available on the natural history of ANOCOR with abnormal origin from the aorta. Several characteristics and parameters allow evaluation of sudden-death risk in most ANOCOR. However, in some cases, the classification may be difficult, and without enough information, it seems preferable to avoid too strict therapeutic rules. Indeed, it is always intriguing and not clear that among patients with the same high-risk ANOCOR, some will suffer from early sudden

Despite its rare frequency, the natural history of anomalous connections with the pulmonary artery is better known, and the latter are classified as high-risk. The risk of sudden death is related to malignant arrhythmias or acute myocardial infarction. Progressive left ventricular dilatation and dysfunction secondary to chronic myocardial ischemia is the trigger for rhythmic disturbances occurring usually before 35 years of age. The main subgroup of high-

death, while others will die later in life of unrelated cause .

**10.2.1 Type of coronary abnormality** 

may be discussed.

**10.2 Risk identification** 

210,700 adult patients underwent selective coronary angiography (Krasuski et al., 2011). The mean age (58 ± 14 years) was relatively high in the ANOCOR cohort. As presenting symptoms, chest pain and dyspnea were common (66% and 58% of patients, respectively), as well as a myocardial infarction (24% of patients). However, the prevalence of significant CAD was of 68% in this population. Clinical presentations similar to CAD-related presentations are possible in ≥ 50-year old patients free of significant CAD (Angelini et al., 2006).

### **9.3 Anomalous connection with the pulmonary artery**

The clinical presentation of anomalous connections with the pulmonary artery is different in children and adult populations. The mortality rate is high in infancy. In anomalous connection of the LCA with the pulmonary artery, an intermediate survival is possible with a major enlargement of the RCA and multiple intercoronary collaterals. In patients who survive into childhood, left ventricular enlargement and/or dysfunction, mitral valve incompetence, heart failure, myocardial infarction, or ventricular arrhythmias are reported, usually before 35 years age. Dyspnea and/or angina on exertion are the most frequent presenting symptoms (Kottayil et al., 2011). However, sudden death due to malignant ventricular arrhythmias may be the first cardiac event (Frapier et al., 1999). Fortuitous discovery is rare in asymptomatic patients with a continuous murmur due to interventricular collateral flow.
