Over the many decades since the first surgical repair for patent arterial duct,Reference Gross¹ the outpatient management of the multitude of congenital cardiac defects has been increasingly defined.Reference Wernovsky, Rome and Tabbutt^2–Reference Boris⁵ The therapy both in the outpatient setting as well as within the operating room, although not completely settled, is by and large agreed upon; however, there are still several congenital cardiac lesions for which the decision-making process regarding surgical intervention as well as outpatient management remain less defined. One of these lesions includes the congenital anomalies of the coronary arteries. This includes a heterogeneous group of findings within the coronary arteries: the more historically known lesion, anomalous left coronary artery arising from the pulmonary artery,Reference Bland, White and Garland⁶ is joined by the anomalous right coronary artery arising from the pulmonary artery, and the circumflex artery arising from the pulmonary artery. Nevertheless, the increasingly recognised and more acutely dangerous lesions include anomalous aortic origin of a coronary artery; this can be either the left coronary artery arising from the right coronary sinus or the right coronary artery arising from the left coronary sinus. These typically have the highest risk when they course between the two great arteries and often have an intramural component to them. The remainder of the coronary anomalies include coronary artery fistulae, atresia or stenosis of the ostium of the coronary artery, and myocardial bridges, the last of which will not be addressed in this article.

As with the diversity of the lesions, so is the diversity of their presentation. The classic presentation for patients with anomalous coronary artery arising from the pulmonary artery occurs in the infant who demonstrates not only dyspnoea and diaphoresis with feeding but also associated crying, indicating that the infant is experiencing significant pain, likely consistent with angina pectoris. These symptoms usually resolve upon stopping feeds, after which the infant would then usually wish to eat again, with resumption of symptoms with re-feeding. They can also present with wheezing and a diagnosis of cardiac asthma. The more terrifying presentation, also more noted in the news media, occurs when these patients have an initial presentation of sudden cardiac death, which may occur when one or both coronary arteries arise from the wrong aortic sinus. More frequently, however, these anomalies typically present as undiagnosed findings incidentally noted on echocardiographic studies. These studies are obtained for various reasons, such as for the evaluation of some other cardiac concern, or specifically for the evaluation of an abnormal event, suggesting a coronary aetiology – for example, an exercise-induced event or an event suggestive of angina pectoris. It is interesting to note that routine pre-participation athletic screening evaluations are notorious for not detecting these lesions during assessment of history, physical examination, electrocardiography, and exercise stress testing. Historical features of chest pain, dizziness, or syncope at rest, which are more frequently seen in the outpatient setting, are not consistent with the presence of a coronary anomaly. Yet, there are “red-flag” symptoms and clinical findings that are suggestive of anomalies of the coronary arteries. These include symptoms associated with exercise, such as chest pain, dizziness, and syncope specifically during or just after exercise, as opposed to those that occur solely at rest. In addition, ventricular arrhythmias, cardiomyopathies, myocardial infarction, and sudden cardiac death, whether aborted or complete, should suggest to the cardiologist the presence of a coronary lesion.

The physical examination of patients with coronary anomalies depends on whether haemodynamic changes secondary to disturbed flow or abnormal myocardial perfusion are present. Most frequently, as suggested above, the physical examination is normal. Larger coronary artery fistulae can create a continuous murmur with diastolic accentuation occurring over the heart. This should be contrasted with the venous hum, which also generates a continuous murmur with diastolic accentuation, but is located at the upper right or left borders of the sternum, and disappears with supine position, with jugular venous compression, or with head turn. The more concerning findings on physical examination occur in the presence of dilated cardiomyopathy secondary to ischaemia of the myocardium. These findings include the following: an active praecordium, leftward and/or downward displacement of the apical impulse, the presence of an S4 gallop at the apex, and the presence of a systolic murmur of regurgitation heard at the apex and potentially radiating to the left axilla or to the lower left border of the sternum, consistent with regurgitation of the mitral valve. Cardiac asthma, or congestive heart failure creating respiratory symptoms, can be indicated by the presence of expiratory wheezing in addition to tachypnoea and cough. There can be hepatomegaly if the heart failure is severe enough to cause failure of both the left and right ventricles. In addition, peripheral oedema can be noted, although this is not common.

Routine ancillary testing of these patients, as previously mentioned, is also often normal. Electrocardiography, as a screening test, is rather inadequate for the majority of these patients, as changes that would suggest a coronary aetiology occur either late, or when symptoms are severe, or still not at all. Those findings that can be seen are suggestive of ischaemia or infarction, including regional ST segment changes, inversion of T-waves, or poor progression of the R waves across the praecordium. This last finding is also called an R-wave “electrical window”, in which the amplitude of one or more of the mid-praecordial R-wave is significantly and inappropriately truncated in comparison with those of its neighbouring leads. Performance of stress testing also routinely demonstrates normal findings, although exercise-induced chest pain can occur. Ischaemic ECG changes can be induced, such as depression of the ST segments in either a horizontal or a downsloping direction for greater than 1 mm and lasting for more than 60 to 80 milliseconds. Malignant ventricular arrhythmias can also occur during exercise testing, but are infrequent, as both of these exercise-associated ECG findings are findings seen later in the course of disease. In fact, as noted by Kimball,Reference Kimball⁷ tests more likely to demonstrate evidence of coronary lesions include positron-emission testing and radioisotope perfusion scanning, tests not routinely performed unless there is a strong suggestion or demonstration of the presence of coronary disease (Fig 1).

Figure 1 Evolution of ischaemia and clinically applicable tests. From KimballReference Kimball⁷.

The diagnostic test that is most commonly performed for the evaluation of a potential coronary anomaly is echocardiography; two-dimensional imaging demonstrates many of the important findings necessary for the diagnosis of a coronary lesion. This includes the anatomy of the coronary artery as well as secondary findings such as echogenicity of the myocardium and papillary muscles, abnormal wall motion of the left ventricle, decreased systolic function, and dilation of the left ventricle. The addition of colour Doppler can further define the anatomy of the coronary arteries as well as demonstrate the flow direction or the presence of stenosis of the artery. Fistulae can be visualised, as well as the demonstration of regurgitation of the mitral valve secondary to ischaemia of the left ventricle. Tissue Doppler imaging is a supportive finding that shows evidence of dysfunction of diastolic inflow in the face of myocardial damage. Diastolic dysfunction often precedes other, more advanced indicators of damage, such as systolic dysfunction and ventricular dilation. Finally, although infrequently used, spectral Doppler can also demonstrate the direction and velocity of flow within the coronary arteries as well as show estimated gradients across stenotic regions.

When a diagnosis of an anomaly of the coronary arteries is made by echocardiography, confirmatory or supplementary evaluation is strongly suggested. Although echocardiography is good at determining the anatomy of the coronary arteries, it may not always show the exact anatomical features or the myocardial effects of hypoperfusion. Thus, other tests can help with this. An option for anatomical evaluation is magnetic resonance imaging (MRI) of the heart with or without adenosine stress testing. It can further delineate the course of the coronary arteries, although the images may not be as sharp as those seen with computed tomography (CT). MRI also can show the full extent of a dilated cardiomyopathy, especially if the acoustic windows in the patient’s chest are poor. The use of delayed enhancement with gadolinium perfusion can demonstrate scarring of the myocardium, as well. CT scanning can give very precise images of the coronary arteries, including their origins, courses, and collateralisation, but cannot evaluate for myocardial scar, plus it exposes the patient to ionising radiation. For functional assessment, one option is the use of either exercise-stress or dobutamine-stress echocardiography; however, there are some recent data suggesting that the positive predictive value of exercise-stress and dobutamine-stress echocardiography may be too low to detect regional wall motion abnormalities with poor pre-test probability.Reference Wood and Thompson⁸ Scanning using positron-emission tomography is used to assess defects in the uptake of a radioisotope, thus showing evidence of damage to the myocardial cells, but this is not a readily available test for the paediatric population. Nuclear medicine scanning is also a method used to assess the systolic function of the left ventricle as well as to evaluate myocardial perfusion at rest versus with stress. The disadvantage of these latter two modalities is the use of ionising radiation, which limits their routine use. Finally, cardiac catheterisation is another potential tool for evaluation; however, it is more invasive, does not assess perfusion adequately, and also utilises radiation as part of its imaging.

Once an anomaly of the coronary artery is suspected, one of the biggest questions occurs in those patients who may be either asymptomatic or who may have modest symptoms without other clinical findings: can this patient be allowed to exercise competitively? In the absence of good data, there have been multiple attempts to create a reasonable decision tree. At our institution, we utilise a schema, as noted in Fig 2, specifically for patients with anomalous aortic origin of the coronary artery. This takes into account the use of confirmatory testing and perfusion imaging as well as the presence or absence of symptoms.

Figure 2 Decision tree used at the Children’s Hospital of Philadelphia for allowing a patient with anomalous aortic origin of the coronary artery to participate in competitive exercise. AAOCA=anomalous aortic origin of the coronary artery; CMR=cardiac magnetic resonance imaging; CT=computed tomography; LCA=left coronary artery; RCA=right coronary artery.

The next question to follow this is whether surgery, or other intervention, is indicated. In those patients with anomalous left coronary artery arising from the pulmonary artery, surgical intervention to create a two-coronary artery repair is indicated. If it is detected in a timely manner, the cardiomyopathic changes as well as the regurgitation of the mitral valve can reverse; however, residual ischaemic cardiomyopathy and some aspect of valvar regurgitation may persist in these patients. It is not known whether the ischaemic scarring within the cardiomyopathy disappears or acts as a nidus for potential ventricular arrhythmias in the future. Patients with an anomalous right coronary artery or the circumflex coronary artery arising from the pulmonary artery tend not to be diagnosed as early as those patients with an anomalous left coronary artery, as the clinical findings are less severe or absent. Although collateralisation has often occurred, surgical repair with re-implantation of the coronary artery to remove any potential for steal is still indicated.

Patients with anomalous aortic origin of a coronary artery have been demonstrated to have an increased incidence of sudden cardiac death. Those patients with an anomalous left coronary artery from the right coronary sinus have a clear association with sudden cardiac death,Reference Roberts^9–Reference Frescura, Basso and Thiene¹¹ with the majority of patients experiencing exercise-induced sudden death having been previously asymptomatic. Thus, although these are much less frequently seen, there is a clear indication that these patients should have surgical revision of their coronary ostium. For patients with anomalous right coronary artery arising from the left coronary sinus, the risk of sudden cardiac death is significantly less, but it is not zero. Therefore, in this more frequently seen lesion – compared with its opposite lesion as mentioned above – there has been debate as to whether surgical intervention is required. To be sure, as the risk of sudden death is not zero, there is often a parental interest in having the surgery performed, notably if the patient is a competitive athlete. In the absence of participation in competitive sports, as the risk of sudden death is exceedingly low, the risk of complications from surgery likely outweighs the risk of a sudden death event occurring. The schema for decision for evaluation and intervention is shown in Figure 2.

Coronary artery fistulae are the most commonly seen congenital anomaly of the coronary arteries, noted in up to 50% of all congenital coronary lesions. The natural history of small lesions is that they are haemodynamically insignificant, do not grow, and can occasionally spontaneously resolve;Reference Said, Lam and van der Werf^12, Reference Ceresnak, Gray and Altmann¹³ however, larger fistulae impart a risk of myocardial infarction, congestive heart failure, endocarditis, and rupture of the artery if there has been formation of an aneurysm. In these defects, either surgical or transcatheter intervention can resolve these shunts.Reference Said, Lam and van der Werf^12, Reference Ceresnak, Gray and Altmann¹³ Finally, in those arteries in which there is stenosis or atresia of the coronary ostium, they are typically collateralised. Intervention is usually not undertaken as long as there is no evidence of angina or scarring. Of note, involvement of the left coronary artery in this defect is seen more than that of the right coronary artery.Reference Angelini¹⁴

Irrespective of whether a patient has undergone surgical intervention, follow-up of these patients is crucial. An attempt at assessment of new or ongoing risk of myocardial damage should be considered. Owing to this, the follow-up should be long term. At minimum, electrocardiography and echocardiography should be performed, keeping in mind the limitations of these tests, as discussed above. Exercise stress testing should be carried out, with the frequency depending on the patient’s activity level. It should be carried out, at least occasionally, in conjunction with either stress echocardiography or perfusion imaging. Stress echocardiography can be used for symptom evaluation, although there is no good data to demonstrate its utility in the post-operative evaluation of these patients. Meanwhile, the risk of radiation exposure with perfusion imaging needs to be taken into consideration, as well. Cardiac MRI can assess the formation of myocardial scarring. There is an increased risk of stenosis of the neo-ostium if it has been manipulated with surgical intervention. Thus, MRI can also be used to assess for recurrent obstruction of the neo-ostium.

Finally, independent of whether a patient undergoes intervention, the most important issues to address are the risk of sudden cardiac death in association with exercise, whether exercise can be allowed, and in what form can exercise be allowed. These recommendations are summarised in Table 1. They are, in part, based on the 36^th Bethesda Conference recommendations for competitive athletes with cardiovascular abnormalities;Reference Maron and Zipes¹⁵ however, there have been rare case reports of sudden cardiac death in patients who have had operative repair of this lesion. Therefore, if the patient’s initial presentation was an aborted event of sudden cardiac death, competitive exercise may not be recommended. In addition, caution should be used in patients with anomalous aortic origin of the coronary artery who have undergone manipulation of their arterial ostium. Subclinical changes suggestive of ischaemia have been noted in these patients, despite a widely patent neo-ostium; these have been most notably seen in patients after repair of the anomalous right coronary artery arising from the left sinus. The risk for subsequent myocardial ischaemia or sudden cardiac death in these patients is unknown.

Table 1 Suggested athletic participation guidelines for patients with coronary artery anomalies.

The limitation of physical activity to only recreational participation in asymptomatic patients with an anomalous left coronary artery with an interarterial course under the age of 10 years is based on the lack of evidence in these patients having sudden cardiac death under the age of 10 years. Children tend not to exercise as vigorously as their adolescent or adult counterparts, although care should be taken in those older children who may attempt to participate in a more rigorous manner to keep up with their older peers.

Finally, two other issues pertaining to the long-term management of these patients in the clinic merit discussion. The first regards counselling for risk of recurrence in families. Although there are isolated case reports in which more than one family member has an anomaly of the coronary arteries,Reference Laureti, Singh and Blankenship^16–Reference Bunce, Rahman, Keegan, Gatehouse, Lorenz and Pennelli¹⁸ overall there has been no consistent demonstration of an increased risk of recurrence of this family of lesions in first-degree relatives; families should be informed of this information. The second issue also pertains to counselling these patients and families; there is no requirement for antibiotic prophylaxis for infective endocarditis in patients with congenital anomalies of the coronary arteries either before or after surgical intervention. As the flow in the coronary arteries is of low velocity, the risk for denudation of the endothelium with exposure of basement membrane proteins that could allow for thrombosis is low as well, and makes the overall risk low. Therefore, the only indication for antibiotic prophylaxis is the presence of a history of previous endocarditis or another high-risk cardiac lesion, as listed by the American Heart Association.Reference Wilson, Taubert and Gewitz¹⁹

In all, congenital lesions of the coronary arteries, although usually clinically silent, have the potential to cause severe myocardial damage and sudden cardiac death. Many of the recommendations for care discussed in this document are based on the best data available at present. It is hoped that, with the advent of the Congenital Heart Surgeons’ Society registry for anomalous aortic origin of the coronary artery,Reference Brothers, Gaynor and Jacobs²⁰ further data can be obtained in order to be able to create an evidence-based approach towards surgical decision making, long-term outpatient follow-up, and activity recommendations for these patients.

Addendum

Since the writing of this manuscript, a new American Heart Association/American College of Cardiology Scientific Statement was published (Van Hare et al) regarding competitive sports participation in those with cardiovascular abnormalities. Regarding coronary anomalies, this Statement takes into account the much lower risk of sudden cardiac death associated with competitive sports in those with interarterial anomalous right coronary artery when compared with interarterial anomalous left coronary artery. The Statement now suggests that those with anomalous right coronary artery who are asymptomatic and have a negative exercise stress test for ischemia may participate in competitive athletics, after discussion with the patient and his or her family about the risks of sports participation with this anomaly. The recent Scientific Statement did not make any other changes in recommendations for sports participation with the other types of coronary anomalies.

Reference: Van Hare GF, Ackerman MJ, Evangelista JK, Kovacs RJ, Myerburg RJ, Shafer KM, Warnes CA, Washington RL; on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and the American College of Cardiology. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 4: congenital heart disease: a scientific statement from the American Heart Association and American College of Cardiology. Circulation. 2015; published online before print November 2 2015, doi:10.1161/CIR.0000000000000240.