Congenital or acquired coronary artery anomalies are not infrequently diagnosed in children and adolescents, many of whom actively participate in routine exercise and/or competitive sports. These anomalies include anomalous aortic origin of a coronary artery (AAOCA), myocardial bridge or intramyocardial coronary artery, anomalous origin of the right or left coronary artery from the pulmonary artery, and sequelae of Kawasaki disease. This review focuses on AAOCA, the second leading cause of sudden cardiac death (SCD) in young US athletes1 and a condition that poses challenges to risk stratification and optimal patient management.
AAOCA is a congenital abnormality of the origin or course of a coronary artery that arises from the aorta. This condition is associated with SCD, especially when the anomalous coronary originates from the opposite sinus of Valsalva. The clinical manifestations of patients presenting with AAOCA are quite variable, ranging from evident myocardial ischemia, such as angina-like chest pain and sudden cardiac arrest (SCA), to complete lack of symptoms. The exact mechanisms leading to SCA or SCD and the absolute determinants of risk are not completely understood. Risk stratification is frequently determined through myocardial functional studies to assess for evidence of inducible ischemia during provocative testing. Some patients may require invasive assessment with cardiac catheterization, including intravascular ultrasound (IVUS) and measurement of fractional flow reserve (FFR).
For the past 5 to 10 years, many efforts have advanced the knowledge about AAOCA, including specific anatomic types, diagnostic evaluation with imaging and myocardial functional assessment, and management strategies.2,3 For the last several years, speakers from leading institutions have held dedicated scientific forums to discuss coronary anomalies. It is believed that prospective data gathering, longitudinal follow-up, and accrued experience will lead to better understanding of this condition and will directly benefit counseling and shared decision making with patients and families affected by AAOCA. This review highlights the current knowledge around AAOCA and serves as a general guide for clinicians.
SUDDEN CARDIAC DEATH
Sudden cardiac death leads to substantial anxiety in schools, sports organizations, and communities in general, especially because most events occur unexpectedly in healthy children or young athletes during or immediately after exercise.1,47 Quite often, SCD is the first symptom of underlying cardiac disease. The risk of SCD in athletes is estimated at between 0.5 and 1 per 100,000 athlete-years,8 though more recent studies have reported a higher incidence in specific populations.9 However, the risk for all young individuals may be much higher. For example, the Resuscitation Outcomes Consortium reported an incidence of 8 cardiac arrests per 100,000 person-years in individuals under 21 years of age.10
Data from National Collegiate Athletic Association athletes have shown that SCD accounts for 16 of deaths compared to accidents (51), suicides (9), and homicides (6).9 The most common cause of SCD was notably unknown in 31 of these athletes followed by anomalous coronary arteries in 14; interestingly, hypertrophic cardiomyopathy (HCM), dilated nonischemic cardiomyopathy, and myocarditis each accounted for 8. By contrast, data from the US National Registry of Sudden Death in Athletes shows that the most frequent related causes were HCM (36), congenital coronary anomalies (19), indeterminate with left ventricular hypertrophy (9), and myocarditis (7).11 In military recruits, the SCD incidence appears higher (13 per 100,000 person-years), with anomalous coronary arteries reported in 33, myocarditis in 20, and HCM in 13.12 Males appear to be more likely to suffer SCD than females,13 and nonwhites are overrepresented in SCD registries compared to whites.1 In fact, most recent studies have suggested a higher occurrence of SCD in the black race, with no known reason.9,11,13
Unquestionably, congenital coronary anomalies are among the most frequent causes of SCD in youth. An increasing number of anomalies are being incidentally found on imaging studies that are done for preparticipation evaluations, for other common reasons (such as presence of a murmur or an abnormal electrocardiogram), or as part of screening programs to detect cardiovascular conditions possibly associated with SCD, as is currently ongoing in Texas with cardiac magnetic resonance (CMR) imaging.14,15 About 75 of SCDs are related to a cardiovascular etiology. They usually occur during or after exercise and are most commonly associated with dynamic exercise.1
The pathophysiological mechanisms that predispose individuals to SCD, the risk conferred by different anatomical subtypes, and the effect of current treatment strategies on reducing SCD risk are not fully known. Several pathophysiological mechanisms have been postulated to lead to SCA or SCD in those with AAOCA, including the presence of coronary ostial abnormalities, compression of an interarterial segment between the great vessels, compression of an intramural segment during exercise, and obstruction by a flap-like ridge related to an acutely angulated coronary arteryall leading to myocardial ischemia and development of ventricular arrhythmia.1618 However, it is not fully understood what ultimately leads to a sudden cardiac event given that these patients often performed similar levels of exercise for many years without symptoms.
ANATOMY AND NOMENCLATURE
AAOCA is the abnormal origin of one or more coronary arteries from the aorta, and it encompasses a wide spectrum of anatomical variations. Despite an increased understanding about this pathology, it is unclear which pathophysiological mechanisms are related to SCD and which types of AAOCA confer the highest risk. Due to the wide anatomical variability, a systematic description of the anatomy is necessary to get a better understanding of AAOCA.19
The topographic location of the ostium can be described using the circumferential location and height of the ostium. Figure 1 depicts a proposed system to describe the precise location of each coronary ostium with respect to the sinuses and commissures of the aorta. Based on this nomenclature system, the normal right coronary artery arises from a 1b-I location whereas a normal left coronary artery arises from a 2b-I location. In our experience, the vast majority of AAOCA variants appear to arise high and on the opposite side of the intercoronary commissure (ie, location 2a-III/IV for an anomalous right coronary and location 1c-III/IV for an anomalous left coronary). Additional coronaries can be described in a similar fashion, such as an anomalous circumflex arising directly from the aorta.
The spatial relationship between two coronary ostia is important as it may determine whether both coronary vessels represent branches from a single coronary or two completely separate vessels. The ostial relationship can be graded from grade 1 (separate coronary arteries) to grade 4 (single coronary artery with separate branches) (Figure 2).
Almost all anomalous coronaries have to take a more angled course proximally as the vessel travels to its destination. In simple terms, a coronary ostium can be described as round, slit-like (if the anteroposterior dimension is shorter than the superoinferior dimension), and/or stenotic (if the ostium is smaller than the distal coronary).
The interarterial segment of a coronary artery travels between the aorta and the pulmonary artery. An intramural segment travels within the wall of the aorta before arising from it. An intramyocardial coronary segment is said to be present when the vessel is completely surrounded by myocardium. Myocardial bridges, where the coronary is surrounded by myocardium after having had an initial epicardial course, are a relatively common type of intramyocardial coronary. An unusual variant of an intramyocardial vessel is the intraseptal anomalous left coronary artery. This is usually characterized by a single coronary artery arising from the right sinus (or an anomalous left coronary artery arising from the right sinus), with the left coronary diving into the interventricular septum below the level of the pulmonary valve (and behind the right ventricular outflow tract). The anomalous vessel will usually resurface lateral to the pulmonary artery before bifurcating into the anterior descending and circumflex branches.
The Intercoronary Pillar
An underappreciated anatomical feature of the aortocoronary complex is the intercoronary pillar, which is a thickening of tissue that extends cranially from the intercoronary commissure up to the sinotubular junction; it can be quite thick in some patients (Figure 3). This pillar likely contributes to the support of the aortic valve. Furthermore, we believe that this thick structure may play a significant role in compressing the anomalous coronary traveling behind it. As such, any surgical intervention performed to treat AAOCA should aim to alter the anatomy such that the ostium is appropriately away from the intercoronary pillar.
DIAGNOSIS AND EVALUATION
An increasing number of children and adolescents are being diagnosed with AAOCA following routine pre-participation screening, detection of a murmur, or an abnormal electrocardiogram (ECG) rather than during evaluation of symptoms. Evaluation prompts additional imaging, typically an echocardiogram, and the suggested diagnosis of AAOCA is then confirmed by advanced imaging, ie, computerized tomoraphy angiography (CTA) or CMR.
Patients with AAOCA may present with variable degrees of symptoms, although half are asymptomatic upon presentation. Concerning symptoms include chest pain (especially on exertion), dyspnea, palpitations, and syncope (especially on exertion).1,5,11,13,18 In a study by Basso et al. of 27 individuals who experienced SCD due to AAOCA, only 10 presented with symptoms prior to the event.5 An acute angle of take-off and slit-like ostium was evident in all 10 cases. In a series published by Eckart et al., 52 of military recruits who experienced SCD reported previous symptoms of chest pain, dyspnea, and syncope.12 In our experience with AAOCA, 51 of patients were asymptomatic, 29 had chest pain, 15 had syncope, and 3.3 presented with SCA.20 Of those presenting with SCA, one had a previous diagnosis of asthma and used his inhaler when he felt short of breath during exercise, one had been evaluated for syncope following exertion that was deemed vasovagal in nature, and two were completely asymptomatic.
Cross-sectional imaging by CTA or CMR is necessary to confirm the diagnosis and, more importantly, to accurately define the anatomy of the anomalous vessel, including interarterial and/or intramural course, intraseptal or intramyocardial course, and ostial morphology.
Coronary CTA provides precise spatial resolution with excellent definition of ostial morphology and location of the anomalous coronary artery's proximal course (Figure 4). Moreover, it does not require sedation in younger children, and the amount of ionizing radiation has significantly decreased with new-generation scanners. The protocol includes retrospective ECG-gated dynamic CTA of the heart, and images are post-processed using a 3-dimensional (3D) workstation, with virtual angioscopy providing great details of ostial morphology. The presence and length of intramurality is obtained by analyzing the morphology of the proximal coronary artery, including the diameter of the vessel as it is laterally compressed in its intramural segment and the presence or lack of pericoronary mediastinal fat.21 Coronary CTA is our preferred modality for advanced imaging after an initial diagnosis by echocardiography.
Some institutions prefer CMR imaging because it does not use ionizing radiation and provides accurate data on myocardial perfusion and viability, function, and flow patterns. However, this modality often requires sedation in younger children and lacks the spatial resolution needed to determine ostial morphology and course of the anomalous vessels.
Myocardial Functional Assessment
Exercise stress test (EST) is universally used to evaluate these patients, but there is controversial data regarding its validity. Studies have reported that 6 to 22 of patients who undergo surgery or experience SCD present with an abnormal EST.5,22,23 In our program, 8 of patients have an abnormal EST.23
Imaging with nuclear perfusion stress (NPS) is typically used to evaluate myocardial perfusion; however, this technique is marred by false positive and false negative results, thus affecting its reliability to truly identify myocardial ischemia.
Abnormal perfusion defects with this technique have been reported in patients with AAOCA, including following surgical intervention.22 We have observed similarly poor reliability with NPS compared to stress CMR, with sensitivity of only 33.24
Stress CMR imaging with pharmacologic agents has demonstrated superiority to NPS in assessing myocardial perfusion in patients with AAOCA.24 This technique appears to be feasible, safe, and well tolerated in the pediatric population.24 It also reliably detects perfusion defects and wall motion abnormalities, which contributes to risk stratification in these patients.
Although cardiac catheterization is primarily used in the adult population, it recently has been shown to be feasible and safe in pediatric patients with AAOCA.25 Angelini et al. proposed an approach to risk-stratify the more common anomalous right coronary artery arising from the opposite sinus of Valsalva, in which the degree of stenosis in the intramural segment is determined by the use of IVUS throughout the cardiac cycle.26 We have used cardiac catheterization with IVUS and FFR measurement with adenosine and/or dobutamine for risk stratification, and it has allowed us to identify significant decrease in the lumen and flow of coronary arteries with an intramyocardial segment in the setting of both AAOCA and myocardial bridges.25 Our initial experience has been published elsewhere.25 We have mainly used cardiac catheterization with IVUS/FFR in patients with long intramyocardial or intraseptal course of the coronaries and concerning symptoms or signs of ischemia and in patients with AAOCA and unclear anatomy. Due to the absence of guidelines regarding normal values in pediatric patients, we have used parameters similar to the ones used in adult patients with coronary artery disease (FFR < 0.8 after administration of adenosine and/or dobutamine). The validity of this threshold remains to be validated in AAOCA patients, but we have observed patients with abnormal FFR prior to surgical intervention return to normal values following surgery (unpublished data). Additionally, we have looked at the correlation between FFR and stress CMR and demonstrated good correlation between abnormal FFR measurements and perfusion abnormalities on stress CMR (manuscript in preparation).
CLINICAL DECISION MAKING AND MANAGEMENT
The optimal management strategy for patients with AAOCA remains controversial given the many uncertainties related to risk factors according to anatomic subtypes, the true risk for SCD over a lifetime, and the longitudinal effect of intervention versus nonintervention. Based on the many unknowns and the need for meaningful data, efforts have been made nationwide to develop programs to evaluate and manage these patients.2,27 Our team has developed a dedicated Coronary Anomalies Program (CAP) to evaluate and manage these patients more consistently using a standardized approach to diagnosis, management, and follow-up. A clinical algorithm for workup and management was developed based on the available data and consensus of a multidisciplinary team of pediatric and adult cardiologists, interventional cardiologists, surgeons, cardiovascular radiologists, cardiovascular anesthesiologists, nurses, and research and outcomes staff (Figure 5).
As part of the algorithm, patients with AAOCA who are referred to the CAP are evaluated by a core group of pediatric cardiologists and undergo standardized testing including electrocardiography, echocardiography, advanced imaging with retrospectively ECG-gated CTA, and myocardial functional studies, specifically EST and stress CMR. In a small number of patients, cardiac catheterization with IVUS and FFR is also indicated. The CAP team holds biweekly multidisciplinary meetings to review and discuss patients' data and decide on the best management. In general, patients with an anomalous left coronary artery and high-risk anatomy (origin from the opposite sinus with interarterial / intramural course) are offered surgical intervention. Patients with other coronary anomalies are offered surgical intervention if they have concerning characteristics such as symptoms clearly ascribed to ischemia, a positive functional test, or high-risk anatomy such as a long intramural course and ostial abnormalities, regardless of symptomatology. Patients undergoing surgical intervention are placed on low-dose aspirin on postoperative day 1 and continued for 3 months postoperatively. Troponin levels are not routinely trended in these patients.
In general, given the lower perceived risk of SCA in very young patients, we tend to defer surgical intervention in pediatric patients until they are older than 10 years of age unless they have evidence of ischemia. The threshold for surgical intervention is similarly higher for asymptomatic patients older than 35 years of age since they also seem to have a lower risk of SCA.
All patients are followed at particular time intervals. Patients who undergo surgical intervention are re-evaluated after 3 months with electrocardiography, functional testing, and CTA. If the workup is reassuring, patients are allowed to return to full exercise activities. In general, exercise restriction is only recommended for patients who are awaiting surgical intervention, who are currently in the postoperative period, who have high-risk lesions and refuse surgical intervention, or who have ischemic symptoms or positive functional testing but whose anatomy is unsuitable for surgical intervention. Patients with low-risk lesions that do not warrant surgical intervention are not exercise restricted.
Since the majority of SCD events occur during or immediately after intense exercise,1 exercise restriction has been recommended as a management strategy to prevent SCD in some patients with AAOCA.28 However, the effectiveness of this strategy is unclear due to reports of patients suffering from SCD while engaged in minimal activity.29 In addition, exercise restriction is not a benign strategy since it increases long-term cardiovascular risks and likely has a significantly negative psychosocial impact in young athletes.30 Based on a decision analysis by our group, we found that exercise restriction was not a preferred long-term strategy in any cohort of patients with AAOCA due to its detrimental long-term effect.31 We only recommend exercise restriction in patients awaiting surgical intervention and those who have clinical symptoms or ischemic findings during exercise.
SURGICAL TECHNIQUES AND OUTCOMES
Multiple surgical procedures have been performed in an attempt to treat ischemic symptoms or prevent SCD in patients with AAOCA. However, without a clear understanding of the pathophysiological mechanisms of SCD in AAOCA, it is difficult to define the optimal surgical strategy for a particular patient.
When an intramural coronary segment is present, we use the unroofing procedure (Figure 6), which removes the intramural segment by excising the intervening wall between the lumens of the aortic and anomalous coronary. The procedure also increases the size of the ostium and essentially moves it to the correct sinus (Figure 7 A). The longer the intramural segment, the more effective the procedure is at relocating the ostium. However, if the intramural segment is relatively short (< 5 mm, in our experience), the procedure may fail to relocate the ostium to the correct sinus and/or the anomalous vessel may be at risk of compression by the intercoronary pillar (Figure 7 B). Therefore, a short intramural segment may require a different procedure. Although some authors have used the unroofing procedure with commissure takedown and resuspension when the intramural segment travels below the level of the aortic valve, we advise against it because of the long-term risk of developing aortic valve incompetence.32
Coronary translocation entails dividing the coronary artery as it arises from the aortic wall and reimplanting it into the correct sinus. Some groups have advocated the universal use of this procedure because it closely resembles the normal coronary arrangement.33 However, the procedure is technically more demanding, and the long-term results of creating a circumferential anastomosis of the coronary artery on the aorta are unknown. As such, we reserve this procedure for cases in which the intramural segment travels below the level of the aortic valve or for patients with an absent or short intramural segment (Figure 7).
Creation of Neo-Ostium
This procedure is used for patients with a long intramural segment that travels below the level of the aortic valve. It entails unroofing the portion of the intramural segment that sits within the correct sinus while leaving the rest of the intramural segment (behind the aortic valve) alone.34 The intramural segment within the correct sinus has to be long enough to allow for an adequately sized neo-ostium.
Based on the premise that the presence of an interarterial segment between the aorta and the pulmonary artery may be a pathophysiological mechanism of SCD, some groups have advocated the use of a lateral or anterior pulmonary translocation for patients with a single coronary artery or those with no intramural segment.35,36 These procedures increase the available space between the aorta and the pulmonary artery.37
Several other procedures have been described to treat AAOCA, including coronary artery plasty,38 unflooring/unroofing procedure (ie, performing both an unroofing and a patch plasty),39 and coronary artery bypass grafting, although this is likely an ineffective procedure for most patients with AAOCA because of the very intermittent nature of ischemia and the consequent risk of thrombosis due to competitive flow. Other groups have suggested using ostial coronary artery stenting in the catheterization lab to prevent compression of the proximal segment of the anomalous coronary in adults.26 The long-term results of such a strategy, especially in young patients, is unknown.
Multiple retrospective and prospective surgical series have shown that surgical intervention for AAOCA can be performed with relatively low perioperative risk and good mid-term outcomes.40,41 However, there have been reports of patients suffering from cardiac events following surgical intervention for AAOCA.42,43 The cause of these events is unclear but may represent persistent compression of the coronary artery by a residual intramural segment or by the intercoronary pillar,43 the existence of an arrhythmogenic myocardium due to chronic ischemia, or other poorly understood mechanisms that translate into persistent risk of SCD.
Many questions still remain regarding the diagnosis and management of patients with AAOCA: Who is at risk of SCD? What is the actual risk? What is the optimal strategy for a particular patient? Only by developing strategies to standardize workup and follow-up of patients with AAOCA will we be able to better understand this disease and come closer to defining the optimal management strategy for individual patients. Initiatives such as the multi-institutional Congenital Heart Surgeons' Society AAOCA Registry,2 dedicated programs in academic institutions,3,27 and other multicenter collaborations will help advance our understanding of this disease.
In addition, all of the uncertainty can have a significant impact on the emotional and psychosocial wellbeing of patients and families with AAOCA, and this aspect has been poorly studied. It is incumbent upon us to develop protocols to study the psychosocial implications of this diagnosis and to design effective strategies to mitigate these concerns as we move the field forward.