The correct answer is: F. Either C or E may be considered.

Background

Anomalous coronary arteries are rare, but second to hypertrophic cardiomyopathy constitute an important cause of sudden cardiac death (SCD) in young athletes. The true prevalence of anomalous aortic origin of a coronary artery (AAOCA) is unknown, but is estimated to be between 0.1% and 1.0% in the pediatric and adult populations.¹ ARCA is approximately 4-6 times more common than ALCA, although the risk of SCD with ALCA is 4-5 times greater.² Surgery and competitive exercise restriction are recommended for ALCA regardless of symptoms, but the management of asymptomatic ARCA is much more controversial, as the risk with this variant is poorly defined. Data comes largely from autopsy studies, surgical registries, and imaging studies and some prospective registries, but has not offered proof that either surgical or conservative management prevents SCD.³

In Maron et al.'s analysis of sudden death in competitive athletes in the United States, ACA was the second leading cardiac cause of death in athletes with 17% (119/690) attributed to anomalous coronary arteries, although only 2.3% (16/690) of those were ARCA.⁴

Brothers et al. extrapolated this data to estimate a mortality risk of 0.2% for ARCA over the 20-year period of highest risk (ages 15-35 years).¹ This is quite low, and it raises the question as to whether prophylactic cardiac surgery in an asymptomatic individual with a small but non-zero risk is warranted. It is also known that exercise restriction can have its own adverse health and psychosocial consequences.

A number of anatomic features have been proposed to confer higher risk, including length of intramural course, acute angle take-off (<45 degrees), slit-like vessel origin and proximal vessel narrowing/hypoplasia (>50% luminal diameter). This is intuitive, since the proposed mechanism for ischemia and arrhythmias is dynamic compression that is increased during exercise, with greater compression during systole, increased aortic wall stress and a possible component of coronary spasm.⁶ In autopsy studies there has been evidence of chronic ischemic injury with patchy necrosis and fibrosis,⁶ and in other series, late gadolinium enhancement on MRI.⁷ Unfortunately, presence of certain anatomic features has not consistently correlated with either symptoms, positive functional testing or prognosis.^8-11 While several of these features have been associated with increased risk in small cohorts, it is still unknown how much weight to assign to each.^9,12

The majority of cardiac events related to coronary anomalies occur during or shortly after exercise.³ Symptoms may include typical angina, exertional syncope/presyncope or palpitations, although some patients have vague symptoms such as atypical chest pain at rest. Athletes may have competed for years at a high level of intensity prior to sudden onset of symptoms, and it is not well understood what triggers functional significance in one particular moment versus another.

Ischemic symptoms are hailed as a hallmark of physiologic significance and are thus an indication for treatment, although many patients have no symptoms prior to diagnosis. In the Congenital Heart Surgeons Society Registry, only 54% of 198 young patients reported symptoms prior to diagnosis.¹³ In the Texas Children's Hospital Coronary Artery Anomalies program, 51% of the 90 young athletes with ACA were asymptomatic.¹⁴ When the anomaly is discovered incidentally, particularly in younger patients, the lack of symptoms does not necessarily portend a benign prognosis. In a study of 27 young competitive athletes with SCD due to coronary anomalies, 63% had no prior symptoms.⁶

This alarming fact raises the question, how can we better screen for and diagnose these anomalies? With isolated ACA, the physical exam and EKG are normal, and the diagnosis requires dedicated imaging. Current athlete screening guidelines recommend comprehensive history and physical, with 12-lead EKG or echocardiography only in select populations.¹⁵ While echocardiography is an attractive option for screening to rule out ACA as well as other significant structural abnormalities such as HCM, widespread use in asymptomatic athletes is not recommended, in part due to cost, potential for false-positives and false-negatives, and the relatively low prevalence of life threatening cardiac disease in the general population.¹⁵ Echocardiography can visualize coronary origins in over 90% of athletes undergoing screening in research studies, and although this number may be lower in wider clinical practice, it remains the first line diagnostic test of choice for children and has the advantage of no radiation exposure.¹⁶ Coronary CTA and MRI (with invasive angiography in limited instances) are Class I recommendations for defining the course and anatomic features (Class I, LOE C-LD).³

When the diagnosis is made in an asymptomatic athlete, the critical question remains regarding clinical significance and risk of sudden cardiac death. In caring for these patients, the stakes of being 'wrong' can be very high. Unfortunately, due to the intermittent nature of ischemia with ACA, the negative predictive value of stress testing in this population is low and offers limited reassurance to both patient and provider. Basso et al. reported that in all six athletes with ACA that had testing prior to sudden cardiac arrest, all exercise tests were normal.⁶

The Eligibility and Disqualification guidelines recommend exercise stress testing, and the updated Adult Congenital Heart Disease (ACHD) Guidelines recommend 'physiologic evaluation,' although neither mandates a specific modality.^3,17 Exercise stress echo, nuclear perfusion imaging and stress CMR are more commonly used, with CMR having the advantage of also assessing for evidence of scar or fibrosis. Other modalities have been studied (hybrid coronary CTA/PET-MPI, coronary CTA/SPECT-MPI, invasive angiography with IVUS or FFR +/- dobutamine, OCT) and may provide adjunctive information, based on limited data.¹⁸ Often the choice of test may be influenced by institutional availability and expertise, as well as radiation, cost, small but real risks related to invasive procedures and patient factors such as age.

If possible, one may want to try to mimic the modality of exercise of an athlete by either using specific testing equipment or by modifying a protocol to include burst activity. Regardless of modality, provocation of ischemia is helpful when present as it is an indication for surgical intervention, but a negative test does not exclude potential for risk.

Management

As described above, surgery is recommended for ALCA without symptoms (Class IIa, LOE C-LD), and for ALCA or ARCA with symptoms or documented ischemia (Class I, LOE B-NR), but for asymptomatic ARCA, optimal management is less clear.³ If ventricular arrhythmias are provoked by testing, surgery is 'reasonable' (Class IIa, C-EO).³ If the patient remains asymptomatic and all testing is unrevealing, either surgery or continued observation is reasonable (both Class IIb, B-NR) in the absence of features 'suggesting potential for compromise of coronary perfusion' (e.g., intramural course, fish-mouth-shaped orifice, acute angle), but it is also recognized that current data does not prove that surgical interventions alter the risk of SCD.³

Surgical intervention for AAOCA, particularly interarterial or intramural lesions, is usually an unroofing procedure, which is done via anterior aortotomy, with an incision in the common wall between the aorta and the intramural segment of the coronary artery to eliminate compression and effectively relocate and enlarge the ostium.¹ If the anatomy is not amenable to unroofing, pulmonary artery translocation, coronary reimplantation/ostial reconstruction or bypass grafting may be used.¹ While most adult cardiologists are most familiar with bypass grafting, it has distinct disadvantages in this scenario which include competitive flow from only intermittent ischemia and has a limited role.

Surgical mortality is exceedingly low, although in a prospective study of 44 patients aged 8-18 undergoing surgery for AAOCA, there were perioperative complications in 20%, including repeat bypass run to control bleeding, need for CABG after technical complications related to complicated translocation, and pericardial effusions in 9%.¹⁹ PCI is not commonly used and there is limited data regarding safety and longevity.¹ In a retrospective study of ARCA patients with proximal intramural stenosis, Angelini et al. showed that cross-sectional area of the intramural segment was increased with stent angioplasty and improved symptoms, although the older age of the patient population (average age 48 years) and concerns about durability of revascularization limit the applicability of these findings to the young athletic population.³⁰ Regarding medical therapy, beta blockers have been studied, but at this time are not routinely recommended by expert consensus and are often poorly tolerated in athletes.¹

The rationale behind surgical correction is to alleviate the mechanism of ischemia, and while most patients are free of symptoms and can return to activity unrestricted, there is no evidence that surgery lowers risk of SCD. Some patients still have postoperative findings of ischemia on testing; Mery et al.'s prospective surgical study reported 14% with an abnormal sNPI post-surgery, three of which were new reversible defects in ARCA patients; all had normal CTAs and two had a normal stress CMR.¹⁹ The mechanism for or significance of these findings is unclear.

Competition and Exercise Recommendations

Current AHA/ACC Eligibility and Disqualification guidelines recommend that athletes with an anomalous right coronary artery with symptoms, inducible ischemia on exercise testing, or arrhythmias be restricted from all competitive sports (with the possible exception of class IA), prior to surgical repair (Class III, Level of Evidence C).¹⁷

Athletes post-surgical repair may be allowed to compete in all sports at least 3 months after testing if the patient is asymptomatic and exercise stress test is normal (Class IIb, C).¹⁷ If the athlete has an anomalous RCA and no symptoms with negative testing, competitive sports may be permitted after discussion of risks and benefits (Class IIa, C).¹⁷

While there are few data to support this recommendation, there are even fewer to inform recreational exercise practices. Expert consensus documents put forth some recommendations for surveillance in the non-restricted patient in terms of imaging and exercise testing (annual clinical evaluation with EKG, echo every 1-2 years, stress test every 1-3 years, Holter monitor as needed). AEDs should be available at team practices and competitions. Patients should be educated on symptoms, maintaining adequate hydration, and knowing when to stop exercising.¹

Given the intermittent nature of ischemia despite negative provocative testing, it also may be prudent to counsel the athlete regarding factors that may create additional physiologic stress or create the 'perfect storm' of conditions, such as avoiding exercise during significant illness or dehydration, using caution in extremes of temperature particularly high heat/humidity, avoiding vigorous unaccustomed exercise and abstaining from stimulants or performance enhancement aids other than electrolyte or nutrient replacement.³¹

Finally, age at incidental discovery has implications for prognosis. SCD due to AAOCA is very rare over the age of 35 or under the age of 10, although there is no age at which the risk is assuredly zero.^3,10 In a study of 66 patients with AAOCA with a mean age of 56+/-11 years there was no difference in MACE compared to age matched controls, regardless of anatomic variant (ALCA vs ARCA), intraarterial or intramural course, and 60-70% had at least one high risk anatomic feature.¹¹ There are at least two proposed explanations for these findings – one is potential increased stiffening of the vessel with age thus lessening degree of dynamic compression, and the second is survivor bias. SCD in athletes over age 35 is predominantly due to atherosclerotic coronary artery disease, and a study of middle-aged adults found ischemia found ischemia with AAOCA only when the vessel had concomitant obstructive coronary artery disease.²⁰

Conclusions

Care of asymptomatic athletes with incidentally discovered AAOCA is complex, and highlights the need for quality, prospective data to better inform risk stratification and management decisions. The decision to recommend prophylactic surgery, consider exercise restriction or observe is one that should be made after thorough assessment of the anatomic variant with imaging and provocative stress testing, taking into account patient factors such as age at presentation. The limited prognostic value of a negative functional test should also be acknowledged. The shared decision-making conversation with the athlete must include a thorough and frank discussion of the small but present unknown risk of SCD. When possible, multidisciplinary consultation should include experts in the field of coronary artery anomalies, including adult congenital specialists and cardiac surgery teams. Risks of proposed interventions must be weighed, as well as patient preferences, exercise goals, and the degree of value that the athlete places on exercise and competition. While there is often not one right answer, all of these things may help inform individual treatment decisions.

In this case, our athlete has high risk anatomic features, although may be at lower risk due to age at presentation and absence of symptoms (with a significant history of burst-activity competition) or objective ischemia on testing (which is of recognizably low negative predictive value). Per guidelines, either surgery or conservative management are Class IIb recommendations. After consultation with an adult congenital specialist and pediatric cardiac surgeon with a thorough discussion of risks and benefits, a strategy of conservative management without significant exercise restriction was mutually agreed upon. He was counselled, but not significantly restricted in his recreational activities. Patient preferences and exercise goals were taken into account, and while he enjoyed recreational running, he had no plans for vigorous competitive exercise. Guidelines for competitive sports participation would not mandate restriction without surgical correction, although it is important that the athlete fully understand and accept that a small but unquantifiable risk of SCD remains. Ongoing surveillance with repeat testing in 1-2 years is planned.

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