Undiagnosed anomalous coronary arteries are a well-recognised cause of sudden cardiac death in children.Reference Maron, Shirani and Poliac1 Anomalous coronary patterns include origin of a coronary artery from the contralateral sinus and a single coronary artery. All patients with an anomalous left main coronary artery origin from the right sinus of Valsalva are generally referred for surgical repair, whereas operative decisions pertaining to patients with an anomalous right coronary artery origin remain controversial. Generally, patients with symptoms of ischaemia or arrhythmia with either form of the anomaly are referred for surgical repair, whereas asymptomatic patients with an anomalous right coronary artery pose a management dilemma. In addition, a review of the literature documents case reports of familial clustering, thus sparking the question of whether first-degree relatives should undergo screening.
Here, we provide clinical examples of familial clustering of congenital abnormalities of the coronary arteries. In discussing these patients, we hope to assess the risk of sudden death in patients with anomalous coronary arteries, the risk for first-degree relatives, the best screening modalities to establish diagnosis, and, if echocardiographic assessment of the coronary arteries is unclear, how far to pursue diagnosis.
Clinical cases
Patient T.M.
Patient T.M. was a 10-year-old African-American boy on multiple select level teams with no history of chest pain or other cardiac symptoms. He collapsed while actively playing basketball and was resuscitated on site for 45 minutes with ongoing resuscitation on arrival at the Johns Hopkins Hospital Pediatric Intensive Care Unit. He was emergently placed on extracorporeal membrane oxygenation and had a peak Troponin I of 440.6 ng/ml. His family history was significant for a maternal grandfather with a pacemaker and a paternal great uncle with adult-onset coronary artery disease requiring by-pass surgery. There was no history of sudden death.
In the Pediatric Intensive Care Unit, T.M. received a transthoracic echocardiogram that showed severe global left ventricular dysfunction. There was difficulty in fully delineating the coronary arteries, necessitating a transoesophageal echocardiogram, which showed anomalous origin of the left main coronary artery arising from the superior aspect of the right anterior facing coronary sinus. The proximal left main coronary artery had an intramural course, and there was a separate origin of the right coronary artery (Fig 1).
(a) A transoesophageal echocardiogram image demonstrating an anomalous left coronary artery (LCA) arising from the right coronary cusp with (b) colour flow Doppler imaging showing flow through the anomalous vessel.
On serial clinical examinations and an echocardiogram, there was no improvement in cardiac function. He underwent interventional catheterisation to vent the left atrium while on extracorporeal membrane oxygenation with no improvement in function and was thus subsequently listed for transplant. While on the transplant list, he received a repeat catheterisation with stent implantation to palliate a 70% long segment narrowing of the left main coronary artery. A left ventricular assist device was placed as a bridge to transplant, but he developed extensive subdural haematoma, midline shift, and herniation while on extracorporeal membrane oxygenation, and support was withdrawn. On autopsy, it was confirmed that he had anomalous origin of the left main coronary artery from the right sinus of Valsalva with a separate orifice compared with the right coronary artery. There was associated circumferential infarcted tissue involving 50% of the left ventricle.
Patient D.M.
His brother, patient D.M., is an 8-year-old African-American boy. Given the unexpected diagnosis and subsequent death of T.M., their parents requested screening of D.M. who had been evaluated at an outside hospital for a heart murmur. He was also healthy and active in sports. He had previously been at an outside hospital and was found to have a small atrial septal defect, although his coronaries were not formally evaluated. On arrival at Johns Hopkins Hospital, he was seen to have a benign physical exam and a normal electrocardiogram. A transthoracic echocardiogram confirmed the small atrial septal defect and showed normal cardiac function with a normal left coronary origin and course. However, there was concern for an anomalous right coronary artery origin with a separate orifice from the left coronary sinus. He subsequently underwent a cardiac CT, which confirmed the echocardiographic findings (Fig 2).
(a) A transoesophageal echocardiogram image demonstrating an anomalous right coronary artery (RCA) arising from the left coronary cusp, as well as flow through the vessel confirmed by (b) a cardiac CT three-dimensional reconstruction image demonstrating the anomalous RCA and the left main coronary artery arising from separate ostia at the left coronary cusp. As visualised here, the aberrant RCA courses between the aorta and the pulmonary artery. The left main coronary artery distributes normally.
The above findings were discussed with his parents, who opted for elective repair. In the operating room, he was found to have an anomalous right coronary artery with an intramural portion coursing between the right and left coronary sinuses. He underwent unroofing of the intramural portion of the right coronary artery, with myocardial revascularisation to the right coronary artery completed with the right internal mammary artery, and was discharged home on post-op day 4. The indications for surgical intervention were parental anxiety and the uncertain risk of adverse events, as well as the long intramural course of anomalous right coronary artery. On follow-up visits, his echocardiogram and stress testing showed widely patent right coronary artery, normal biventricular function, no aortic valve regurgitation, and normal exercise capacity with no ischaemia. He continues to play competitive basketball.
Additional cases
In addition to the aforementioned cases, there have been other case reports of familial clustering of coronary anomalies. Unpublished is the case of another sibling pair at Johns Hopkins Hospital, with one patient having the left main coronary artery arise from the right, while the brother had the right coronary artery from the left. Direct correspondence via personal communication shows similar families at other institutions.
In 2001, Bunce et alReference Bunce, Rahman and Keegan2 described three sisters with angina. One of the sisters had an anomalous right coronary artery originating from the left posterior sinus of Valsalva, whereas the other had an anomalous left coronary artery originating off the right coronary artery. In 2005, Laureti et alReference Laureti, Singh and Blankenship3 described two brothers with anomalous origin of the left coronary artery from the right sinus of Valsalva discovered by coronary angiography as part of the evaluation for stable angina. Neither patient had evidence of atherosclerotic coronary artery disease on angiography, with symptomatic chest pain in both cases, attributed to the anomalous left coronary artery. Finally in 2007, Horan et alReference Horan, Murtagh and McKeown4 described a patient with anomalous origin of the right coronary artery off the circumflex. On elective angiography, his daughter was found to have an anomalous left coronary artery arising from the right coronary artery.
Discussion
Risk of sudden death
Coronary artery abnormalities comprise 20% of cases with sudden cardiac death in young athletes, only second to cardiomyopathies, which comprise 35%.Reference Papadakis, Whyte and Sharma5 Studies on the incidence of anomalous coronal arteries vary in their findings on which anomaly is most common, but all describe the higher risk of sudden death in patients with an anomalous left coronary artery. Yamanaka and HobbsReference Yamanaka and Hobbs6 noted in 1990 that an anomalous origin with the right coronary artery arising from the left coronary sinus is far more common than the left coronary artery from the right sinus. They performed coronary arteriography on 126,595 patients over a 28-year period and showed that of the 13,686 (1.3%) patients who had coronary anomalies 136 (0.17%) had right coronary artery from the left coronary artery sinus, whereas 22 (0.047%) had the left coronary artery arising from the right coronary artery sinus. In a 25-year review in military recruits (6,300,000) from the Department of Defense Recruit Mortality Registry, Eckart et alReference Eckart, Scoville and Campbell7 found 126 non-traumatic deaths, of which 86% related to exercise. In 21 of these patients, the autopsy findings were that of a left coronary artery from the right coronary artery sinus. No patient had a right coronary artery from the left coronary sinus. However, in 2005, Mirchandani and PhoonReference Mirchandani and Phoon8 reviewed autopsy studies and showed that death attributed to anomalous coronaries was more common in anomalous origin of the left coronary artery (53%). There were a significant number of patients with an anomalous right coronary artery (24%). It is important to note that because these studies are essentially based on evaluation of autopsies the true prevalence is difficult to determine and only evaluates fatal cases versus near misses.
Best screening modalities
The transthoracic echo remains the gold standard, as the proximal left coronary artery and right coronary artery can be visualised in about 95% of young athletes.Reference Pelliccia, Maron, Spataro and Caselli9 However, in both of our cases mentioned above additional imaging was performed. For inconclusive cases, other modalities to consider include transoesophageal echocardiogram, CT, and/or MRI and magnetic resonance angiogram. Each of these modalities has challenges compared with a transthoracic echocardiogram. CT has excellent spatial resolution and can usually be performed without sedation or anaesthesia; however, there is concern for radiation exposure. The transoesophageal echocardiogram has both excellent spatial and temporal resolution but requires general anaesthesia in most children. Both the CT and transoesophageal echocardiogram can define the length of an intramural course. In MRI and magnetic resonance angiogram, the spatial resolution is inferior compared with a CT scan, although it is usually adequate to define the origin of the coronary arteries. MRI can assess the left ventricular myocardium and regional areas of decreased contractility; however, it requires sedation or anaesthesia in younger patients. CT and MRI and magnetic resonance angiogram can both show three-dimensional reconstruction of the coronary arteries, which can be especially useful when assessing the high origin of the anomalous coronary artery, as the ostium of the coronary artery is superior to the sinotubular junction. In considering these different options, additional consideration should also be given to the surgeon’s preference in planning the treatment. At our institution almost all patients scheduled for surgery undergo a CT scan with three-dimensional reconstruction.
Controversies in management
In the literature, the incidence of sudden death in the case of an anomalous left coronary artery is high; however, an anomalous right coronary artery is not a benign condition. Over the past 25 years, clinical case reports have described 10 asymptomatic patients who died suddenly with an anomalous right coronary artery arising from the left coronary artery sinus. None of these patients were younger than 10 years of age, nor were they adults older than 30 years of age. In consensus, all anomalous left coronary artery patients are referred for surgical repair, as well as patients with symptoms of ischaemia or arrhythmia with either form of the anomaly. As operative decisions regarding asymptomatic patients with an anomalous right coronary artery remain controversial, each patient is evaluated on the basis of a risk–benefit analysis.
Our practice
Currently at Johns Hopkins Hospital, patients with an anomalous left main coronary artery from the right sinus are referred for surgical repair regardless of symptoms. Patients with an anomalous right coronary artery from the left sinus of Valsalva, if they are symptomatic, are referred for surgical repair if feasible. If asymptomatic, they undergo serial follow-up visits with transthoracic and stress echocardiograms.
It is our policy to recommend screening with a transthoracic echocardiogram for all first-degree relatives of patients diagnosed with an anomalous coronary artery. The decision of whether to pursue other imaging if echocardiography is not conclusive requires individualized decision-making.
