Anomalous Aortic Origin of a Coronary Artery: Symptoms Do Not Correlate With Intramural Length or Ostial Diameter

Abstract

Background:

Anomalous aortic origin of a coronary artery (AAOCA) is a known cause of sudden death. Our hypothesis was that longer intramural length and smaller ostial diameter correlate with preoperative symptoms. If true, this would assist in the decision for surgical indications. We also assessed the accuracy of preoperative imaging to predict intramural length.

Methods:

Retrospective analysis of patients who underwent AAOCA unroofing from 2006 to 2014. Patients had preoperative computed tomography angiography (CTA) or magnetic resonance imaging (MRI). Intramural length was measured. Intramural lengths and ostial diameters were also measured intraoperatively (operating room [OR]). Symptoms were noted. Intramural lengths and ostial diameters were compared between patients with and without preoperative symptoms. The accuracy of intramural length measured by CTA/MRI versus the length measured in the OR was assessed using a Bland-Altman analysis.

Results:

Sixty-six patients underwent surgical repair of AAOCA. Fifty-two (79%) patients were symptomatic and 14 (21%) were asymptomatic. Mean age was 12.4 ± 4.0 years. There was no mortality. There was strong agreement between intramural length measured by CTA/MRI and measured in the OR. There was no significant difference in AAOCA intramural length in the symptomatic (8.6 ± 3.5 mm) and asymptomatic (8.9 ± 2.8 mm, P = .77) patients, which were measured both by CTA/MRI and intraoperatively (symptomatic 7.3 ± 2.5 mm, asymptomatic 6.9 ± 2.8 mm; P = .62). There was also no significant difference in AAOCA ostial diameters between groups (symptomatic = 1.9 ± 0.5 mm, asymptomatic = 1.6 ± 0.5 mm; P = .09).

Conclusion:

Preoperative CTA/MRI was very accurate in predicting the length of surgical unroofing. There was no demonstrable correlation between preoperative symptoms and intramural AAOCA length or AAOCA ostial diameter.

Keywords

congenital heart disease coronary artery pediatric surgery cardiopulmonary bypass

Introduction

Anomalous aortic origin of a coronary artery (AAOCA) from the contralateral aortic sinus of Valsalva with an intramural course through the aortic wall is a rare congenital anomaly. Sudden death is the most devastating complication usually occurring in older children and young adults.^1,2 An analysis of over 125,000 cardiac catheterizations revealed 0.17% right AAOCA and 0.047% left AAOCA.³ Some of these patients have symptoms leading to a diagnosis such as angina, syncope, or dyspnea on exertion.^4,5 In some patients, sudden death is the first “symptom.”^6,7 Increasingly common, however, are patients presenting with vague symptoms in whom noninvasive imaging reveals the diagnosis. Surgical intervention is considered in these patients because of the fear of sudden death.^8,9 Surgical unroofing has emerged as the current surgical procedure of choice, although other techniques may be appropriate in select cases.^10,11

In 2011, we reported a possible correlation of symptoms with intramural coronary length in this patient population.¹² Because approximately half of all patients with sudden cardiac death have prior symptoms,^13
–15 if intramural length can be shown to correlate with symptoms, it would assist in the decision tree for surgery. In our conclusion, however, we cautioned, “that larger numbers of patients are needed to further validate these results.” The purpose of the current study was to utilize a larger cohort of patients to retrospectively evaluate a possible correlation between preoperative symptoms with the intramural length of the anomalous coronary artery. In addition, we assessed the ostial diameter of the anomalous coronary artery at the time of repair and attempted to correlate this finding with symptoms. Finally, we wanted to assess the accuracy of preoperative advanced medical imaging (computed tomography angiography [CTA]/magnetic resonance imaging [MRI]) to predict the measured operating room (OR) length of the unroofed segment.

Materials and Methods

Approval for the study was obtained from the Institutional Review Board of Ann & Robert H. Lurie Children’s Hospital of Chicago. The need for informed consent was waived. A retrospective analysis of the congenital cardiac surgery database was used to identify all patients who underwent surgery for AAOCA from 2006 to 2014. Information regarding patient demographics, symptoms, imaging features, operative details, and postoperative course (including length of stay, complications, and troponin levels) were obtained from a review of electronic medical records. In particular, symptoms such as chest pain, syncope, dizziness, palpitations, shortness of breath, exercise intolerance, and left arm pain were noted. We stratified “chest pain” into two categories, “anginal chest pain” and “atypical chest pain.” Anginal chest pain was defined as reproducible substernal discomfort or left arm/jaw pain brought on by exertion.

Imaging Protocol

Between 2006 and 2011, all patients referred for coronary imaging underwent CTA on a 64-slice single-source CT scanner (SOMATOM Sensation 64; Siemens Healthcare USA, Malvern, Pennsylvania). Between 2011 and 2014, patients who were referred with a high suspicion for an anomalous coronary artery for a preoperative study underwent CTA imaging on either a 64-slice single-source CT scanner (2011-2012: SOMATOM Sensation 64; Siemens Healthcare USA) or a dual source CT scanner (2012-2014: SOMATOM Definition Flash; Siemens Healthcare USA). Patients who were referred with a lower suspicion of an anomalous coronary artery usually due to poor echocardiography windows underwent MRI on either a Siemens 1.5 T Avanto (2011-2012) or a 1.5 T Aera (2012-2014; Siemens Healthcare USA). The intramural length of the AAOCA on the preoperative CTA or MRI was measured on a reconstructed image directly axial to the aortic root from the point of origin of the AAOCA to its point of exit from the aortic wall by a blinded pediatric cardiovascular radiologist (Figure 1) on a dedicated postprocessing workstation (Siemens MMWP; Siemens Healthcare USA). If the patient had measurements of both MRI and CTA, we used the CTA measurements.

Surgical Technique

All patients underwent median sternotomy and aortobicaval cardiopulmonary bypass with mild hypothermia and initial antegrade cardioplegic arrest. The senior surgeon in the group (C.L.B.) participated in all cases. From 2006 to 2011, subsequent cardioplegia doses were delivered retrograde. Since 2012, a single antegrade dose of del Nido cardioplegia has been used.¹⁶ In the first part of the series, the ascending aorta was transected to provide exposure. In the most recent 40 patients, the proximal ascending aorta was opened initially above the sinotubular junction and was then extended down into the noncoronary sinus in a “hockey stick” fashion. The ostium of the anomalous coronary artery was probed with a coronary dilator. The largest dilator diameter admitted was noted which gave us the ostial diameter pre-unroofing (Figure 2). With the coronary dilator inside the AAOCA, surgical unroofing was performed with a #15 blade along the intramural length up to the point where the coronary artery exited the aortic wall. Partial excision of the intima and media edges along the length of the unroofing was performed. Next the intimal edges were tacked to the media with a series of interrupted 7-0 or 8-0 prolene (Ethicon, Somerville, New Jersey) sutures. In five patients, a neo-ostium was created along the intramural course just proximal to the exit of the coronary artery from the aorta. In two patients, a side-to-side anastomosis was created. In one patient, the aortic valve commissure was partially detached and then resuspended to the aortic wall. The intraoperative intramural unroofed length was measured with a ruler (Figure 3). The unroofed coronary artery was again probed, and the diameter of the largest probe admitted was noted. We did not perform reimplantation or pulmonary artery translocation in any patient. We did not encounter any patients with extramural but interarterial course of the AAOCA.

Statistical Analysis

A two-tailed, paired Student’s t test was used to compare the mean intramural lengths as measured by CTA/MRI and directly measured in the OR in patients who had symptoms versus those who did not have symptoms. Bland-Altman plots were used to assess agreement between the intramural length as measured by CTA/MRI versus actual length of the unroofing in the OR. Bland-Altman plots are commonly used to assess agreement between the two measurement techniques, including the evaluation of systematic differences between two clinical measurements (systematic bias), an assessment of agreement between two measurements over the range of data (proportional bias), and identification of outliers.¹⁷ Systematic bias was assessed using a one-sample t test. A P value less than .05 was considered statistically significant.

Results

Sixty-six patients underwent surgical intervention for AAOCA. The mean age was 12 ± 4 years. The gender distribution was 41 (62%) male and 25 (38%) female. The right coronary artery originated from the left aortic sinus of Valsalva in 55 (83%) patients and the left coronary artery originated from the right aortic sinus of Valsalva in 11 (17%) patients. All patients had an intramural course through the aortic wall. None of the patients had a single coronary artery. All 66 patients underwent preoperative imaging with CTA scan (n = 49) or MRI (n = 22) or both (n = 5). In patients who had both imaging studies, we used the CTA images for this analysis.

Fifty-two (79%) patients were symptomatic; the distribution of symptoms is shown in Tables 1 and 2. Fourteen (21%) patients were asymptomatic. Of the patients with right AAOCA, 42 (76%) of 55 were symptomatic. Of the patients with left AAOCA, 10 (91%) of 11 were symptomatic. There was no early or late mortality. The mean hospital length of stay was 4.5 ± 1.0 days. There were two notable complications. One patient developed a pericardial effusion and underwent a pericardiocentesis four months postoperatively. A second patient developed pericardial effusion, heart block, and syncope on postoperative day 11, which led to emergent cardiac catheterization (coronary appeared patent) and operative re-exploration (coronary orifice confirmed open). The working diagnosis was a thrombus to the right coronary artery causing temporary right ventricular ischemia. The patient was uneventfully discharged seven days post re-exploration with no long-term sequela. Both of these patients had right AAOCA and both had preoperative symptoms of palpitations and an abnormal Holter monitor.

Table 1.

Incidence of Various Symptoms in Patients With Anomalous Aortic Origin of a Coronary Artery.^a

Symptoms	AAOCA (Right) n = 55	AAOCA (Left) n = 11
Anginal chest pain	14 (25%)	4 (36%)
Chest pain, other	12 (22%)	3 (27%)
Syncope	6 (11%)	0 (0)
Dizziness with exertion	1 (1%)	1 (9%)
Palpitations/arrhythmias	2 (3%)	0 (0)
Shortness of breath	0 (0)	1 (9%)
No symptoms reported	20 (36%)	2 (18%)

Abbreviation: AAOCA, anomalous aortic origin of a coronary artery.

^aNote that some patients have more than one symptom.

Table 2.

Subanalysis of Chest Pain, Other.

AAOCA, Right (n = 12)	# Patients	AAOCA, Left (n = 3)	# Patients
No other descriptor	5	No other descriptor	0
“Atypical”	1	“Atypical”	1
With dizziness	2	With dizziness	1
With dizziness and shortness of breath	1	With dizziness and palpitations	1
With dizziness and syncope	1
With syncope	1
With palpitations	1

Abbreviation: AAOCA, anomalous aortic origin of a coronary artery.

Results of the CTA/MRI and intraoperative measurements are shown in Table 3. For intramural length, agreement between preoperative CTA/MRI and intraoperative measurements was assessed using Bland-Altman analysis. Of the 66 study patients, 36 were excluded from the Bland-Altman analysis either because intramural length was not measured in the OR (early in our experience), or the CTA/MRI imaging was obtained at an outside institution which precluded retrospective measurements. For the remaining 30 patients, there was good agreement between the intramural lengths as measured by CTA/MRI versus actual length of the unroofing in the OR (Figure 4). The Bland-Altman analysis did not reveal evidence for significant systematic (P = .07) or proportional bias (95% confidence limits for regression line always include zero bias line), and only 2 (7%) of 30 patients were outliers.

Table 3.

Results: Anatomic Findings.

RCA from left sinus	55
LCA from right sinus	11
Intramural length measured by CTA/MRI scan	Mean length: 8.7 ± 3.3 mm, range: 1.5-17 mm
Intramural length measured in OR	Mean length: 7.3 ± 2.5 mm, range: 1.5-13 mm
Orifice size measured in OR	Mean: 1.8 ± 0.5 mm, range: 1.0-2.5 mm
Orifice size post unroofing	Mean: 2.8 ± 0.5 mm, range: 2.0-3.5 mm

Abbreviations: CTA, computed tomography angiography; LCA, left coronary artery; MRI, magnetic resonance imaging; OR, operating room; RCA, right coronary artery.

The mean intramural length as assessed by CTA/MRI in patients who were symptomatic was 8.6 ± 3.5 mm and in patients who were asymptomatic was 8.9 ± 2.8 mm (Figure 5). There was no significant difference in the mean intramural lengths comparing the two groups (P = .77). Evaluating the symptoms individually, no significant associations were found when comparing symptomatic versus asymptomatic patients. Similarly there was no significant difference in the mean intramural lengths as directly measured in the OR after unroofing between the two groups (symptomatic = 7.3 ± 2.5 mm, asymptomatic = 6.9 ± 2.8 mm; P = .62; Figure 6). There was also no significant difference in the mean intraoperatively measured AAOCA ostial diameter between the two groups (symptomatic = 1.9 ± 0.5; asymptomatic = 1.6 ± 0.5; P = .09; Figure 7). We measured baseline postoperative troponin levels in all patients for trending should the patient have signs of new myocardial ischemia later in the postoperative period. The mean troponin level at baseline (2-4 hours postoperatively) was 8.8 ± 7.1 nanograms/mL (minimum, 2.3; maximum, 45.8). The length of follow-up since operative repair was a median of 5.6 years and a mean of 5.7 ± 2.2 years.

Discussion

Decision-making for the patient with an AAOCA is quite complex. We know there are patients who present with sudden death as their very first symptom.^6,7 However, approximately 50% of patients who have sudden death have prior symptoms.^13
–15 There are also patients who present with no symptoms but have this anomaly found as an incidental finding during an evaluation for a completely unrelated condition. The question of who has indications to undergo operative intervention and who can be safely observed has not been fully answered. We previously reported on a small set of patients in which the presence of preoperative symptoms appeared to correlate with the length of the intramural coronary artery.¹² However, when reporting these findings, we cautioned that “larger numbers of patients were needed to further validate these results.”

In our current analysis with three times the number of patients, we were unable to confirm our prior findings. We found no significant association between preoperative symptoms and the intramural length of the coronary artery, and there was no significant association between symptoms and the coronary orifice size. We had previously thought that intramural length would help risk stratify these patients. This does not appear to be the case. Our results confirm the need for multiinstitutional studies reporting these patients in a systematic fashion to a registry with as much data as possible for each patient. The Congenital Heart Surgeons’ Society has organized such a registry.¹⁸

In evaluating coronary morphology to risk stratify patients for surgical intervention, CTA appears more useful than echocardiogram.¹⁹ Krupiński and colleagues reviewed CTAs in 54 patients with AAOCA. They noted that there were “high-risk” anatomic features such as a slit-like orifice and intramural course in patients with chest pain and cardiac events.²⁰ Ashrafpoor and coworkers looked at CTAs in patients who had major adverse cardiac events (MACEs).²¹ All patients with MACEs had minimum lumen area ≤4 mm, an area of stenosis ≥50%, or an intra-arterial length >10 mm. Biko and colleagues concluded that MR angiography may be able to reliably identify the intra-arterial segment of an anomalous coronary artery.²² In our series, the majority (81%) of patients had CTA evaluation. We agree with Lee and colleagues that CT is superior to MRI at the current time to assess accurate intramural length.²³

The results of surgical intervention as reported by several major institutions are quite good^{10,24

–30} (Table 4). In a collected series of over 450 patients, there was no reported mortality. However, there are reports of death and myocardial dysfunction after surgical repair. Nguyen and colleagues reported a 15-year-old who presented with syncope and had anomalous origin of the left coronary artery.³¹ Sudden cardiac death occurred shortly after resuming physical activity after surgical correction. Brothers and associates have reported subclinical ischemic changes in nearly 40% of 24 patients with repaired AAOCA.³² Brothers et al also reported some interesting findings in a survey sent to members of the Congenital Heart Surgeons’ Society.³³ Among patients known to have been managed medically, there were six sudden deaths. There were also two postoperative deaths reported in those who had surgical repair.

Table 4.

Patient Characteristics and Outcomes After Surgical Intervention for AAOCA.

Authors	Institution	Year Published	# Patients	Right From Left	Left From Right	Mortality	Asymptomatic
Turner et al²⁴	Duke	2011	53	40	13	0	20
Frommelt et al²⁵	CHOW	2011	27	20	7	0	12
Mumtaz et al²⁶	Cleveland	2011	22	15	7	0	1
Poynter et al²⁷	CHSS	2014	113	78	33	?	?
Mainwaring et al²⁸	Stanford	2014	76	47	27	0	25
Wittlieb-Weber et al²⁹	CHOP	2014	24	16	8	0	11
Sharma et al³⁰	Mayo	2014	75	69	6	0	20
Feins et al¹⁰	MGH	2016	30	24	6	0	?
Balasubramanya et al^a	Lurie	2016	66	55	11	0	14
Total			486	364 (75%)	118 (25%)	0	103 (23%)

Note: The “?” indicates that the number of asymptomatic patients in those studies were not indicated.

Abbreviation: AAOCA, anomalous aortic origin of a coronary artery; CHOP, Children’s Hospital of Philadelphia; CHOW, Children’s Hospital of Wisconsin; CHSS, Congenital Heart Surgeons’ Society; MGH, Massachusetts General Hospital.

^aCurrent study.

There is a wide variation in recommendations in the literature for AAOCA patients. Mainwaring and colleagues concluded, “it is our current recommendation that all teenagers identified with AAOCA should undergo surgical repair.”^28(p20) In contrast, Feins and colleagues concluded that only a small subset of these patients require an operation.¹⁰ The question of whether to offer surgical intervention to these patients varies widely from center to center.^34,35 When these patients are referred to surgeons, they have often been exercise restricted by their cardiologist. This leads to a “push” toward surgical intervention. Most clinicians appear to agree upon operative repair for patients with anomalous aortic origin of the left coronary artery.^10,26,30,36 There is also some agreement that patients with an anomalous origin of the right coronary artery with symptoms should undergo an operation.^10,28,30,36 The most difficult patient to stratify is the one with an incidentally noted anomalous right coronary artery with no symptoms or with symptoms not concerning for myocardial ischemia or exercise-induced arrhythmia. Our hope for these patients is that morphologic characteristics as defined by CTA/MRI may yield a more definite stratification. Our current investigative focus is on more detailed anatomic features of the anomalous coronary available on CTA, such as orifice type and endoluminal measurements.

Limitations

An inherent limitation of our analysis is that the focused study group is based on patients who were referred for operative repair. This of course excludes patients who may have been diagnosed but not referred for surgical intervention. However, we certainly do have a group of patients who were referred for surgical intervention who were not symptomatic and it is possible to compare those patients to the patients who presented with true coronary symptoms. Another possible limitation is that the measured values (CTA/MRI) were not normalized to body surface areas. This is balanced by the fact that the great majority of our patients were nearly fully grown. The standard deviation for the mean age was relatively tight at 12 ± 4 years. Another limitation is that there is no known direct correlation between symptoms and sudden cardiac death. However, there seems to be a general understanding in the literature that approximately 50% of patients who have sudden cardiac death have prior symptoms. Hence, there is some relevance as to whether a patient has symptoms and the recommendations for surgical intervention.

Conclusions

Our hypothesis that the intramural coronary artery length and/or ostial diameter would correlate with symptoms in patients with anomalous aortic origin of the coronary artery has been proven not to be accurate. These measurements do not appear predictive of symptoms and should be appropriately considered when risk stratifying patients for possible surgical intervention. In particular, we believe that a short intramural course does not necessarily protect a patient from sudden cardiac death. Our study does demonstrate that coronary unroofing appears to be a safe procedure for these patients. We also demonstrated that CTA and MRI accurately predict the intramural length as assessed directly in the OR. We agree with ongoing efforts to include patients in the multicenter registry sponsored by the Congenital Heart Surgeons’ Society to facilitate the development of evidence-based treatment and management guidelines for children and young adults with AAOCA.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Abbreviations and Acronyms

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