Abstract
Background:
Anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) is a rare finding that is typically found on autopsy in a person with sudden cardiac death or during routine cardiovascular testing. The true prevalence is unknown for this reason. There is also question to the specific anatomy of the anomalies themselves and how best to correct them.
Methods:
We performed a retrospective chart review of all coronary computed tomography angiography (CCTA) studies to evaluate the incidence of all-cause mortality, nonfatal myocardial infarction, stroke and late revascularization (>90 days following CCTA) from January 2005 until July 2012. We describe the origin of the artery, its course, slit-like appearance and treatment in this population.
Results:
We reviewed 1518 CCTA reports and identified 22 patients with ACAOS with an incidence of 1.4% of our original study population over a review period of 6 years with a resultant median follow-up period of 25 months [interquartile range (IQR)25,75 12–34 months]. The indication for CCTA was for chest pain in the majority of patients (73%). We had one patient undergo surgical repair and one with coronary bypass grafting for unrelated symptomatic coronary artery disease.
Conclusion:
ACAOS continues to be a rare but presumed fatal condition in subsets identified to carry high risk features. As the characteristics of the anomalous vessels that increase risk are still debated, over an intermediate to long follow up in a single large center, none of the different anomalous findings with varying degrees of high risk findings were associated with sudden death.
Keywords
Background
Anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) with high risk features is a rare cause of sudden cardiac death (SCD), but one that is potentially treatable if discovered with early screening. The incidence of anomalous coronary arteries has been described previously to be 0.17–1% in groups referred for cardiovascular evaluation [Pelliccia, 2001; Angelini, 2007]. Angelini has previously reported an incidence of 5.64% in a referral population of 1950 patients undergoing invasive coronary angiography (ICA) [Angelini, 2007]. Yamanaka and Hobbs describe an incidence of 1.3% in a review of 126,595 patients who underwent ICA [Yamanaka and Hobbs, 1990].
Reviews have shown that ACAOS are found with increase incidences in both athletes (20%) and military recruits (33%) that present with SCD [Angelini, 2007; Eckart et al. 2004]. Eckart and colleagues reviewed the Department of Defense Recruit Mortality Registry from 1977 to 2001. This identified 126 nontraumatic, sudden deaths in a population of 6.3 million recruits. There were 21 deaths attributed to left coronary artery from the right sinus of Valsalva (L-ACAOS) [Eckart et al. 2004]. The mechanism of SCD in these populations is presumed to be arrhythmic in nature owing to myocardial ischemia due to the anatomy of the anomalous coronary artery (ACA) itself during exertion [Pelliccia, 2001; Angelini, 2007]. Angelini and colleagues have previously described that the likely culprit of ischemia in these patients is due to their intramural courses [Angelini, 2007; Angelini et al. 2006].
We performed a review of the rate of major adverse cardiovascular events (MACE) based upon the severity of coronary artery disease (CAD) in a single military center over a period of 6 years. This study excluded a small number of patients with incidentally discovered ACAOS [Lin et al. 2014]. In this review, we focused on the rate of MACE in the small sample of patients with ACAOS, evaluating both the severity of CAD as well as the characteristics of the coronary anomaly evaluated by coronary computed tomography angiography (CCTA) over a span of 6 years with reliable follow up based on Department of Defense electronic healthcare repository in conjunction with the Social Security Death Index (SSDI).
Methods
Patient selection
We performed a retrospective chart review of symptomatic adults at least 18 years of age who underwent 16-, 64- or 128-slice CCTA between January 2005 through July 2012 at a single center, tertiary referral hospital (San Antonio Military Medical Center, Joint Base San Antonio–Fort Sam Houston, Texas). The indication for the study for the great majority of our cohort was a chest pain syndrome, or evaluation for anomalous coronary anatomy as part of a syncope evaluation. Any segment that was deemed uninterpretable by the first reader was adjudicated by a level III imaging cardiologist. If the segment was unable to be read, then the study was deemed uninterpretable to decrease bias in results. Patients with history of myocardial infarction (MI) or stroke were also excluded. Subjects with renal dysfunction defined as a creatinine clearance <60 and positive human chorionic gonadotropin (HCG) testing were not studied in our analysis due to the inherent contraindication for undergoing CCTA. Institutional review board approval was obtained.
Noninvasive coronary artery analysis by CCTA
All scans were analyzed by a cardiologist with level III Society of Cardiovascular Computer Tomography (SCCT) experience. From January 2005 through December 2007, images were obtained using a 16 slice computerized tomography (CT) scanner (Brilliance-16®, Phillips, Amsterdam, Netherlands). Scans were performed in accordance with SCCT guidelines [Abbara et al. 2009]. From January 2008 to March 2011, images were obtained using a retrospective helical protocol with a 64 slice CT scanner (Somatom Definition CT®, Siemens, Erlagen, Germany). From March 2011 to March 2012, studies were obtained utilizing a prospective sequential protocol with a 60–80% image acquisition window. In March 2012, a 128 slice dual head scanner with a single heart beat image acquisition of the complete coronary when a heart rate of less than 60 was achieved (Somatom Definition Flash CT®, Siemens, Erlagen, Germany).
CCTA stenosis severity assessment
Initial analysis was performed by a level II imaging cardiologist, and adjudicated by a level III imaging cardiologist as per the method, where the severity of the disease was determined on a per patient and per vessel basis using the SCCT 18 segment model in accordance with SCCT guidelines for interpretation [Raff et al. 2009]. The major epicardial coronary arteries (left main, left anterior descending, left circumflex and right coronary) were visually analyzed for their origins and courses.
Follow up
The primary endpoint was composite MACE, defined as all-cause mortality, stroke, non-fatal MI and late revascularization (defined as revascularization performed at least 90 days after CCTA). We also compared the incidence of each MACE outcome individually based upon the severity of CAD. International Classification of Diseases (ICD) 9 codes for all-cause mortality (798.1, 798.2, 798.9 and V12.53), stroke (434.00, 434.01, 434.10, 434.11, 434.90, 434.91, 997.02 and V12.54), non-fatal MI (410.0–410.9) and late revascularization with percutaneous coronary intervention (PCI) (92980, 92981, 92982, 92995 and 92996) or CABG (33510-33514, 33516 and 33533–33536) were used for initial data extraction followed by Department of Defense outpatient and inpatient electronic medical record (EMR) verification of events. We determined mortality using the SSDI followed by reverification using EMR for last visit date as well as Tricare healthcare informatics division verification. All events identified by ICD-9 code were adjudicated.
Results
Clinical and CCTA characteristics of the study cohort
Of the 1519 CCTA studies included in our original study, 22 subjects with coronary anomalies were identified. Of the 22 subjects identified, the average age was 54 ± 16.2 years and 77% male predominance with no loss to follow up in EMR. Hypertension was present in 27% of the patients with 14% having hyperlipidemia. There was only one diabetic in the anomalous group, reflecting the low incidence found in the parent study (Table 1). Obstructive CAD was present in two patients in the anomalous cohort.
Baseline characteristics of the overall study group and the anomalous subgroup.
Values are % (n) or mean ± standard deviation.
Severity of coronary heart disease (CAD) was classified as obstructive (>50% stenosis), non-obstructive (<50% stenosis)., and no CAD (no angiographic disease).
ACA association with MACE
Over a median follow-up period of 25 months [interquartile (IQR) range 12–34 months] there was one patient with a MACE event. That event was a late revascularization. There were no reported incidents of mortality, stroke or non-fatal MI events in the anomalous cohort. The late revascularization was in a patient with an anomalous right coronary artery (RCA) and was for multivessel coronary disease. The RCA was bypassed for a distal stenosis.
ACA morphology
There were 22 patients with anomalous coronary origins in our cohort. Anomalous origins were described for each major epicardial vessel [RCA, left anterior descending (LAD), left circumflex (LCx)] independently. Of those 64% had an anomalous RCA origin, 14% had an anomalous LAD and 32% had an anomalous LCx. There was one patient with an anomalous left main coronary artery (LMCA) and one with both anomalous LAD and LCx arteries arising from the RCA. There were 12 interarterial coursing coronary arteries that were all anomalous RCA of the left coronary cusp. Slit-like orifices were present in 16 patients with 62.5% arising from the RCA (Table 2).
Anomalous coronary artery morphology by major epicardial vessel.
RCA–LCC, right coronary of left coronary cusp; LAD–RCC, left anterior descending of right coronary cusp; LCx–RCC, left circumflex of right coronary cusp.
Discussion
ACAOS is a rare but not an infrequent finding in referral populations that undergo invasive and noninvasive cardiovascular testing. They are associated with SCD, especially in the young, but the significance of the asymptomatic population with these anomalies has yet to be determined. We had an incidence of anomalous coronary arteries of 1.4% from our study group. This is slightly higher than the reported rate of 0.17–1% in the population. However, it is similar to other groups who have performed similar retrospective studies [Pelliccia, 2001; Angelini, 2007].
We compared the anomalous population to the entire cohort from which it was derived. The anomalous population was slightly older and there were a higher proportion of men in the group. Both hypertension and hyperlipidemia were lower in the anomalous group with a similar prevalence of diabetes mellitus. With regard to MACE, the annualized incidence in the anomalous group compared with 1.5% in patients without an anomaly (p = 0.7). This is limited due to the small number in the anomalous cohort.
Our original study showed the association of obstructive CAD on CCTA and the incidence of MACE to include stroke. The prevalence of obstructive coronary disease was similar in the population without anomalies (10%) and those with coronary anomalies (9%). Again our sample size for the anomalous group is too small to make any significant statistical comparison. There was one MACE event for late revascularization in the anomalous group who was found initially to have non-obstructive CAD on his CCTA. Thus, none of our patients at a median follow up of 25 months had a MACE event related to their coronary anomaly.
We were able to identify 22 patients in our study with ACAs and accurately describe their morphology with regards to origin and course of the arteries. The majority of anomalies were off an anomalous RCA off of the left coronary cusp (64%). The majority of these had an interarterial route (85%) after its origin from the left cusp. There was only one patient with an anomalous LMCA off the right cusp. A slit-like orifice was found in the majority of the patients with coronary anomalies (73%). These have traditionally been thought to be high risk findings in patients with coronary anomalies. However, Angelini suggests that it is not just these factors but rather the characteristics of the intramural segments that lead to risk. Specifically he discusses three features of intramural segments that determine severity: hypoplasia; baseline lateral compression; and further lateral compression as the patient ages [Angelini, 2006].
The main indication for CCTA that identified the coronary anomaly was a chest pain syndrome (73%). Of those that presented with chest pain there was no invasive treatment of the coronary anomaly. One patient in this cohort, who initially presented with fatigue, underwent surgical correction in a congenital center upon representation with similar symptoms. The indication for treatment (noninvasive and invasive: surgical versus primary coronary intervention) is still a source of debate. Surgical management for symptomatic patients is the traditional approach for symptomatic individuals [Peñalver et al. 2012]. However, PCI has shown some favorable results. There is concern, however, of long-term outcomes given the generally young age and large territories at risk [Angelini, 2006]. This approach may be more feasible in our population given the older median age of our population in this study.
Conclusion
ACAOS continues to have low prevalence in the general population with some subsets presumed fatal based on autopsy reports or symptomatic population with a component of referral bias. As the characteristics of the anomalous vessels that increase risk are still debated, over an intermediate to long follow up in a single large center, none of the different anomalous findings with varying degrees of high risk findings were associated with sudden death.
Footnotes
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest statement
The authors declare no conflicts of interest in preparing this article.
Disclaimer
The opinions in this manuscript do not constitute endorsement by San Antonio Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army, Department of Defense or the US Government of the information contained therein.