Prevalence of congenital coronary artery anomalies as shown by multi-slice computed tomography coronary angiography: a single-centre study from Turkey

Population

A total of 2401 consecutive patients (1805 men, 596 women; mean age, 56 ± 11.7 years; range, 15–88 years) who underwent electrocardiographically-gated 64-slice MSCT-CA from January 2005 to December 2008 were retrospectively reviewed for CAAs. Demographical data and the patients’ history were recorded. The presence of atherosclerotic coronary artery lesions was analysed using a dedicated workstation in a single institution (Maçka Emar, Istanbul, Turkey). The indications for MSCT-CA were atypical angina, typical angina with an inconclusive stress test, the presence of risk factors and high-risk patients for major coronary events, proximal stent patency at follow-up and bypass graft patency at follow-up.

Patients with unstable angina or acute coronary syndrome, atrial fibrillation, renal insufficiency (without the need for dialysis and a serum creatine level higher than 2.0 mg/dl), a history of contrast allergy and pregnant women were excluded. Verbal and written informed consent was obtained from all of the patients during their cardiovascular evaluation before MSCT-CA.

Imaging

Upon presentation to the CT scanner, patients with a heart rate > 70/beats/min received 50 mg atenolol per os (po) 40 min before the study, unless they had known overt heart failure, significant atrioventricular conduction abnormalities (second-degree atrioventricular block) or bronchospastic lung disease. Additional doses (up to a total of 15 mg metoprolol at 5 mg/min, 5 min apart) were administered if the target heart rate (< 65 beats/min) was not achieved and if systolic blood pressure was > 100 mmHg). In patients with major bronchospastic disease or with other contraindications to beta-blocker use, calcium channel blockers were used to control heart rate (intravenous diltiazem at a dose of 5 mg over 1 min repeated up to four times: total dose of 20 mg) every 5 min until the target heart rate was achieved and as long as systolic blood pressure was > 100 mmHg. All of the patients were scanned with a 64-slice CT scanner (GE LightSpeed VCT; GE® Healthcare). Angiographic scan parameters were as follows: number of slices per rotation was 64; individual detector slice width of 0.625 mm; and 12.5-cm spatial coverage in 5 s at a gantry rotation speed of 330 ms. After the patient was advanced into the scanner bore, the first acquisition consisted of a localizer image of the chest. The second acquisition was a non-contrast scan for calcium scoring. This second acquisition was performed with the following scanning parameters: gantry rotation time of 330 ms, tube voltage of 120 kVp, tube current of 225 mA, prospective gating at 70% of the R–R interval, and collimation of 64 ×0.625 mm. The third acquisition consisted of a test bolus scan, which was performed using a bolus of 20 cc of non-ionic iodinated contrast material (Optiray 350 [ioversol]; Mallinckrodt-Tyco Healthcare, USA). Segmental images were then obtained at 1 image/s over the aortic root. The scan was continued until a threshold of 100 Hounsfield units was reached in a region of interest positioned in the ascending aorta. This allowed graphical estimation of the timing needed for acquisition of the coronary angiogram. The final acquisition was a contrast-enhanced angiogram. Patients were asked to breathe deeply and then hold their breath at end-inspiration. Ioversol was administered according to the following protocol: 5 cc/s, according to the estimated prescan time (prescan time: timing bolus + 9 s [5 s breath hold time + 4 s for filling the distal coronary artery]), followed by a chaser bolus of normal saline (70 cc at a rate of 4 cc/s). The imaging parameters for this scan were as follows: rotation time of 330 ms, tube voltage of 12 0 kVp, and collimation of 64 × 0.625 mm. Image reconstruction was performed at 10% increments through the R–R cardiac cycle. After acquisition of images, images were transferred to a dedicated GE® AW Workstation for analysis.

CT image analysis

The CT data set was analysed by two independent experienced readers who were blinded to the patients’ clinical data. For analysis of the coronary arteries, the original axial dataset pre- (for calcium scoring) and post-contrast was examined. Volume rendering images and curved multi-planar reconstructions were also used for analysis. Types of abnormal coronary arteries were classified using the patients’ demographic data according to the American Heart Association scheme. ⁴ This scheme clearly describes the coronary artery map used by the Bypass Angioplasty Revascularization Investigation study for segmentation of coronary arteries, and was used to define and classify individual CAAs.^5,6 The types of abnormal coronary artery, including its origin, proximal course, intrinsic coronary anomalies and termination anomalies as seen by MSCT-CA, were collected.

Statistical analysis

Statistical analysis was performed using SPSS, version 15.0 (SPSS Inc., Chicago, IL, USA). Normality of distribution was evaluated with the Kolmogorov–Smirnov test. Normally distributed data are expressed as mean ± standard deviation and Q1–Q3 if data were not normally distributed. Results were analysed with the Student’s t test for quantitative data that were normally distributed and with the Mann–Whitney U-test for quantitative data that were not normally distributed. Categorical data were analysed with the chi-square or Fisher’s exact test (when Levene’s test was significant). P-values < 0.05 were considered statistically significant.

This study was approved by the No. 1 Clinical Research Ethics Committee of Istanbul at Istanbul University with no D-012 on November 10, 2009. The study conformed to the guiding principles of the Declaration of Helsinki.

Prevalence

The prevalence of CAA reported by MSCT-CA and by conventional CAG studies varies from 2.04% to 18.4% depending on the definition used and on the focus of the study.^7,8 Different results of the incidence of CAA from the literature are shown in Table 6. Unfortunately, most of the previous studies focussed on AOCs.^9–16 These studies did not use the same classification system to define CAA. Some groups included solely AOCs in their study population, while others included AOCs together with coronary termination anomalies (i.e., using a modified classification). ¹⁷ This difference in classification systems is the major cause of dissimilar incidences reported in these studies. The classification criteria for CAA have been widely discussed. Angelini et al. reported a classification that covers all possible coronary anatomical variations independently from their clinical and haemodynamic importance.^5,6 Altin et al.’s study compared the incidence of CAA in the same patient population. This incidence was calculated according to Angelini et al.’s classification and a modified classification, with two different frequencies of 1.4% and 2.7%, respectively. This finding indicates the importance of the classification system that is used for calculating the incidence of CAA.

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Table 6.

Incidence of CAA as shown by CAG and MSCT studies in various populations.

Authors	n	Coronary anomaly (n)	(%)
Incidence of coronary artery anomalies according to CAG studies
Eid et al. 8	4650	95	2.04 a
Yamanaka et al. 9	126595	1686	1.3 a
Tuncer et al. 10	70850	73	0.3 a
Aydınlar et al. 11	12059	100	0.8 a
Chaitman et al. 13	3750	31	0.8 a
Angelini et al. 31	1950	110	5.6
Topaz et al. 19	13010	80	0.6
Güntekin et al. 20	2398	55	2,3 b
Incidence of coronary artery anomalies according to MSCT studies
Cademartiri et al. 7	543	100	18.4
Srinavastan et al. 16	1495	11	0.8 a
Shi et al. 22	242	16	6.6 a
Ten Kate et al. 18	1000	10	1 a
Knickelbine et al. 37	4543	201	4.4 b
Zeina et al. 26	300	78	26 c

In the current study, the prevalence of coronary anomalies was 9.37% (225/2401), including all types of coronary anomalies with specified classification (as described by Angelini et al.). The current study showed that the incidence of AOCs was 1.5% (36/2401), which is in line with previous studies.^7,9,18 Reports from Turkey generally identify the incidence of AOCs by conventional CAG.^{10,11,17,19,20} Because conventional CAG is not the gold standard for the diagnosis of CAA, interpretation of these results is not accurate. To render different results comparable, investigators should use a strict classification system for coronary anomalies and include dedicated staff for analysis. The real prevalence of coronary anomalies is difficult to determine intrinsically because the techniques used for diagnosis are costly and time-consuming.

Among our population, 12 patients with AOCs had the RCA arising from the left anterior sinus of Valsalva. Eleven of the remaining 24 patients had the CX arising from the right anterior sinus of Valsalva (Table 2). Chaitman et al. ¹³ reported that the prevalence of AOCs was 0.83%. They also found that the RCA arising from the left anterior sinus of Valsalva was the most common type of anomaly with a prevalence of 70%. ¹³ Other studies have also postulated that the CX arising from the right anterior sinus of Valsalva or split origination of the left main coronary artery is the most common type of AOC.^8,9 Additionally, the RCA arising from the left anterior sinus of Valsalva has been reported as the most common type of AOC. ¹⁹ These studies included important data. However, because of the differences in the study populations, the techniques used, and their limitations, they are not eligible for comparison with the current study.

Clinical relevance

Although CAA is the second most common cause of exercise-related sudden death in athletes younger than 35 years, many patients with coronary anomalies are asymptomatic and are diagnosed at postmortem. ¹ Similarly, in the present study, patients with CAA and the subgroup including patients with coronary ectasia and a muscular bridge were less symptomatic compared with patients without coronary anomalies. Most patients with an anomalous origin of a coronary artery from the aorta are symptom-free.^14,21 A proposed mechanism of sudden death is believed to be episodic myocardial ischaemia. However, this mechanism cannot explain the clinical course because this hypothesis mainly proposes recurrent and rapid deterioration during exercise, but not the infarct size, as the responsible factor.

Shirani et al. ¹⁵ reported that sudden cardiac death cases with a single coronary artery were all free of signs of myocardial ischaemia or asymptomatic. Similarly, Datta and colleagues ¹⁴ reported that no patients with an anomalous coronary artery diagnosed by MSCT were symptomatic. These results could explain why coronary anomalies are generally diagnosed incidentally.

Demographic data

The aetiology of coronary anomalies is unknown and whether a hereditary background is involved has yet to be determined. In the current study, male sex was associated with CAA, which is in accordance with other studies that reported a male predominance (58%–80%).^{8,10,14,16,18,22,23,24} Similarly, Basso et al. reported that 80% of deaths caused by CAA in young athletes occur in male patients. ¹ The current study showed a frequency of 96.9% of male patients with aneurysmal coronary artery dilatation, similar to that reported by Swaye et al. (88.2%). ²⁵

Eid et al. ⁸ reported no association between atherosclerotic comorbidities, lipid profiles, and significant atherosclerotic lesions in patients with normal or anomalous coronary arteries. Other studies have also shown no association between anomalous coronary arteries, such as myocardial bridging,^26,27 coronary ectasia, ²⁸ and aneurysmal dilatation of the coronary arteries,^29,30 with coronary artery disease risk factors, such as diabetes, hypertension, hyperlipidaemia and smoking.

Increased risk of coronary atherosclerotic disease

Whether coronary anomalies predispose to early atherosclerosis or precede lethal influences is unknown. The current study showed a significantly higher incidence of coronary atherosclerotic changes and stenotic changes in anomalous versus normal coronary arteries. This finding has not been demonstrated by previous studies.^7,19 However, these results should be interpreted with caution because of their different haemodynamic and pathophysiological properties. Angelini et al. showed no association between the location of atherosclerotic coronary disease and anomalies of coronary anatomy/course. Many other studies have also reported similar results showing no association between AOC, such as single coronary artery and, an increased incidence of atherosclerosis.^5,8,13,19,31 In patients with a single coronary, if atherosclerosis occurs in the common trunk, the clinical consequences would be unusually severe because of the lack of collateral circulation. ³¹

However, the discussion is quite different for intrinsic coronary arterial anatomy abnormalities. Recent studies have focussed on the occurrence of atherosclerotic plaques in myocardial bridge localization. ³² They reported that the tunnelled segment was unusually affected by atherosclerosis, unlike the proximal epicardial segment, where atherosclerotic plaques were commonly found. There have been some reports on haemodynamic hypotheses on the association between a tunnelled coronary segment (intramyocardial segment) and ischaemia. ³³ However, the contribution of haemodynamic factors caused by a tunnelled segment on atheromatous plaque formation is still controversial. The current finding of a higher incidence of atherosclerotic changes and stenotic coronary lesions in this subgroup of patients with muscular bridges supports the hypothesis stating that the intramyocardial segment is an anatomical risk factor for coronary artery disease.^26,32

Coronary artery dilatations are usually associated with an underlying factor, which is atherosclerosis in Western countries and Kawasaki disease in Japan. ³⁴ The most common cause of coronary dilatation is thought to be atherosclerosis.^25,30,35 The current study supports the idea that coronary artery dilatation is an anomaly that develops based on atherosclerotic disease. Coronary artery ectasia is also associated with hyperlipidaemia, systemic hypertension, and male sex.^28,36

The current study has some limitations. Although the sample size in the current study is not small, this study was not able to determine the actual prevalence of CAA because the study group consisted of a relatively select group of patients (asymptomatic high-risk patients, asymptomatic patients with risk factors, high-risk patients for atherosclerotic lesions and symptomatic cardiac patients). Comparisons with other modalities, such as conventional CAG, or collecting long-term follow-up data are outside of the scope of this study.