Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus is Associated with Early Development of Coronary Arte

Anomalous right coronary artery (AnRCA) from the left coronary sinus is found in only about 0.03–0.9% of patients undergoing coronary angiography.1,2 The AnRCA ostium originates either from within the left coronary sinus (Figure 1) or from the left aortic wall above the left coronary sinus (Figure 2). In either type, it is characterized by a course between the aorta posteriorly and the pulmonary trunk anteriorly (Figure 3) and is compressed by these structures. AnRCA is associated with sudden cardiac death during or after exercise, particularly in young athletes.3–7 Whether it also predisposes to early development of coronary artery disease (CAD) is still controversial. Methods From January 2000 to December 2002, a total of 1,532 patients were admitted for the first time to our unit for cardiac catheterization. All patients presented with chest pain; cardiac catheterization was subsequently performed to detect any underlying CAD. The coronary angiogram was retrospectively reviewed for the presence and characteristics of AnRCA as well as the presence and distribution of coronary atherosclerosis. According to the American Heart Association/American College of Cardiology guidelines, CAD is defined as >= 50% diameter stenosis in at least 1 of the major coronary arteries. The demographic data and the risk factor profiles of the corresponding patients were retrieved from the clinical records. Data were presented as mean values ± 1 standard deviation, counts or percentages. Differences between the groups with respect to continuous variables were compared with the two-sided t-test. Two-sided Chi-square or Fisher’s exact tests (whenever an expected cell value was Population. Among the 1,532 patients reviewed during the study period, thirteen had AnRCA (0.8%). The remainder (1,519 patients) had normal RCA origin. CAD was found in 804/1,532 patients (52.5%). CAD patients. The distribution of CAD is summarized in Figure 4. CAD was found in 9/13 AnRCA patients (69.2%; group A) and in 795/1,519 patients with normal RCA origin (52.3%; group B). The difference was not significant (p = 0.23). There was no statistically significant difference in the distribution of sex, age and cardiovascular risk factors between the two groups, nor was there a difference in the distribution of significant lesions among the 3 major coronary arteries between the two groups (Table 1). Single-vessel disease was found in 4 patients in group A; only 1 (25.0%) had the RCA affected. In group B, a total of 380 patients had single-vessel disease and 71/380 patients (18.7%) had RCA as the culprit vessel. The proportion was higher in group A compared with group B, although it was not statistically significant (p = 0.567). RCA disease patients. Among the CAD patients, RCA involvement (RCA disease) was seen in 6 patients in group A (66.7%), which was higher compared with 383 patients (48.2%) in group B, but the difference was not significant (p = 0.536). There was no significant difference in the distribution of sex and cardiovascular risk factors between the two groups (Table 2). However, there was a statistically significant difference in the age distribution. Group A was significantly younger than group B (54.8 ± 4.8 years versus 64.9 ± 10.1 years; p = 0.022), by 10 years. For the CAD patients without RCA involvement, i.e., either the left anterior descending artery or the left circumflex artery or both were involved (3 in group A, 413 in group B), the age difference was not significant (75.7 ± 6.0 years versus 64.1 ± 11.1 years; p = 0.071). Discussion AnRCA predisposes to young sudden cardiac death associated with normal coronary arteries.3–7 The AnRCA arises from the anterior part of the left coronary sinus or the aortic wall. It then turns immediately rightward in a very acute angle so that the ostium may easily kink. The coronary orifice is usually slit-like and prone to flap-like closure on exertion. The proximal part of the AnRCA is intramural, i.e., embedded within the tunica media of the aorta in some patients, and it is prone to obstruction during exercise. When the AnRCA courses between the aorta and the pulmonary trunk, it is susceptible to compression when both structures expand during exercise. All these factors impair the flow characteristics and predispose AnRCA to recurrent, episodic ischemia during exercise. In actual fact, diffuse patchy necrosis and fibrosis suggestive of repeated episodes of small infarction could be found in the myocardium in many autopsy studies.9 Victims probably die from sustained ventricular tachyarrhythmia arising from an unstable myocardial substrate. Whether this anatomical defect also predisposes to early atherosclerosis is not known. It is well documented by clinical and post mortem studies that atherosclerotic lesions do not randomly develop throughout the coronary tree, but instead localize at certain specific sites. The atherosclerotic plaque is typically distributed more in the left anterior descending artery, the more proximal segment and inner curve of a curved segment or the hips of a bifurcation point.10–12 However, it is less commonly seen in the flow-divider of a bifurcation, where there is a high flow velocity. Endothelial dysfunction is the final common pathway underlying all the cardiovascular risk factors; therefore, every part of the circulation must be equally predisposed. The local fluid mechanical factors are thought to be the determining factor for plaque distribution. High shear stress was initially thought to promote atherogenesis.13 Later studies confirmed that low shear stress is more strongly associated with atherogenesis. Friedman et al. found a negative correlation between the intimal thickness and the wall shear rate.14,15 Shear stress is proportional to the fluid velocity and viscosity. Low fluid velocity favors the formation of slow recirculation and secondary flow or eddy current. It retards the process of mass transport of atherogenic material to be removed and promotes uptake of these atherogenic materials by the vascular endothelium.16 We hypothesize that the impairment of flow characteristics in the AnRCA might predispose itself to early atherosclerosis. If this hypothesis is true, the RCA should prematurely be diseased and is the first one to be affected among the 3 major coronary arteries. It should occupy a larger proportion among the single-vessel disease group in the AnRCA patients. Nevertheless, patients may not manifest in the single-vessel disease stage; other coronary vessels might have to be concurrently narrowed before they develop symptoms. Therefore, the proportion of RCA involvement in multivessel disease should also be higher in the AnRCA patients compared with the control. In our series, the proportions of RCA involvement in the single-vessel disease or multivessel disease patients showed no significant differences. The discrepancy could be explained by the small number of AnRCA patients. The strongest evidence of this study comes from the premature development of RCA disease in the AnRCA patients. The average age of presentation is only 54.8 years old. Compared with the control population, the RCA disease patients are 10 years younger in the AnRCA group. The magnitude of AnRCA predisposition is similar to that of the gender difference, which is quite considerable. Study limitations. The major limitation of this study is the small number of diseased AnRCA patients. In addition, the selection bias and retrospective non-blinded data acquisition represented the basic fallacies of the study. Nevertheless, this study sheds some light on the possible role of AnRCA in the pathogenesis and distribution of coronary plaques. Conclusion. AnRCA is associated with early development of CAD. The affected patients are 10 years younger than patients with normal RCA origins.

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