Right coronary artery anomaly originating in the contralateral sinus of Valsalva interpreted by the angiographic rapid identification method

Background: This study aimed to determine the correspondence between the anterior dot sign at the angiography and the malignant interarterial course, defined by the gold standard coronary angiography (angioCT), in individuals with right coronary artery originating in the contralateral sinus of Valsalva. Methods: This was an observational, retrospective, and single-center study. All individuals who had both coronary angio-CT and invasive coronary angiography (ICA), and a diagnosis of right coronary artery anomaly originating in the contralateral sinus of Valsalva were screened. ICA images were retrieved and analyzed for angiographic findings, searching for the presence of the anterior dot sign, characteristic of the interarterial course. Results: Between January 2010 and April 2015, 1,410 patients who underwent angio-CT and ICA were identified. Of these, 13 patients (0.92%) had a diagnosis of right coronary anomaly originating in the contralateral sinus of Valsalva. The mean age was 59.6 ± 18.3 years, and 61.5% were males. In all 13 cases, the right coronary artery originating in the left coronary sinus showed an interarterial course (between the aorta and the pulmonary trunk) at the angio-CT. In all cases with appropriate acquisition (9/13), the ICA showed the presence of the


Introduction
Coronary artery course anomalies occur in less than 1% of the population. 1 In most cases, the presence of anomalies does not correspond to clinical manifestations or major prognostic implications. 24][5] In the United States, this condition is the second leading cause of sudden cardiac death among young athletes 6 and the leading cause among military recruits. 7Although it is difficult to estimate its exact prevalence, published data suggest that the incidence of this malignant anomaly ranges from 0.1 to 1.07%.It is estimated that the right coronary anomaly originating in the contralateral sinus of Valsalva is 6 to 10-fold more common than that of the left coronary artery, 8,9 also being more prevalent among the Japanese. 2n the past, angiographic methods were proposed to allow the diagnosis of such origin and course anomalies.The so-called dotand-eye method assumed that contrast-enhanced radiographic impressions in the right anterior oblique view ("dot" sign), when present at the anterior or posterior border of the aorta, respectively diagnosed the interarterial or retroaortic course of the coronary vessel.Similarly, the eye-shaped image could determine the pre-pulmonary and septal courses. 10owever, after the advent of coronary angiography (angio-CT), this method has become more prominent in this scenario, and it is the exam of choice for the precise definition of the origin and course of coronary anomalies. 11,12nterestingly, there are no conclusive studies in the literature to date that validate the traditional angiographic dot-eye method versus the current gold standard, coronary angio-CT.Such validation is clinically relevant, since in a significant number of cases the diagnosis of coronary anomaly occurs incidentally during cardiac catheterization (invasive coronary angiography -ICA), 2 without previous diagnosis or suspicion.The main objective of this study was to determine the correspondence between the anterior dot angiographic pattern and the interarterial course defined by coronary angiography in individuals with right coronary artery originating in the contralateral sinus of Valsalva.

Methods
This was an observational, retrospective, single-center study carried out in a high-complexity, tertiary Cardiology service.The research was based on database analysis and chart review.

Study population
The database of the Cardiology Service of Instituto do Coração of the Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo (USP) was searched with the assistance of the Medical and Hospital Information Unit, and all individuals who simultaneously had angio-CT and ICA with a diagnosis of anomalous right coronary artery originating in the contralateral sinus of Valsalva at the angio-CT were selected.

Data collection and image analysis
All reports and original images of angio-CT were retrieved and reviewed to confirm the anomalous coronary artery origin and cour se, and new reconstructions were performed when necessary.All ICA images were retrieved and analyzed to evaluate the angiographic findings.Particularly, as previously described by Serota et al., 10 angiographic projections in the right anterior oblique view were carefully analyzed to assess the presence of the anterior dot sign, characteristic of the interarterial course (Figure 1).

Results
Between January 2010 and April 2015, 1,410 patients who underwent to angio-CT and ICA were identified.The individual evaluation of each of the charts, through the electronic medical record system, resulted in the selection of 13 patients (0.92%) with a diagnosis of anomalous right coronary artery originating in the contralateral sinus of Valsalva.
Of the 13 patients that comprised the present study population, 8 (61.5%) were males and 12 (92.3%)were Caucasian.The mean age was 59.6 ± 18.3 years, ranging from 27.9 years to 95.1 years.
In all 13 cases, the right coronary artery originating in the left coronary sinus presented an interarterial course (between the aorta and the pulmonary trunk) at the angio-CT.Of these, four cases did not have ICA with ventriculography or aortography in the right anterior oblique view.In the remaining nine cases, in which such projections were systematically performed, the anterior dot was present.
Of the total number of patients, six (46.2%) remained in clinical treatment, two cases (15.4%) underwent percutaneous coronary intervention with stent implantation, one case (7.7%) was treated surgically with reimplantation of the right coronary artery, and four cases (30.8%) were submitted to surgical revascularization with grafting to the right coronary artery (Figure 2).Over two decades ago, Serota et al. 10 described the dot-and-eye method for the angiographic diagnosis of coronary anomalies, in which the anterior dot represented the impression caused by the angulated left sinus outflow of the right coronary artery, with a cour se between the aorta and the pulmonary artery.The main finding of the present study is the validation that the presence of the anterior dot sign in the coronary angiography confirms the interarterial course of the right coronary artery originating in the left sinus of Valsalva.With the implementation and increasing availability of 64-channel computed tomography, coupled with ECG-synchronized protocols and new algorithms for interactive image reconstruction, the method became the gold standard for the assessment of coronary anomalies, whose main advantages are the fact that it is not an invasive examination, having quick image acquisition, greater temporal and spatial resolution, and post-procedural 3-D reconstruction.Its disadvantages, such as the higher dose of radiation and contrast volume, have also been overcome with the development of the aforementioned techniques. 13,14n previous studies, coronary anomalies were classified as benign (80.6% in an analyzed series) or potentially serious anomalies (19.4%), including: (1) ectopic origin from the pulmonary artery, (2) ectopic origin from the contralateral sinus of Valsalva, (3) single coronary artery, and (4) large coronary fistula. 15In the present study, the study population was restricted to individuals with right coronary artery originating in the left sinus, because this anomaly is frequently associated with an interarterial course, 15,16 which consequently in creases its malignancy potential -an underestimated finding in daily clinical practice.
The present results demonstrate that this anomaly is unusual, in line with the prevalence of 0.019 to 0.92% identified in previous studies, 1,2 which, in turn, emphasizes the need to maintain a high degree of clinical suspicion for the correct angiographic detection of its morphological details.It is noteworthy that, in most of the present cases, angio-CT was performed after ICA, reflecting the lack of confidence in conventional angiography, reinforcing the need for diagnostic validation of angiographic criteria.
In theory, the coronary vessel originating in the contralateral sinus can have four distinct courses -posterior (retroaortic), septal (subpulmonary), anterior (pre-pulmonary), and interarterial -until it reaches and irrigates the territory for which it is responsible.In fact, the terminology "origin" might have been used in an inappro-priate way, since more recent studies on coronary embryology report the ingrowth theory, in which the coronary artery would develop from a tangle of epicardial vessels, and its proximal portion would fuse in the peritruncal ring. 17However, as observed in the present study, most individuals with right coronary artery originating in the left sinus have an interatrial course. 15,16The main high-risk characteristics of this type of anomalous coronary course are lateral luminal compression of the intramural portion of the anomalous vessel, coronary compression between the aorta and the pulmonary artery, slitlike orif ice, and origin with acute exit angle. 12Furthermore, these arteries have an intramural course (defined histologically by the coronary artery sharing the same media with the aorta, without adventitia interposition). 18,19Although established, the explanation of a scissors-like mechanism, created by the close proximity of the aorta and pulmonary artery, especially during exertion, is still controversial. 20everal risk stratifications have been suggested, including noninvasive assessment using provocative stress tests (myocar dial scin tigraphy, echocardiography), 21 analysis of angiotomographic anatomic criteria, 22 or even through measurements obtained by the in travascular ultrasound (IVUS) and fractional flow reserve (FFR) values associated with dobutamine infusion; 23 however, all methods present limitations.
Although the surgical treatment for the correction of coronary artery anomalies with an interarterial course is almost a consensus among specialists, 21,24 even without specific guidelines to guide such management, the best way of managing cases of malignant coronary anomalies is not well defined, especially in asymptomatic indivi duals.Among the several surgical techniques the unroofing procedure can be highlighted representing the strategy of choice when there is an intramural component of the initial course; reimplantation; coronary artery bypass grafting surgery using venous or arterial grafts; pulmonary artery translocation; and the creation of a new ostium. 15,18,25onservative treatment is recommended by some authors 26 in situations of negative results in provocative tests after drug treatment implementation (commonly with beta-blockers).More recently, percutaneous coronary intervention has been presented as an alternative technique to the limitations and risks of the surgical procedure, with good results described in the short-term follow-up. 25he use of drug-eluting stents and a careful selection of the guidecatheter, together with other devices that provide greater therapeutic support, and a IVUS-guided procedure, can contribute to maintain long-term success. 27,28

Study limitations
This was an observational, pioneering study analyzing a series of cases with a rare coronary anomaly using two methods of cardiovascular imaging.However, its retrospective nature, based on database information and patient files, as well as the small number of patients, does not allow drawing definitive and comprehensive conclusions on the subject, and further studies with a larger number of individuals are required.

Conclusions
The presence of the anterior dot sign on the coronary angiography confirmed the interarterial course of right coronary arteries originating in the contralateral sinus of Valsalva.This angiographic sign can be a valuable tool for the rapid identification of this cour se, considered to be high risk and often underestimated in daily clinical practice.

Figure 1 .
Figure 1.(A) Nonselective injection in the right coronary artery, in the right anterior oblique view, demonstrating the origin of the right coronary artery in the contralateral coronary sinus and its anterior relation with the aorta (Ao).(B) Computed angiotomography with reconstruction in the sagittal view, reproducing the anterior dot sign (arrow), defining the interarterial relation of the right coronary artery between the Ao and the pulmonary artery.(C) Computed angiotomography with 3-D reconstruction, demonstrating the origin of the right coronary artery in the left coronary sinus and interarterial course.(D) Ventriculography performed in the right anterior oblique view showing the anterior dot image in relation to the Ao (arrow).RCA: right coronary artery; PT: pulmonary trunk; LAD: left anterior descending artery.

Figure 2 .
Figure 2. Angiotomography showing a patent saphenous vein graft (SVG) in anastomosis with the right coronary artery (RCA) originating in the left sinus of Valsalva.LMCA: left main coronary artery.