X-Ray Angiography and Magnetic Resonance Imaging to Distinguish Interarterial (Full title below)

X-Ray Angiography and Magnetic Resonance Imaging to Distinguish Interarterial from Septal Courses of Anomalous Left Coronary Artery: An Ex Vivo Heart Model

ABSTRACT: Objective. We sought to demonstrate the distinguishing features between interarterial and intraseptal courses of an anomalous left coronary artery from the right sinus of Valsalva (RSV) on X-ray angiography, using an ex vivo model. Background. An anomalous left main coronary artery (LMCA) arising from the RSV can take prepulmonary, retro-aortic, interarterial (IA) or intraseptal (IS) courses, of which only the IA course is associated with sudden death. Anomalous LMCA is usually identified during catheter angiography. On X-ray angiography, IA and IS courses have common characteristics that makes their distinction challenging. We hypothesized that the cranial-caudal orientation of the vessel on X-ray angiography allows these pathways to be distinguished, and tested this hypothesis using an ex vivo heart model. Methods. Plastic tubing was inserted along the IA and IS courses in an ex vivo normal pig heart. X-ray imaging in standard views and MRI on a 3-T scanner were performed. Results. In a normally formed heart, an anomalous LMCA with IA path must take a cephalad course, superior to the pulmonary valve. Conversely, an IS vessel will pass caudally, at or below the level of the infundibular septum. These findings were demonstrated in the X-ray angiograms and confirmed by magnetic resonance imaging. Conclusions. X-ray angiography can differentiate IA and IS courses of an anomalous LMCA in the normally formed heart. This may obviate the need for further cross-sectional imaging in many cases. J INVASIVE CARDIOL 2009;21:648–652 Key words: coronary vessel anomalies, magnetic resonance imaging, computed tomography, coronary angiography The prevalence of a left main coronary artery (LMCA) arising from the right sinus of Valsalva (RSV) has been found to range from 0.017% in a series of 126,595 angiograms1 to 0.15% in a series of 1,950 angiograms.2 A left coronary artery from the RSV can take varying proximal courses: a prepulmonary (PP) course where the artery passes anterior to the right ventricular outflow tract or pulmonary trunk; a retro-aortic (RA) course, where the artery sweeps posteriorly around the aorta; an interarterial (IA) course between the aorta and pulmonary trunk (anatomically, cranial to the pulmonary valve); or an intraseptal (IS) course. Of these possible courses, the IS course is the most common, and the IA course the least common.1 The IS course may be high in the infundibular septum, or low, tunneled in the muscular septum.3–6 The differentiation of IA from IS courses is important, as IA is associated with major adverse cardiac events including sudden cardiac death, myocardial infarction or ischemia,7–13 while the PP, RA and IS courses are usually considered benign.6–16 Most anomalous coronary arteries are incidentally recognized in adults during selective coronary angiography when undergoing catheterization for suspected ischemic heart disease. Identification of PP and RA courses can be reliably made on the lateral and/or left anterior oblique (LAO) projection of X-ray angiography, possibly with the use of a pulmonary artery catheter to mark the location of the PA (Figure 1), but distinguishing IA and IS courses can be more challenging. Rules for differentiating these two courses by X-ray angiography were described by Ishikawa and Brandt3 and by Serota et al.17 Most recent literature suggests that computed tomography (CT) and/or magnetic resonance imaging (MRI) is superior or equivalent to X-ray angiography to determine the proximal course.5,18–20 However, these tests are expensive, inconvenient, entail some added patient risk, and may delay the diagnosis and treatment of a potentially dangerous condition. We hypothesized that the IA and low or high IS courses of an anomalous LMCA from the RSV can be reliably diagnosed by X-ray angiography, and used an ex vivo pig heart model with a well-defined, known anatomy to demonstrate the features of each of these courses by X-ray angiography and MRI. Materials and Methods Preparation of the ex vivo intact adult pig heart model. The pig heart model was chosen due to its similarity in size, shape and anatomic configuration to the human heart. Animal treatment was approved by the Institutional Animal Care and Use Committee and conformed to the Guide for the Care and Use of Laboratory Animals (U.S. National Institutes of Health, NIH Publication No. 85-23, revised 1996). A 0.035 inch vascular guidewire was inserted from the aorta through the the ostium of the left coronary artery and passed into the left anterior descending (LAD) coronary artery. A second wire was inserted into the right coronary artery (RCA). Implantation of 2.5 mm polyvinyl chloride (PVC) tubing was performed through an incision in the aortic wall adjacent to the RCA ostium. The first tube was placed following an IA proximal course to lie alongside the LAD in the anterior interventricular sulcus and then secured. A ventriculotomy was performed on the anterior free wall of the right ventricle surface. A second PVC tube was placed through the infundibular septum, between the aorta and the right ventricular outflow tract. In order to preserve their anatomic shapes, the aorta and pulmonary artery were supported by rigid tubular plastic scaffolds. The ventriculotomy was closed with nylon sutures. A small amount of barium sulfate paste was applied to the pulmonary sinuses of Valsalva and pulmonary valve leaflets to mark their positions for X-ray imaging. Following performance of X-ray angiography and MRI (see below), the IS tube was removed and replaced with another tube in the low septal position. The model now had IA and low septal tubing courses and was imaged again with both modalities. Conventional X-ray angiography. This was performed using an adult biplane conventional angiography unit (Inturis, Philips Medical Systems, Best, The Netherlands). The initial tube settings were 65 kV potential and 80 mA current. The heart was placed in a foam bed on the table to emulate anatomical positioning within the human body. Prior to performance of each imaging examination, the proper anatomic configuration was confirmed by an experienced cardiac pathologist (S.H.L.). The pig heart was imaged in all standard views routinely used during adult coronary angiography. No X-ray contrast material was used in the tubing, as the PVC had sufficient X-ray absorption to provide adequate image contrast. In addition, straight views with no cranial or caudal angulation were obtained in the 30º right anterior oblique (RAO), antero-posterior (AP), 60º left anterior oblique (LAO), and left lateral projections. These were repeated after each change in the tube positioning, as described above. Magnetic resonance imaging. MRI was performed on a 3 Tesla scanner (Intera, Philips Medical Systems) using a 6-element phased-array coil. The heart was placed in a water-filled pan, supported by the foam bed in the proper anatomic position. The PVC tubes were filled with copper sulfate solution (3.3 mM) as contrast for imaging. The scan was performed using a gradient echo sequence (3-D TFE) designed for coronary artery imaging (scan details: repetition time 10 ms, echo time 3.4 ms, flip angle 120º, bandwidth 217 Hz per pixel; SENSE factor 2; T2 prep; fat saturation). The slice thickness was 3.0 mm with an overlap of 1.5 mm; the field of view was 16 cm with acquired matrix size 384 x 270 pixels. The reconstructed resolution was 0.31 x 0.31 x 1.5 mm. The raw data were reformatted using a curved planar method.21 Results In the normal human heart, the pulmonary valve lies cephalad and to the left of the aortic valve.The infundibular septum separates the aortic and pulmonary valves, and inferiorly becomes continuous with the interventricular portion of the membranous septum (Figure 2C). The right and left sinuses of Valsalva face the pulmonary valve, and RSV is caudal to the left sinus of Valsalva (LSV) (Figure 2A). Therefore, a LMCA arising from the RSV with an IA course must ascend cephalad to the pulmonary valve to pass between the aorta and the pulmonary trunk so that the proximal vessel will point cranially and posteriorly. Conversely, a LMCA from the RSV with an IS course must take a horizontal (or even caudal) and posterior course to lie in the interventricular septum (either high in the infundibular septum, or lower in the muscular septum) (Figures 3 and 4). These features are demonstrated in the straight (without cranial or caudal angulation) AP or 30º RAO view on X-ray angiography (Figures 3A and 4A). The straight 60º LAO view shows a shallow posterior course of the most proximal segment in both the IA and IS courses (Figures 3B and 4B). Figures 3C and 4C show the corresponding curved planar reconstructed images from MRI. Figures 3D and 3E are example RAO angiograms in a patient with an IA LMCA (Figure 3D; pathway confirmed by cardiac MRI) and a patient with a high septal LMCA (Figure 3E; confirmed by cardiac MRI). An IS vessel also frequently gives off a septal perforator from the proximal left main trunk (labeled “S” in the figure), another clue to its septal location.3 Figure 4 shows RAO views of the same patient as in Figure 3D, with the IA pathway (Figure 4D) and another patient with a low septal course of a LAD (confirmed by MRI) arising anomalously from the RSV (Figure 4E). In Figure 4E the vessel is seen to dip down in the initial portion, forming a “V” shape and also seen to give septal perforator branch much like that of the high infundibular septal vessel shown in Figure 3E. Figure 5 shows the IA and the high septal course in the RAO cranial (Figure 5A), RAO caudal (Figure 5B), LAO cranial (Figure 5C) and the LAO caudal (Figure 5D) projections on X-ray images. The addition of cranial or caudal angulation makes the identification of the initial pathway more difficult. Figure 6 shows a simplified illustration of the relevant structures in RAO and LAO angiograms, with interarterial, high septal and low septal courses on cross section (A, B and C) at the indicated levels. Discussion Evidence shows that an IA course is associated with adverse cardiac events, in contradistinction to other possible courses (IS, RA or PP). Because the PP and RA courses of an anomalous LMCA are readily differentiated from the other pathways by the LAO or lateral X-ray angiographic projection (Figure 1), we focused our work on the more challenging distinction between the IS and IA pathways. Using an ex-vivo heart model with known anatomy of implanted tubes, we demonstrate that X-ray angiography with RAO, LAO, AP and lateral views, without any cranial or caudal angulations, is convincingly able to differentiate the IA and IS courses of the anomalous LMCA arising from the right coronary cusp. Adding cranial or caudal angulations will make differentiating these courses more difficult (Figure 5). This work represents the first combined X-ray angiographic and MRI study of a realistic anatomic model of an anomalous left coronary artery. CT or MRI, often considered superior to X-ray angiography for determining the vessel course, may yield the erroneous diagnosis if the pulmonary valve plane is not well visualized on the images.22 While it is possible to examine the MRI or CT images for the presence of muscle (suggesting an intramyocardially tunneled vessel) or fat (suggesting an interarterial course) surrounding the vessel segment, this method is subject to uncertainty, as the appearance of muscle or fat around the vessel may depend on technique. Therefore, we favor using the anatomic method described here to determine the proximal course of the vessel. On the straight AP or RAO view, a cranial proximal course is suggestive of either a PP or IA course while a caudal proximal course is suggestive of an IS or retro-aortic course, and on the straight LAO or left lateral view, an anterior proximal direction is seen in a vessel with a PP course, while a posterior proximal course suggests a RA, IA or IS course. MRI or CT may be useful in certain difficult cases with uncertain courses (e.g., when the anomalous vessel cannot be selectively catheterized) or in patients with congenital malformations of the cardiac chambers. Ironically, the availability of cardiac CT or MRI probably has an undesirable practical influence on angiographic performance, since an angiographer may not be as diligent in attempting to identify the vessel if the patient can be referred for another imaging study. Differentiating the true IA from the IS course of the anomalous LMCA from the RSV has important clinical implications since the IA path is considered “malignant.”7–13 The IS course has been suggested to portend a more benign prognosis, and continued observation may be warranted.6,23 To our knowledge, only 1 case of sudden death attributable to cardiac causes in a patient with an anomalous LMCA with a low septal course has been reported.9 The prognosis of a high septal vessel (Figure 2), however, is less clear. There is also considerable confusion in the literature regarding the anatomic definition of the terms “interarterial” and “septal” for the courses, with the recent literature considering only intramyocardial tunneling as “septal” and the infundibular septal and true interarterial courses grouped together as “interarterial.”5,18,19 We believe that a precise anatomic description of the path is important: unless an accurate distinction is made, we may never know the relationship between these paths and adverse cardiac events. Conclusions Using an ex vivo heart model, X-ray angiography was able to differentiate an IA course from an IS course of an anomalous LMCA from the RSV. The straight AP or RAO and straight LAO angiographic projections were best for differentiating these courses. Similar anatomic information was obtained by MRI using curved reformatting in the model. Coronary MR or CT angiography is not imperative to determine the proximal vessel course in a normally formed heart, but may be useful in select cases if uncertainty remains after X-ray angiography. From the §Division of Cardiovascular Disease, Department of Medicine, £Department of Pathology, ∞Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama. *These authors contributed equally to this work. The authors report no conflicts of interest regarding the content herein. Manuscript submitted May 18, 2009, provisional acceptance given July 24, 2009, final version accepted August 31, 2009. Address for correspondence: Steven G. Lloyd, MD, PhD, D-101 Cardiovascular MRI, 1808 7th Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294. E-mail: sglloyd@uab.edu

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